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Slide 1 - 2010 ACR/EULAR Classification Criteria for Rheumatoid Arthritis
Slide 2 - 2010 ACR/EULAR Classification Criteria for Rheumatoid Arthritis Published in the September 2010 Issues of A&R and ARD
Slide 3 - 2010 ACR/EULAR Classification Criteria for Rheumatoid Arthritis Published in the September 2010 Issues of A&R and ARD Phases of the Project Phase 1 Data analysis Phase 2 Consensus process Phase 3 Integration of 1 and 2 Predictors of MTX initiation Final Criteria Determinants of high probability of RA Increase feasibility
Slide 4 - 2010 ACR/EULAR Classification Criteria for Rheumatoid Arthritis Published in the September 2010 Issues of A&R and ARD Phases of the Project Phase 1 Data analysis Phase 2 Consensus process Phase 3 Integration of 1 and 2 Predictors of MTX initiation Final Criteria Determinants of high probability of RA Increase feasibility Phase 1 Data Driven Approach
Slide 5 - 2010 ACR/EULAR Classification Criteria for Rheumatoid Arthritis Published in the September 2010 Issues of A&R and ARD Phases of the Project Phase 1 Data analysis Phase 2 Consensus process Phase 3 Integration of 1 and 2 Predictors of MTX initiation Final Criteria Determinants of high probability of RA Increase feasibility Phase 1 Data Driven Approach Phase 1: Patients and Methods Patients – EARLY ARTHRITIS COHORTS 3115 patients from 9 cohorts Inflammatory arthritis (no other definite diagnosis) of <3 years No previous DMARD/MTX treatment Methods – PREDICTORS OF MTX TREATMENT Step 1: Univariate regression analysis of all possible variables Step 2: Principal component analysis: identify themes Step 3: Multivariate regression analysis with all relevant themes
Slide 6 - 2010 ACR/EULAR Classification Criteria for Rheumatoid Arthritis Published in the September 2010 Issues of A&R and ARD Phases of the Project Phase 1 Data analysis Phase 2 Consensus process Phase 3 Integration of 1 and 2 Predictors of MTX initiation Final Criteria Determinants of high probability of RA Increase feasibility Phase 1 Data Driven Approach Phase 1: Patients and Methods Patients – EARLY ARTHRITIS COHORTS 3115 patients from 9 cohorts Inflammatory arthritis (no other definite diagnosis) of <3 years No previous DMARD/MTX treatment Methods – PREDICTORS OF MTX TREATMENT Step 1: Univariate regression analysis of all possible variables Step 2: Principal component analysis: identify themes Step 3: Multivariate regression analysis with all relevant themes Phase 1: Three Analytic Steps Univariate Regression Analysis Identify significant variables at baseline Gold standard: MTX treatment at one year STEP 1
Slide 7 - 2010 ACR/EULAR Classification Criteria for Rheumatoid Arthritis Published in the September 2010 Issues of A&R and ARD Phases of the Project Phase 1 Data analysis Phase 2 Consensus process Phase 3 Integration of 1 and 2 Predictors of MTX initiation Final Criteria Determinants of high probability of RA Increase feasibility Phase 1 Data Driven Approach Phase 1: Patients and Methods Patients – EARLY ARTHRITIS COHORTS 3115 patients from 9 cohorts Inflammatory arthritis (no other definite diagnosis) of <3 years No previous DMARD/MTX treatment Methods – PREDICTORS OF MTX TREATMENT Step 1: Univariate regression analysis of all possible variables Step 2: Principal component analysis: identify themes Step 3: Multivariate regression analysis with all relevant themes Phase 1: Three Analytic Steps Univariate Regression Analysis Identify significant variables at baseline Gold standard: MTX treatment at one year STEP 1 STEPS 1 and 2: Predictors of MTX initiation Loadings: 0 – 0.199 0.2 – 0.399 0.4 – 0.599 0.6 – 0.799 0.8 – 1
Slide 8 - 2010 ACR/EULAR Classification Criteria for Rheumatoid Arthritis Published in the September 2010 Issues of A&R and ARD Phases of the Project Phase 1 Data analysis Phase 2 Consensus process Phase 3 Integration of 1 and 2 Predictors of MTX initiation Final Criteria Determinants of high probability of RA Increase feasibility Phase 1 Data Driven Approach Phase 1: Patients and Methods Patients – EARLY ARTHRITIS COHORTS 3115 patients from 9 cohorts Inflammatory arthritis (no other definite diagnosis) of <3 years No previous DMARD/MTX treatment Methods – PREDICTORS OF MTX TREATMENT Step 1: Univariate regression analysis of all possible variables Step 2: Principal component analysis: identify themes Step 3: Multivariate regression analysis with all relevant themes Phase 1: Three Analytic Steps Univariate Regression Analysis Identify significant variables at baseline Gold standard: MTX treatment at one year STEP 1 STEPS 1 and 2: Predictors of MTX initiation Loadings: 0 – 0.199 0.2 – 0.399 0.4 – 0.599 0.6 – 0.799 0.8 – 1 STEP 2: Relevant Themes to Predict MTX Treatment
Slide 9 - 2010 ACR/EULAR Classification Criteria for Rheumatoid Arthritis Published in the September 2010 Issues of A&R and ARD Phases of the Project Phase 1 Data analysis Phase 2 Consensus process Phase 3 Integration of 1 and 2 Predictors of MTX initiation Final Criteria Determinants of high probability of RA Increase feasibility Phase 1 Data Driven Approach Phase 1: Patients and Methods Patients – EARLY ARTHRITIS COHORTS 3115 patients from 9 cohorts Inflammatory arthritis (no other definite diagnosis) of <3 years No previous DMARD/MTX treatment Methods – PREDICTORS OF MTX TREATMENT Step 1: Univariate regression analysis of all possible variables Step 2: Principal component analysis: identify themes Step 3: Multivariate regression analysis with all relevant themes Phase 1: Three Analytic Steps Univariate Regression Analysis Identify significant variables at baseline Gold standard: MTX treatment at one year STEP 1 STEPS 1 and 2: Predictors of MTX initiation Loadings: 0 – 0.199 0.2 – 0.399 0.4 – 0.599 0.6 – 0.799 0.8 – 1 STEP 2: Relevant Themes to Predict MTX Treatment Phase 1: Results
Slide 10 - 2010 ACR/EULAR Classification Criteria for Rheumatoid Arthritis Published in the September 2010 Issues of A&R and ARD Phases of the Project Phase 1 Data analysis Phase 2 Consensus process Phase 3 Integration of 1 and 2 Predictors of MTX initiation Final Criteria Determinants of high probability of RA Increase feasibility Phase 1 Data Driven Approach Phase 1: Patients and Methods Patients – EARLY ARTHRITIS COHORTS 3115 patients from 9 cohorts Inflammatory arthritis (no other definite diagnosis) of <3 years No previous DMARD/MTX treatment Methods – PREDICTORS OF MTX TREATMENT Step 1: Univariate regression analysis of all possible variables Step 2: Principal component analysis: identify themes Step 3: Multivariate regression analysis with all relevant themes Phase 1: Three Analytic Steps Univariate Regression Analysis Identify significant variables at baseline Gold standard: MTX treatment at one year STEP 1 STEPS 1 and 2: Predictors of MTX initiation Loadings: 0 – 0.199 0.2 – 0.399 0.4 – 0.599 0.6 – 0.799 0.8 – 1 STEP 2: Relevant Themes to Predict MTX Treatment Phase 1: Results Phase 1: Conclusion Swelling of small joint regions (PIP, MCP, wrist) has independent effect Tenderness might be also be considered as “joint involvement” Symmetrical involvement does not seem to have a significant incremental effect over unilateral involvement Abnormal acute phase response has a considerable effect Serology has a considerable effect, and shows a “dose-response” relationship of titres
Slide 11 - 2010 ACR/EULAR Classification Criteria for Rheumatoid Arthritis Published in the September 2010 Issues of A&R and ARD Phases of the Project Phase 1 Data analysis Phase 2 Consensus process Phase 3 Integration of 1 and 2 Predictors of MTX initiation Final Criteria Determinants of high probability of RA Increase feasibility Phase 1 Data Driven Approach Phase 1: Patients and Methods Patients – EARLY ARTHRITIS COHORTS 3115 patients from 9 cohorts Inflammatory arthritis (no other definite diagnosis) of <3 years No previous DMARD/MTX treatment Methods – PREDICTORS OF MTX TREATMENT Step 1: Univariate regression analysis of all possible variables Step 2: Principal component analysis: identify themes Step 3: Multivariate regression analysis with all relevant themes Phase 1: Three Analytic Steps Univariate Regression Analysis Identify significant variables at baseline Gold standard: MTX treatment at one year STEP 1 STEPS 1 and 2: Predictors of MTX initiation Loadings: 0 – 0.199 0.2 – 0.399 0.4 – 0.599 0.6 – 0.799 0.8 – 1 STEP 2: Relevant Themes to Predict MTX Treatment Phase 1: Results Phase 1: Conclusion Swelling of small joint regions (PIP, MCP, wrist) has independent effect Tenderness might be also be considered as “joint involvement” Symmetrical involvement does not seem to have a significant incremental effect over unilateral involvement Abnormal acute phase response has a considerable effect Serology has a considerable effect, and shows a “dose-response” relationship of titres Phases of the Project Phase 1 Data analysis Phase 2 Consensus process Phase 3 Integration of 1 and 2 Predictors of MTX initiation Final Criteria Determinants of high probability of RA Increase feasibility
Slide 12 - 2010 ACR/EULAR Classification Criteria for Rheumatoid Arthritis Published in the September 2010 Issues of A&R and ARD Phases of the Project Phase 1 Data analysis Phase 2 Consensus process Phase 3 Integration of 1 and 2 Predictors of MTX initiation Final Criteria Determinants of high probability of RA Increase feasibility Phase 1 Data Driven Approach Phase 1: Patients and Methods Patients – EARLY ARTHRITIS COHORTS 3115 patients from 9 cohorts Inflammatory arthritis (no other definite diagnosis) of <3 years No previous DMARD/MTX treatment Methods – PREDICTORS OF MTX TREATMENT Step 1: Univariate regression analysis of all possible variables Step 2: Principal component analysis: identify themes Step 3: Multivariate regression analysis with all relevant themes Phase 1: Three Analytic Steps Univariate Regression Analysis Identify significant variables at baseline Gold standard: MTX treatment at one year STEP 1 STEPS 1 and 2: Predictors of MTX initiation Loadings: 0 – 0.199 0.2 – 0.399 0.4 – 0.599 0.6 – 0.799 0.8 – 1 STEP 2: Relevant Themes to Predict MTX Treatment Phase 1: Results Phase 1: Conclusion Swelling of small joint regions (PIP, MCP, wrist) has independent effect Tenderness might be also be considered as “joint involvement” Symmetrical involvement does not seem to have a significant incremental effect over unilateral involvement Abnormal acute phase response has a considerable effect Serology has a considerable effect, and shows a “dose-response” relationship of titres Phases of the Project Phase 1 Data analysis Phase 2 Consensus process Phase 3 Integration of 1 and 2 Predictors of MTX initiation Final Criteria Determinants of high probability of RA Increase feasibility Phase 2 Consensus Approach
Slide 13 - 2010 ACR/EULAR Classification Criteria for Rheumatoid Arthritis Published in the September 2010 Issues of A&R and ARD Phases of the Project Phase 1 Data analysis Phase 2 Consensus process Phase 3 Integration of 1 and 2 Predictors of MTX initiation Final Criteria Determinants of high probability of RA Increase feasibility Phase 1 Data Driven Approach Phase 1: Patients and Methods Patients – EARLY ARTHRITIS COHORTS 3115 patients from 9 cohorts Inflammatory arthritis (no other definite diagnosis) of <3 years No previous DMARD/MTX treatment Methods – PREDICTORS OF MTX TREATMENT Step 1: Univariate regression analysis of all possible variables Step 2: Principal component analysis: identify themes Step 3: Multivariate regression analysis with all relevant themes Phase 1: Three Analytic Steps Univariate Regression Analysis Identify significant variables at baseline Gold standard: MTX treatment at one year STEP 1 STEPS 1 and 2: Predictors of MTX initiation Loadings: 0 – 0.199 0.2 – 0.399 0.4 – 0.599 0.6 – 0.799 0.8 – 1 STEP 2: Relevant Themes to Predict MTX Treatment Phase 1: Results Phase 1: Conclusion Swelling of small joint regions (PIP, MCP, wrist) has independent effect Tenderness might be also be considered as “joint involvement” Symmetrical involvement does not seem to have a significant incremental effect over unilateral involvement Abnormal acute phase response has a considerable effect Serology has a considerable effect, and shows a “dose-response” relationship of titres Phases of the Project Phase 1 Data analysis Phase 2 Consensus process Phase 3 Integration of 1 and 2 Predictors of MTX initiation Final Criteria Determinants of high probability of RA Increase feasibility Phase 2 Consensus Approach Phase 2: Methods Ranking of patient profiles by experts for their probability to develop RA Evidence based discussion on discrepancies in the ranking Specifying target population Developing positive and negative determinants for risk of RA (informed by Phase 1 data) Grouping these determinants into domains and categories Weighting of each category using decision analytic software
Slide 14 - 2010 ACR/EULAR Classification Criteria for Rheumatoid Arthritis Published in the September 2010 Issues of A&R and ARD Phases of the Project Phase 1 Data analysis Phase 2 Consensus process Phase 3 Integration of 1 and 2 Predictors of MTX initiation Final Criteria Determinants of high probability of RA Increase feasibility Phase 1 Data Driven Approach Phase 1: Patients and Methods Patients – EARLY ARTHRITIS COHORTS 3115 patients from 9 cohorts Inflammatory arthritis (no other definite diagnosis) of <3 years No previous DMARD/MTX treatment Methods – PREDICTORS OF MTX TREATMENT Step 1: Univariate regression analysis of all possible variables Step 2: Principal component analysis: identify themes Step 3: Multivariate regression analysis with all relevant themes Phase 1: Three Analytic Steps Univariate Regression Analysis Identify significant variables at baseline Gold standard: MTX treatment at one year STEP 1 STEPS 1 and 2: Predictors of MTX initiation Loadings: 0 – 0.199 0.2 – 0.399 0.4 – 0.599 0.6 – 0.799 0.8 – 1 STEP 2: Relevant Themes to Predict MTX Treatment Phase 1: Results Phase 1: Conclusion Swelling of small joint regions (PIP, MCP, wrist) has independent effect Tenderness might be also be considered as “joint involvement” Symmetrical involvement does not seem to have a significant incremental effect over unilateral involvement Abnormal acute phase response has a considerable effect Serology has a considerable effect, and shows a “dose-response” relationship of titres Phases of the Project Phase 1 Data analysis Phase 2 Consensus process Phase 3 Integration of 1 and 2 Predictors of MTX initiation Final Criteria Determinants of high probability of RA Increase feasibility Phase 2 Consensus Approach Phase 2: Methods Ranking of patient profiles by experts for their probability to develop RA Evidence based discussion on discrepancies in the ranking Specifying target population Developing positive and negative determinants for risk of RA (informed by Phase 1 data) Grouping these determinants into domains and categories Weighting of each category using decision analytic software Phase 2: Overview Expert panel
Slide 15 - 2010 ACR/EULAR Classification Criteria for Rheumatoid Arthritis Published in the September 2010 Issues of A&R and ARD Phases of the Project Phase 1 Data analysis Phase 2 Consensus process Phase 3 Integration of 1 and 2 Predictors of MTX initiation Final Criteria Determinants of high probability of RA Increase feasibility Phase 1 Data Driven Approach Phase 1: Patients and Methods Patients – EARLY ARTHRITIS COHORTS 3115 patients from 9 cohorts Inflammatory arthritis (no other definite diagnosis) of <3 years No previous DMARD/MTX treatment Methods – PREDICTORS OF MTX TREATMENT Step 1: Univariate regression analysis of all possible variables Step 2: Principal component analysis: identify themes Step 3: Multivariate regression analysis with all relevant themes Phase 1: Three Analytic Steps Univariate Regression Analysis Identify significant variables at baseline Gold standard: MTX treatment at one year STEP 1 STEPS 1 and 2: Predictors of MTX initiation Loadings: 0 – 0.199 0.2 – 0.399 0.4 – 0.599 0.6 – 0.799 0.8 – 1 STEP 2: Relevant Themes to Predict MTX Treatment Phase 1: Results Phase 1: Conclusion Swelling of small joint regions (PIP, MCP, wrist) has independent effect Tenderness might be also be considered as “joint involvement” Symmetrical involvement does not seem to have a significant incremental effect over unilateral involvement Abnormal acute phase response has a considerable effect Serology has a considerable effect, and shows a “dose-response” relationship of titres Phases of the Project Phase 1 Data analysis Phase 2 Consensus process Phase 3 Integration of 1 and 2 Predictors of MTX initiation Final Criteria Determinants of high probability of RA Increase feasibility Phase 2 Consensus Approach Phase 2: Methods Ranking of patient profiles by experts for their probability to develop RA Evidence based discussion on discrepancies in the ranking Specifying target population Developing positive and negative determinants for risk of RA (informed by Phase 1 data) Grouping these determinants into domains and categories Weighting of each category using decision analytic software Phase 2: Overview Expert panel Phase 2: Overview Expert panel Submit case scenarios of early undifferentiated inflammatory arthritis
Slide 16 - 2010 ACR/EULAR Classification Criteria for Rheumatoid Arthritis Published in the September 2010 Issues of A&R and ARD Phases of the Project Phase 1 Data analysis Phase 2 Consensus process Phase 3 Integration of 1 and 2 Predictors of MTX initiation Final Criteria Determinants of high probability of RA Increase feasibility Phase 1 Data Driven Approach Phase 1: Patients and Methods Patients – EARLY ARTHRITIS COHORTS 3115 patients from 9 cohorts Inflammatory arthritis (no other definite diagnosis) of <3 years No previous DMARD/MTX treatment Methods – PREDICTORS OF MTX TREATMENT Step 1: Univariate regression analysis of all possible variables Step 2: Principal component analysis: identify themes Step 3: Multivariate regression analysis with all relevant themes Phase 1: Three Analytic Steps Univariate Regression Analysis Identify significant variables at baseline Gold standard: MTX treatment at one year STEP 1 STEPS 1 and 2: Predictors of MTX initiation Loadings: 0 – 0.199 0.2 – 0.399 0.4 – 0.599 0.6 – 0.799 0.8 – 1 STEP 2: Relevant Themes to Predict MTX Treatment Phase 1: Results Phase 1: Conclusion Swelling of small joint regions (PIP, MCP, wrist) has independent effect Tenderness might be also be considered as “joint involvement” Symmetrical involvement does not seem to have a significant incremental effect over unilateral involvement Abnormal acute phase response has a considerable effect Serology has a considerable effect, and shows a “dose-response” relationship of titres Phases of the Project Phase 1 Data analysis Phase 2 Consensus process Phase 3 Integration of 1 and 2 Predictors of MTX initiation Final Criteria Determinants of high probability of RA Increase feasibility Phase 2 Consensus Approach Phase 2: Methods Ranking of patient profiles by experts for their probability to develop RA Evidence based discussion on discrepancies in the ranking Specifying target population Developing positive and negative determinants for risk of RA (informed by Phase 1 data) Grouping these determinants into domains and categories Weighting of each category using decision analytic software Phase 2: Overview Expert panel Phase 2: Overview Expert panel Submit case scenarios of early undifferentiated inflammatory arthritis Phase 2: Overview Expert panel Specify target population
Slide 17 - 2010 ACR/EULAR Classification Criteria for Rheumatoid Arthritis Published in the September 2010 Issues of A&R and ARD Phases of the Project Phase 1 Data analysis Phase 2 Consensus process Phase 3 Integration of 1 and 2 Predictors of MTX initiation Final Criteria Determinants of high probability of RA Increase feasibility Phase 1 Data Driven Approach Phase 1: Patients and Methods Patients – EARLY ARTHRITIS COHORTS 3115 patients from 9 cohorts Inflammatory arthritis (no other definite diagnosis) of <3 years No previous DMARD/MTX treatment Methods – PREDICTORS OF MTX TREATMENT Step 1: Univariate regression analysis of all possible variables Step 2: Principal component analysis: identify themes Step 3: Multivariate regression analysis with all relevant themes Phase 1: Three Analytic Steps Univariate Regression Analysis Identify significant variables at baseline Gold standard: MTX treatment at one year STEP 1 STEPS 1 and 2: Predictors of MTX initiation Loadings: 0 – 0.199 0.2 – 0.399 0.4 – 0.599 0.6 – 0.799 0.8 – 1 STEP 2: Relevant Themes to Predict MTX Treatment Phase 1: Results Phase 1: Conclusion Swelling of small joint regions (PIP, MCP, wrist) has independent effect Tenderness might be also be considered as “joint involvement” Symmetrical involvement does not seem to have a significant incremental effect over unilateral involvement Abnormal acute phase response has a considerable effect Serology has a considerable effect, and shows a “dose-response” relationship of titres Phases of the Project Phase 1 Data analysis Phase 2 Consensus process Phase 3 Integration of 1 and 2 Predictors of MTX initiation Final Criteria Determinants of high probability of RA Increase feasibility Phase 2 Consensus Approach Phase 2: Methods Ranking of patient profiles by experts for their probability to develop RA Evidence based discussion on discrepancies in the ranking Specifying target population Developing positive and negative determinants for risk of RA (informed by Phase 1 data) Grouping these determinants into domains and categories Weighting of each category using decision analytic software Phase 2: Overview Expert panel Phase 2: Overview Expert panel Submit case scenarios of early undifferentiated inflammatory arthritis Phase 2: Overview Expert panel Specify target population Phase 2: Overview Expert panel Specify target population Positive factors + Negative factors - Discussion on reasons for discordance among physicians
Slide 18 - 2010 ACR/EULAR Classification Criteria for Rheumatoid Arthritis Published in the September 2010 Issues of A&R and ARD Phases of the Project Phase 1 Data analysis Phase 2 Consensus process Phase 3 Integration of 1 and 2 Predictors of MTX initiation Final Criteria Determinants of high probability of RA Increase feasibility Phase 1 Data Driven Approach Phase 1: Patients and Methods Patients – EARLY ARTHRITIS COHORTS 3115 patients from 9 cohorts Inflammatory arthritis (no other definite diagnosis) of <3 years No previous DMARD/MTX treatment Methods – PREDICTORS OF MTX TREATMENT Step 1: Univariate regression analysis of all possible variables Step 2: Principal component analysis: identify themes Step 3: Multivariate regression analysis with all relevant themes Phase 1: Three Analytic Steps Univariate Regression Analysis Identify significant variables at baseline Gold standard: MTX treatment at one year STEP 1 STEPS 1 and 2: Predictors of MTX initiation Loadings: 0 – 0.199 0.2 – 0.399 0.4 – 0.599 0.6 – 0.799 0.8 – 1 STEP 2: Relevant Themes to Predict MTX Treatment Phase 1: Results Phase 1: Conclusion Swelling of small joint regions (PIP, MCP, wrist) has independent effect Tenderness might be also be considered as “joint involvement” Symmetrical involvement does not seem to have a significant incremental effect over unilateral involvement Abnormal acute phase response has a considerable effect Serology has a considerable effect, and shows a “dose-response” relationship of titres Phases of the Project Phase 1 Data analysis Phase 2 Consensus process Phase 3 Integration of 1 and 2 Predictors of MTX initiation Final Criteria Determinants of high probability of RA Increase feasibility Phase 2 Consensus Approach Phase 2: Methods Ranking of patient profiles by experts for their probability to develop RA Evidence based discussion on discrepancies in the ranking Specifying target population Developing positive and negative determinants for risk of RA (informed by Phase 1 data) Grouping these determinants into domains and categories Weighting of each category using decision analytic software Phase 2: Overview Expert panel Phase 2: Overview Expert panel Submit case scenarios of early undifferentiated inflammatory arthritis Phase 2: Overview Expert panel Specify target population Phase 2: Overview Expert panel Specify target population Positive factors + Negative factors - Discussion on reasons for discordance among physicians Phase 2: Overview Specify target population Positive factors + Negative factors - Discussion on reasons for discordance among physicians
Slide 19 - 2010 ACR/EULAR Classification Criteria for Rheumatoid Arthritis Published in the September 2010 Issues of A&R and ARD Phases of the Project Phase 1 Data analysis Phase 2 Consensus process Phase 3 Integration of 1 and 2 Predictors of MTX initiation Final Criteria Determinants of high probability of RA Increase feasibility Phase 1 Data Driven Approach Phase 1: Patients and Methods Patients – EARLY ARTHRITIS COHORTS 3115 patients from 9 cohorts Inflammatory arthritis (no other definite diagnosis) of <3 years No previous DMARD/MTX treatment Methods – PREDICTORS OF MTX TREATMENT Step 1: Univariate regression analysis of all possible variables Step 2: Principal component analysis: identify themes Step 3: Multivariate regression analysis with all relevant themes Phase 1: Three Analytic Steps Univariate Regression Analysis Identify significant variables at baseline Gold standard: MTX treatment at one year STEP 1 STEPS 1 and 2: Predictors of MTX initiation Loadings: 0 – 0.199 0.2 – 0.399 0.4 – 0.599 0.6 – 0.799 0.8 – 1 STEP 2: Relevant Themes to Predict MTX Treatment Phase 1: Results Phase 1: Conclusion Swelling of small joint regions (PIP, MCP, wrist) has independent effect Tenderness might be also be considered as “joint involvement” Symmetrical involvement does not seem to have a significant incremental effect over unilateral involvement Abnormal acute phase response has a considerable effect Serology has a considerable effect, and shows a “dose-response” relationship of titres Phases of the Project Phase 1 Data analysis Phase 2 Consensus process Phase 3 Integration of 1 and 2 Predictors of MTX initiation Final Criteria Determinants of high probability of RA Increase feasibility Phase 2 Consensus Approach Phase 2: Methods Ranking of patient profiles by experts for their probability to develop RA Evidence based discussion on discrepancies in the ranking Specifying target population Developing positive and negative determinants for risk of RA (informed by Phase 1 data) Grouping these determinants into domains and categories Weighting of each category using decision analytic software Phase 2: Overview Expert panel Phase 2: Overview Expert panel Submit case scenarios of early undifferentiated inflammatory arthritis Phase 2: Overview Expert panel Specify target population Phase 2: Overview Expert panel Specify target population Positive factors + Negative factors - Discussion on reasons for discordance among physicians Phase 2: Overview Specify target population Positive factors + Negative factors - Discussion on reasons for discordance among physicians Phase 2: Results
Slide 20 - 2010 ACR/EULAR Classification Criteria for Rheumatoid Arthritis Published in the September 2010 Issues of A&R and ARD Phases of the Project Phase 1 Data analysis Phase 2 Consensus process Phase 3 Integration of 1 and 2 Predictors of MTX initiation Final Criteria Determinants of high probability of RA Increase feasibility Phase 1 Data Driven Approach Phase 1: Patients and Methods Patients – EARLY ARTHRITIS COHORTS 3115 patients from 9 cohorts Inflammatory arthritis (no other definite diagnosis) of <3 years No previous DMARD/MTX treatment Methods – PREDICTORS OF MTX TREATMENT Step 1: Univariate regression analysis of all possible variables Step 2: Principal component analysis: identify themes Step 3: Multivariate regression analysis with all relevant themes Phase 1: Three Analytic Steps Univariate Regression Analysis Identify significant variables at baseline Gold standard: MTX treatment at one year STEP 1 STEPS 1 and 2: Predictors of MTX initiation Loadings: 0 – 0.199 0.2 – 0.399 0.4 – 0.599 0.6 – 0.799 0.8 – 1 STEP 2: Relevant Themes to Predict MTX Treatment Phase 1: Results Phase 1: Conclusion Swelling of small joint regions (PIP, MCP, wrist) has independent effect Tenderness might be also be considered as “joint involvement” Symmetrical involvement does not seem to have a significant incremental effect over unilateral involvement Abnormal acute phase response has a considerable effect Serology has a considerable effect, and shows a “dose-response” relationship of titres Phases of the Project Phase 1 Data analysis Phase 2 Consensus process Phase 3 Integration of 1 and 2 Predictors of MTX initiation Final Criteria Determinants of high probability of RA Increase feasibility Phase 2 Consensus Approach Phase 2: Methods Ranking of patient profiles by experts for their probability to develop RA Evidence based discussion on discrepancies in the ranking Specifying target population Developing positive and negative determinants for risk of RA (informed by Phase 1 data) Grouping these determinants into domains and categories Weighting of each category using decision analytic software Phase 2: Overview Expert panel Phase 2: Overview Expert panel Submit case scenarios of early undifferentiated inflammatory arthritis Phase 2: Overview Expert panel Specify target population Phase 2: Overview Expert panel Specify target population Positive factors + Negative factors - Discussion on reasons for discordance among physicians Phase 2: Overview Specify target population Positive factors + Negative factors - Discussion on reasons for discordance among physicians Phase 2: Results Phases of the Project Phase 1 Data analysis Phase 2 Consensus process Phase 3 Integration of 1 and 2 Predictors of MTX initiation Final Criteria Determinants of high probability of RA Increase feasibility
Slide 21 - 2010 ACR/EULAR Classification Criteria for Rheumatoid Arthritis Published in the September 2010 Issues of A&R and ARD Phases of the Project Phase 1 Data analysis Phase 2 Consensus process Phase 3 Integration of 1 and 2 Predictors of MTX initiation Final Criteria Determinants of high probability of RA Increase feasibility Phase 1 Data Driven Approach Phase 1: Patients and Methods Patients – EARLY ARTHRITIS COHORTS 3115 patients from 9 cohorts Inflammatory arthritis (no other definite diagnosis) of <3 years No previous DMARD/MTX treatment Methods – PREDICTORS OF MTX TREATMENT Step 1: Univariate regression analysis of all possible variables Step 2: Principal component analysis: identify themes Step 3: Multivariate regression analysis with all relevant themes Phase 1: Three Analytic Steps Univariate Regression Analysis Identify significant variables at baseline Gold standard: MTX treatment at one year STEP 1 STEPS 1 and 2: Predictors of MTX initiation Loadings: 0 – 0.199 0.2 – 0.399 0.4 – 0.599 0.6 – 0.799 0.8 – 1 STEP 2: Relevant Themes to Predict MTX Treatment Phase 1: Results Phase 1: Conclusion Swelling of small joint regions (PIP, MCP, wrist) has independent effect Tenderness might be also be considered as “joint involvement” Symmetrical involvement does not seem to have a significant incremental effect over unilateral involvement Abnormal acute phase response has a considerable effect Serology has a considerable effect, and shows a “dose-response” relationship of titres Phases of the Project Phase 1 Data analysis Phase 2 Consensus process Phase 3 Integration of 1 and 2 Predictors of MTX initiation Final Criteria Determinants of high probability of RA Increase feasibility Phase 2 Consensus Approach Phase 2: Methods Ranking of patient profiles by experts for their probability to develop RA Evidence based discussion on discrepancies in the ranking Specifying target population Developing positive and negative determinants for risk of RA (informed by Phase 1 data) Grouping these determinants into domains and categories Weighting of each category using decision analytic software Phase 2: Overview Expert panel Phase 2: Overview Expert panel Submit case scenarios of early undifferentiated inflammatory arthritis Phase 2: Overview Expert panel Specify target population Phase 2: Overview Expert panel Specify target population Positive factors + Negative factors - Discussion on reasons for discordance among physicians Phase 2: Overview Specify target population Positive factors + Negative factors - Discussion on reasons for discordance among physicians Phase 2: Results Phases of the Project Phase 1 Data analysis Phase 2 Consensus process Phase 3 Integration of 1 and 2 Predictors of MTX initiation Final Criteria Determinants of high probability of RA Increase feasibility Phase 3 Integration of Findings from Phases 1 and 2
Slide 22 - 2010 ACR/EULAR Classification Criteria for Rheumatoid Arthritis Published in the September 2010 Issues of A&R and ARD Phases of the Project Phase 1 Data analysis Phase 2 Consensus process Phase 3 Integration of 1 and 2 Predictors of MTX initiation Final Criteria Determinants of high probability of RA Increase feasibility Phase 1 Data Driven Approach Phase 1: Patients and Methods Patients – EARLY ARTHRITIS COHORTS 3115 patients from 9 cohorts Inflammatory arthritis (no other definite diagnosis) of <3 years No previous DMARD/MTX treatment Methods – PREDICTORS OF MTX TREATMENT Step 1: Univariate regression analysis of all possible variables Step 2: Principal component analysis: identify themes Step 3: Multivariate regression analysis with all relevant themes Phase 1: Three Analytic Steps Univariate Regression Analysis Identify significant variables at baseline Gold standard: MTX treatment at one year STEP 1 STEPS 1 and 2: Predictors of MTX initiation Loadings: 0 – 0.199 0.2 – 0.399 0.4 – 0.599 0.6 – 0.799 0.8 – 1 STEP 2: Relevant Themes to Predict MTX Treatment Phase 1: Results Phase 1: Conclusion Swelling of small joint regions (PIP, MCP, wrist) has independent effect Tenderness might be also be considered as “joint involvement” Symmetrical involvement does not seem to have a significant incremental effect over unilateral involvement Abnormal acute phase response has a considerable effect Serology has a considerable effect, and shows a “dose-response” relationship of titres Phases of the Project Phase 1 Data analysis Phase 2 Consensus process Phase 3 Integration of 1 and 2 Predictors of MTX initiation Final Criteria Determinants of high probability of RA Increase feasibility Phase 2 Consensus Approach Phase 2: Methods Ranking of patient profiles by experts for their probability to develop RA Evidence based discussion on discrepancies in the ranking Specifying target population Developing positive and negative determinants for risk of RA (informed by Phase 1 data) Grouping these determinants into domains and categories Weighting of each category using decision analytic software Phase 2: Overview Expert panel Phase 2: Overview Expert panel Submit case scenarios of early undifferentiated inflammatory arthritis Phase 2: Overview Expert panel Specify target population Phase 2: Overview Expert panel Specify target population Positive factors + Negative factors - Discussion on reasons for discordance among physicians Phase 2: Overview Specify target population Positive factors + Negative factors - Discussion on reasons for discordance among physicians Phase 2: Results Phases of the Project Phase 1 Data analysis Phase 2 Consensus process Phase 3 Integration of 1 and 2 Predictors of MTX initiation Final Criteria Determinants of high probability of RA Increase feasibility Phase 3 Integration of Findings from Phases 1 and 2 Optimizing Feasibility
Slide 23 - 2010 ACR/EULAR Classification Criteria for Rheumatoid Arthritis Published in the September 2010 Issues of A&R and ARD Phases of the Project Phase 1 Data analysis Phase 2 Consensus process Phase 3 Integration of 1 and 2 Predictors of MTX initiation Final Criteria Determinants of high probability of RA Increase feasibility Phase 1 Data Driven Approach Phase 1: Patients and Methods Patients – EARLY ARTHRITIS COHORTS 3115 patients from 9 cohorts Inflammatory arthritis (no other definite diagnosis) of <3 years No previous DMARD/MTX treatment Methods – PREDICTORS OF MTX TREATMENT Step 1: Univariate regression analysis of all possible variables Step 2: Principal component analysis: identify themes Step 3: Multivariate regression analysis with all relevant themes Phase 1: Three Analytic Steps Univariate Regression Analysis Identify significant variables at baseline Gold standard: MTX treatment at one year STEP 1 STEPS 1 and 2: Predictors of MTX initiation Loadings: 0 – 0.199 0.2 – 0.399 0.4 – 0.599 0.6 – 0.799 0.8 – 1 STEP 2: Relevant Themes to Predict MTX Treatment Phase 1: Results Phase 1: Conclusion Swelling of small joint regions (PIP, MCP, wrist) has independent effect Tenderness might be also be considered as “joint involvement” Symmetrical involvement does not seem to have a significant incremental effect over unilateral involvement Abnormal acute phase response has a considerable effect Serology has a considerable effect, and shows a “dose-response” relationship of titres Phases of the Project Phase 1 Data analysis Phase 2 Consensus process Phase 3 Integration of 1 and 2 Predictors of MTX initiation Final Criteria Determinants of high probability of RA Increase feasibility Phase 2 Consensus Approach Phase 2: Methods Ranking of patient profiles by experts for their probability to develop RA Evidence based discussion on discrepancies in the ranking Specifying target population Developing positive and negative determinants for risk of RA (informed by Phase 1 data) Grouping these determinants into domains and categories Weighting of each category using decision analytic software Phase 2: Overview Expert panel Phase 2: Overview Expert panel Submit case scenarios of early undifferentiated inflammatory arthritis Phase 2: Overview Expert panel Specify target population Phase 2: Overview Expert panel Specify target population Positive factors + Negative factors - Discussion on reasons for discordance among physicians Phase 2: Overview Specify target population Positive factors + Negative factors - Discussion on reasons for discordance among physicians Phase 2: Results Phases of the Project Phase 1 Data analysis Phase 2 Consensus process Phase 3 Integration of 1 and 2 Predictors of MTX initiation Final Criteria Determinants of high probability of RA Increase feasibility Phase 3 Integration of Findings from Phases 1 and 2 Optimizing Feasibility Optimizing Feasibility
Slide 24 - 2010 ACR/EULAR Classification Criteria for Rheumatoid Arthritis Published in the September 2010 Issues of A&R and ARD Phases of the Project Phase 1 Data analysis Phase 2 Consensus process Phase 3 Integration of 1 and 2 Predictors of MTX initiation Final Criteria Determinants of high probability of RA Increase feasibility Phase 1 Data Driven Approach Phase 1: Patients and Methods Patients – EARLY ARTHRITIS COHORTS 3115 patients from 9 cohorts Inflammatory arthritis (no other definite diagnosis) of <3 years No previous DMARD/MTX treatment Methods – PREDICTORS OF MTX TREATMENT Step 1: Univariate regression analysis of all possible variables Step 2: Principal component analysis: identify themes Step 3: Multivariate regression analysis with all relevant themes Phase 1: Three Analytic Steps Univariate Regression Analysis Identify significant variables at baseline Gold standard: MTX treatment at one year STEP 1 STEPS 1 and 2: Predictors of MTX initiation Loadings: 0 – 0.199 0.2 – 0.399 0.4 – 0.599 0.6 – 0.799 0.8 – 1 STEP 2: Relevant Themes to Predict MTX Treatment Phase 1: Results Phase 1: Conclusion Swelling of small joint regions (PIP, MCP, wrist) has independent effect Tenderness might be also be considered as “joint involvement” Symmetrical involvement does not seem to have a significant incremental effect over unilateral involvement Abnormal acute phase response has a considerable effect Serology has a considerable effect, and shows a “dose-response” relationship of titres Phases of the Project Phase 1 Data analysis Phase 2 Consensus process Phase 3 Integration of 1 and 2 Predictors of MTX initiation Final Criteria Determinants of high probability of RA Increase feasibility Phase 2 Consensus Approach Phase 2: Methods Ranking of patient profiles by experts for their probability to develop RA Evidence based discussion on discrepancies in the ranking Specifying target population Developing positive and negative determinants for risk of RA (informed by Phase 1 data) Grouping these determinants into domains and categories Weighting of each category using decision analytic software Phase 2: Overview Expert panel Phase 2: Overview Expert panel Submit case scenarios of early undifferentiated inflammatory arthritis Phase 2: Overview Expert panel Specify target population Phase 2: Overview Expert panel Specify target population Positive factors + Negative factors - Discussion on reasons for discordance among physicians Phase 2: Overview Specify target population Positive factors + Negative factors - Discussion on reasons for discordance among physicians Phase 2: Results Phases of the Project Phase 1 Data analysis Phase 2 Consensus process Phase 3 Integration of 1 and 2 Predictors of MTX initiation Final Criteria Determinants of high probability of RA Increase feasibility Phase 3 Integration of Findings from Phases 1 and 2 Optimizing Feasibility Optimizing Feasibility Optimizing Feasibility
Slide 25 - 2010 ACR/EULAR Classification Criteria for Rheumatoid Arthritis Published in the September 2010 Issues of A&R and ARD Phases of the Project Phase 1 Data analysis Phase 2 Consensus process Phase 3 Integration of 1 and 2 Predictors of MTX initiation Final Criteria Determinants of high probability of RA Increase feasibility Phase 1 Data Driven Approach Phase 1: Patients and Methods Patients – EARLY ARTHRITIS COHORTS 3115 patients from 9 cohorts Inflammatory arthritis (no other definite diagnosis) of <3 years No previous DMARD/MTX treatment Methods – PREDICTORS OF MTX TREATMENT Step 1: Univariate regression analysis of all possible variables Step 2: Principal component analysis: identify themes Step 3: Multivariate regression analysis with all relevant themes Phase 1: Three Analytic Steps Univariate Regression Analysis Identify significant variables at baseline Gold standard: MTX treatment at one year STEP 1 STEPS 1 and 2: Predictors of MTX initiation Loadings: 0 – 0.199 0.2 – 0.399 0.4 – 0.599 0.6 – 0.799 0.8 – 1 STEP 2: Relevant Themes to Predict MTX Treatment Phase 1: Results Phase 1: Conclusion Swelling of small joint regions (PIP, MCP, wrist) has independent effect Tenderness might be also be considered as “joint involvement” Symmetrical involvement does not seem to have a significant incremental effect over unilateral involvement Abnormal acute phase response has a considerable effect Serology has a considerable effect, and shows a “dose-response” relationship of titres Phases of the Project Phase 1 Data analysis Phase 2 Consensus process Phase 3 Integration of 1 and 2 Predictors of MTX initiation Final Criteria Determinants of high probability of RA Increase feasibility Phase 2 Consensus Approach Phase 2: Methods Ranking of patient profiles by experts for their probability to develop RA Evidence based discussion on discrepancies in the ranking Specifying target population Developing positive and negative determinants for risk of RA (informed by Phase 1 data) Grouping these determinants into domains and categories Weighting of each category using decision analytic software Phase 2: Overview Expert panel Phase 2: Overview Expert panel Submit case scenarios of early undifferentiated inflammatory arthritis Phase 2: Overview Expert panel Specify target population Phase 2: Overview Expert panel Specify target population Positive factors + Negative factors - Discussion on reasons for discordance among physicians Phase 2: Overview Specify target population Positive factors + Negative factors - Discussion on reasons for discordance among physicians Phase 2: Results Phases of the Project Phase 1 Data analysis Phase 2 Consensus process Phase 3 Integration of 1 and 2 Predictors of MTX initiation Final Criteria Determinants of high probability of RA Increase feasibility Phase 3 Integration of Findings from Phases 1 and 2 Optimizing Feasibility Optimizing Feasibility Optimizing Feasibility Final Criteria
Slide 26 - 2010 ACR/EULAR Classification Criteria for Rheumatoid Arthritis Published in the September 2010 Issues of A&R and ARD Phases of the Project Phase 1 Data analysis Phase 2 Consensus process Phase 3 Integration of 1 and 2 Predictors of MTX initiation Final Criteria Determinants of high probability of RA Increase feasibility Phase 1 Data Driven Approach Phase 1: Patients and Methods Patients – EARLY ARTHRITIS COHORTS 3115 patients from 9 cohorts Inflammatory arthritis (no other definite diagnosis) of <3 years No previous DMARD/MTX treatment Methods – PREDICTORS OF MTX TREATMENT Step 1: Univariate regression analysis of all possible variables Step 2: Principal component analysis: identify themes Step 3: Multivariate regression analysis with all relevant themes Phase 1: Three Analytic Steps Univariate Regression Analysis Identify significant variables at baseline Gold standard: MTX treatment at one year STEP 1 STEPS 1 and 2: Predictors of MTX initiation Loadings: 0 – 0.199 0.2 – 0.399 0.4 – 0.599 0.6 – 0.799 0.8 – 1 STEP 2: Relevant Themes to Predict MTX Treatment Phase 1: Results Phase 1: Conclusion Swelling of small joint regions (PIP, MCP, wrist) has independent effect Tenderness might be also be considered as “joint involvement” Symmetrical involvement does not seem to have a significant incremental effect over unilateral involvement Abnormal acute phase response has a considerable effect Serology has a considerable effect, and shows a “dose-response” relationship of titres Phases of the Project Phase 1 Data analysis Phase 2 Consensus process Phase 3 Integration of 1 and 2 Predictors of MTX initiation Final Criteria Determinants of high probability of RA Increase feasibility Phase 2 Consensus Approach Phase 2: Methods Ranking of patient profiles by experts for their probability to develop RA Evidence based discussion on discrepancies in the ranking Specifying target population Developing positive and negative determinants for risk of RA (informed by Phase 1 data) Grouping these determinants into domains and categories Weighting of each category using decision analytic software Phase 2: Overview Expert panel Phase 2: Overview Expert panel Submit case scenarios of early undifferentiated inflammatory arthritis Phase 2: Overview Expert panel Specify target population Phase 2: Overview Expert panel Specify target population Positive factors + Negative factors - Discussion on reasons for discordance among physicians Phase 2: Overview Specify target population Positive factors + Negative factors - Discussion on reasons for discordance among physicians Phase 2: Results Phases of the Project Phase 1 Data analysis Phase 2 Consensus process Phase 3 Integration of 1 and 2 Predictors of MTX initiation Final Criteria Determinants of high probability of RA Increase feasibility Phase 3 Integration of Findings from Phases 1 and 2 Optimizing Feasibility Optimizing Feasibility Optimizing Feasibility Final Criteria Target Population of the Criteria Two requirements: (1) Patient with at least one joint with definite clinical synovitis (swelling) (2) Synovitis is not better explained by “another disease” Differential diagnoses differ in patients with different presentations. If unclear about the relevant differentials, an expert rheumatologist should be consulted.
Slide 27 - 2010 ACR/EULAR Classification Criteria for Rheumatoid Arthritis Published in the September 2010 Issues of A&R and ARD Phases of the Project Phase 1 Data analysis Phase 2 Consensus process Phase 3 Integration of 1 and 2 Predictors of MTX initiation Final Criteria Determinants of high probability of RA Increase feasibility Phase 1 Data Driven Approach Phase 1: Patients and Methods Patients – EARLY ARTHRITIS COHORTS 3115 patients from 9 cohorts Inflammatory arthritis (no other definite diagnosis) of <3 years No previous DMARD/MTX treatment Methods – PREDICTORS OF MTX TREATMENT Step 1: Univariate regression analysis of all possible variables Step 2: Principal component analysis: identify themes Step 3: Multivariate regression analysis with all relevant themes Phase 1: Three Analytic Steps Univariate Regression Analysis Identify significant variables at baseline Gold standard: MTX treatment at one year STEP 1 STEPS 1 and 2: Predictors of MTX initiation Loadings: 0 – 0.199 0.2 – 0.399 0.4 – 0.599 0.6 – 0.799 0.8 – 1 STEP 2: Relevant Themes to Predict MTX Treatment Phase 1: Results Phase 1: Conclusion Swelling of small joint regions (PIP, MCP, wrist) has independent effect Tenderness might be also be considered as “joint involvement” Symmetrical involvement does not seem to have a significant incremental effect over unilateral involvement Abnormal acute phase response has a considerable effect Serology has a considerable effect, and shows a “dose-response” relationship of titres Phases of the Project Phase 1 Data analysis Phase 2 Consensus process Phase 3 Integration of 1 and 2 Predictors of MTX initiation Final Criteria Determinants of high probability of RA Increase feasibility Phase 2 Consensus Approach Phase 2: Methods Ranking of patient profiles by experts for their probability to develop RA Evidence based discussion on discrepancies in the ranking Specifying target population Developing positive and negative determinants for risk of RA (informed by Phase 1 data) Grouping these determinants into domains and categories Weighting of each category using decision analytic software Phase 2: Overview Expert panel Phase 2: Overview Expert panel Submit case scenarios of early undifferentiated inflammatory arthritis Phase 2: Overview Expert panel Specify target population Phase 2: Overview Expert panel Specify target population Positive factors + Negative factors - Discussion on reasons for discordance among physicians Phase 2: Overview Specify target population Positive factors + Negative factors - Discussion on reasons for discordance among physicians Phase 2: Results Phases of the Project Phase 1 Data analysis Phase 2 Consensus process Phase 3 Integration of 1 and 2 Predictors of MTX initiation Final Criteria Determinants of high probability of RA Increase feasibility Phase 3 Integration of Findings from Phases 1 and 2 Optimizing Feasibility Optimizing Feasibility Optimizing Feasibility Final Criteria Target Population of the Criteria Two requirements: (1) Patient with at least one joint with definite clinical synovitis (swelling) (2) Synovitis is not better explained by “another disease” Differential diagnoses differ in patients with different presentations. If unclear about the relevant differentials, an expert rheumatologist should be consulted. 2010 ACR/EULAR Classification Criteria for RA
Slide 28 - 2010 ACR/EULAR Classification Criteria for Rheumatoid Arthritis Published in the September 2010 Issues of A&R and ARD Phases of the Project Phase 1 Data analysis Phase 2 Consensus process Phase 3 Integration of 1 and 2 Predictors of MTX initiation Final Criteria Determinants of high probability of RA Increase feasibility Phase 1 Data Driven Approach Phase 1: Patients and Methods Patients – EARLY ARTHRITIS COHORTS 3115 patients from 9 cohorts Inflammatory arthritis (no other definite diagnosis) of <3 years No previous DMARD/MTX treatment Methods – PREDICTORS OF MTX TREATMENT Step 1: Univariate regression analysis of all possible variables Step 2: Principal component analysis: identify themes Step 3: Multivariate regression analysis with all relevant themes Phase 1: Three Analytic Steps Univariate Regression Analysis Identify significant variables at baseline Gold standard: MTX treatment at one year STEP 1 STEPS 1 and 2: Predictors of MTX initiation Loadings: 0 – 0.199 0.2 – 0.399 0.4 – 0.599 0.6 – 0.799 0.8 – 1 STEP 2: Relevant Themes to Predict MTX Treatment Phase 1: Results Phase 1: Conclusion Swelling of small joint regions (PIP, MCP, wrist) has independent effect Tenderness might be also be considered as “joint involvement” Symmetrical involvement does not seem to have a significant incremental effect over unilateral involvement Abnormal acute phase response has a considerable effect Serology has a considerable effect, and shows a “dose-response” relationship of titres Phases of the Project Phase 1 Data analysis Phase 2 Consensus process Phase 3 Integration of 1 and 2 Predictors of MTX initiation Final Criteria Determinants of high probability of RA Increase feasibility Phase 2 Consensus Approach Phase 2: Methods Ranking of patient profiles by experts for their probability to develop RA Evidence based discussion on discrepancies in the ranking Specifying target population Developing positive and negative determinants for risk of RA (informed by Phase 1 data) Grouping these determinants into domains and categories Weighting of each category using decision analytic software Phase 2: Overview Expert panel Phase 2: Overview Expert panel Submit case scenarios of early undifferentiated inflammatory arthritis Phase 2: Overview Expert panel Specify target population Phase 2: Overview Expert panel Specify target population Positive factors + Negative factors - Discussion on reasons for discordance among physicians Phase 2: Overview Specify target population Positive factors + Negative factors - Discussion on reasons for discordance among physicians Phase 2: Results Phases of the Project Phase 1 Data analysis Phase 2 Consensus process Phase 3 Integration of 1 and 2 Predictors of MTX initiation Final Criteria Determinants of high probability of RA Increase feasibility Phase 3 Integration of Findings from Phases 1 and 2 Optimizing Feasibility Optimizing Feasibility Optimizing Feasibility Final Criteria Target Population of the Criteria Two requirements: (1) Patient with at least one joint with definite clinical synovitis (swelling) (2) Synovitis is not better explained by “another disease” Differential diagnoses differ in patients with different presentations. If unclear about the relevant differentials, an expert rheumatologist should be consulted. 2010 ACR/EULAR Classification Criteria for RA 2010 ACR/EULAR Classification Criteria for RA
Slide 29 - 2010 ACR/EULAR Classification Criteria for Rheumatoid Arthritis Published in the September 2010 Issues of A&R and ARD Phases of the Project Phase 1 Data analysis Phase 2 Consensus process Phase 3 Integration of 1 and 2 Predictors of MTX initiation Final Criteria Determinants of high probability of RA Increase feasibility Phase 1 Data Driven Approach Phase 1: Patients and Methods Patients – EARLY ARTHRITIS COHORTS 3115 patients from 9 cohorts Inflammatory arthritis (no other definite diagnosis) of <3 years No previous DMARD/MTX treatment Methods – PREDICTORS OF MTX TREATMENT Step 1: Univariate regression analysis of all possible variables Step 2: Principal component analysis: identify themes Step 3: Multivariate regression analysis with all relevant themes Phase 1: Three Analytic Steps Univariate Regression Analysis Identify significant variables at baseline Gold standard: MTX treatment at one year STEP 1 STEPS 1 and 2: Predictors of MTX initiation Loadings: 0 – 0.199 0.2 – 0.399 0.4 – 0.599 0.6 – 0.799 0.8 – 1 STEP 2: Relevant Themes to Predict MTX Treatment Phase 1: Results Phase 1: Conclusion Swelling of small joint regions (PIP, MCP, wrist) has independent effect Tenderness might be also be considered as “joint involvement” Symmetrical involvement does not seem to have a significant incremental effect over unilateral involvement Abnormal acute phase response has a considerable effect Serology has a considerable effect, and shows a “dose-response” relationship of titres Phases of the Project Phase 1 Data analysis Phase 2 Consensus process Phase 3 Integration of 1 and 2 Predictors of MTX initiation Final Criteria Determinants of high probability of RA Increase feasibility Phase 2 Consensus Approach Phase 2: Methods Ranking of patient profiles by experts for their probability to develop RA Evidence based discussion on discrepancies in the ranking Specifying target population Developing positive and negative determinants for risk of RA (informed by Phase 1 data) Grouping these determinants into domains and categories Weighting of each category using decision analytic software Phase 2: Overview Expert panel Phase 2: Overview Expert panel Submit case scenarios of early undifferentiated inflammatory arthritis Phase 2: Overview Expert panel Specify target population Phase 2: Overview Expert panel Specify target population Positive factors + Negative factors - Discussion on reasons for discordance among physicians Phase 2: Overview Specify target population Positive factors + Negative factors - Discussion on reasons for discordance among physicians Phase 2: Results Phases of the Project Phase 1 Data analysis Phase 2 Consensus process Phase 3 Integration of 1 and 2 Predictors of MTX initiation Final Criteria Determinants of high probability of RA Increase feasibility Phase 3 Integration of Findings from Phases 1 and 2 Optimizing Feasibility Optimizing Feasibility Optimizing Feasibility Final Criteria Target Population of the Criteria Two requirements: (1) Patient with at least one joint with definite clinical synovitis (swelling) (2) Synovitis is not better explained by “another disease” Differential diagnoses differ in patients with different presentations. If unclear about the relevant differentials, an expert rheumatologist should be consulted. 2010 ACR/EULAR Classification Criteria for RA 2010 ACR/EULAR Classification Criteria for RA 2010 ACR/EULAR Classification Criteria for RA
Slide 30 - 2010 ACR/EULAR Classification Criteria for Rheumatoid Arthritis Published in the September 2010 Issues of A&R and ARD Phases of the Project Phase 1 Data analysis Phase 2 Consensus process Phase 3 Integration of 1 and 2 Predictors of MTX initiation Final Criteria Determinants of high probability of RA Increase feasibility Phase 1 Data Driven Approach Phase 1: Patients and Methods Patients – EARLY ARTHRITIS COHORTS 3115 patients from 9 cohorts Inflammatory arthritis (no other definite diagnosis) of <3 years No previous DMARD/MTX treatment Methods – PREDICTORS OF MTX TREATMENT Step 1: Univariate regression analysis of all possible variables Step 2: Principal component analysis: identify themes Step 3: Multivariate regression analysis with all relevant themes Phase 1: Three Analytic Steps Univariate Regression Analysis Identify significant variables at baseline Gold standard: MTX treatment at one year STEP 1 STEPS 1 and 2: Predictors of MTX initiation Loadings: 0 – 0.199 0.2 – 0.399 0.4 – 0.599 0.6 – 0.799 0.8 – 1 STEP 2: Relevant Themes to Predict MTX Treatment Phase 1: Results Phase 1: Conclusion Swelling of small joint regions (PIP, MCP, wrist) has independent effect Tenderness might be also be considered as “joint involvement” Symmetrical involvement does not seem to have a significant incremental effect over unilateral involvement Abnormal acute phase response has a considerable effect Serology has a considerable effect, and shows a “dose-response” relationship of titres Phases of the Project Phase 1 Data analysis Phase 2 Consensus process Phase 3 Integration of 1 and 2 Predictors of MTX initiation Final Criteria Determinants of high probability of RA Increase feasibility Phase 2 Consensus Approach Phase 2: Methods Ranking of patient profiles by experts for their probability to develop RA Evidence based discussion on discrepancies in the ranking Specifying target population Developing positive and negative determinants for risk of RA (informed by Phase 1 data) Grouping these determinants into domains and categories Weighting of each category using decision analytic software Phase 2: Overview Expert panel Phase 2: Overview Expert panel Submit case scenarios of early undifferentiated inflammatory arthritis Phase 2: Overview Expert panel Specify target population Phase 2: Overview Expert panel Specify target population Positive factors + Negative factors - Discussion on reasons for discordance among physicians Phase 2: Overview Specify target population Positive factors + Negative factors - Discussion on reasons for discordance among physicians Phase 2: Results Phases of the Project Phase 1 Data analysis Phase 2 Consensus process Phase 3 Integration of 1 and 2 Predictors of MTX initiation Final Criteria Determinants of high probability of RA Increase feasibility Phase 3 Integration of Findings from Phases 1 and 2 Optimizing Feasibility Optimizing Feasibility Optimizing Feasibility Final Criteria Target Population of the Criteria Two requirements: (1) Patient with at least one joint with definite clinical synovitis (swelling) (2) Synovitis is not better explained by “another disease” Differential diagnoses differ in patients with different presentations. If unclear about the relevant differentials, an expert rheumatologist should be consulted. 2010 ACR/EULAR Classification Criteria for RA 2010 ACR/EULAR Classification Criteria for RA 2010 ACR/EULAR Classification Criteria for RA 2010 ACR/EULAR Classification Criteria for RA
Slide 31 - 2010 ACR/EULAR Classification Criteria for Rheumatoid Arthritis Published in the September 2010 Issues of A&R and ARD Phases of the Project Phase 1 Data analysis Phase 2 Consensus process Phase 3 Integration of 1 and 2 Predictors of MTX initiation Final Criteria Determinants of high probability of RA Increase feasibility Phase 1 Data Driven Approach Phase 1: Patients and Methods Patients – EARLY ARTHRITIS COHORTS 3115 patients from 9 cohorts Inflammatory arthritis (no other definite diagnosis) of <3 years No previous DMARD/MTX treatment Methods – PREDICTORS OF MTX TREATMENT Step 1: Univariate regression analysis of all possible variables Step 2: Principal component analysis: identify themes Step 3: Multivariate regression analysis with all relevant themes Phase 1: Three Analytic Steps Univariate Regression Analysis Identify significant variables at baseline Gold standard: MTX treatment at one year STEP 1 STEPS 1 and 2: Predictors of MTX initiation Loadings: 0 – 0.199 0.2 – 0.399 0.4 – 0.599 0.6 – 0.799 0.8 – 1 STEP 2: Relevant Themes to Predict MTX Treatment Phase 1: Results Phase 1: Conclusion Swelling of small joint regions (PIP, MCP, wrist) has independent effect Tenderness might be also be considered as “joint involvement” Symmetrical involvement does not seem to have a significant incremental effect over unilateral involvement Abnormal acute phase response has a considerable effect Serology has a considerable effect, and shows a “dose-response” relationship of titres Phases of the Project Phase 1 Data analysis Phase 2 Consensus process Phase 3 Integration of 1 and 2 Predictors of MTX initiation Final Criteria Determinants of high probability of RA Increase feasibility Phase 2 Consensus Approach Phase 2: Methods Ranking of patient profiles by experts for their probability to develop RA Evidence based discussion on discrepancies in the ranking Specifying target population Developing positive and negative determinants for risk of RA (informed by Phase 1 data) Grouping these determinants into domains and categories Weighting of each category using decision analytic software Phase 2: Overview Expert panel Phase 2: Overview Expert panel Submit case scenarios of early undifferentiated inflammatory arthritis Phase 2: Overview Expert panel Specify target population Phase 2: Overview Expert panel Specify target population Positive factors + Negative factors - Discussion on reasons for discordance among physicians Phase 2: Overview Specify target population Positive factors + Negative factors - Discussion on reasons for discordance among physicians Phase 2: Results Phases of the Project Phase 1 Data analysis Phase 2 Consensus process Phase 3 Integration of 1 and 2 Predictors of MTX initiation Final Criteria Determinants of high probability of RA Increase feasibility Phase 3 Integration of Findings from Phases 1 and 2 Optimizing Feasibility Optimizing Feasibility Optimizing Feasibility Final Criteria Target Population of the Criteria Two requirements: (1) Patient with at least one joint with definite clinical synovitis (swelling) (2) Synovitis is not better explained by “another disease” Differential diagnoses differ in patients with different presentations. If unclear about the relevant differentials, an expert rheumatologist should be consulted. 2010 ACR/EULAR Classification Criteria for RA 2010 ACR/EULAR Classification Criteria for RA 2010 ACR/EULAR Classification Criteria for RA 2010 ACR/EULAR Classification Criteria for RA 2010 ACR/EULAR Classification Criteria for RA ≥6 = definite RA What if the score is <6? Patient might fulfill the criteria…  Prospectively over time (cumulatively)  Retrospectively if data on all four domains have been adequately recorded in the past
Slide 32 - 2010 ACR/EULAR Classification Criteria for Rheumatoid Arthritis Published in the September 2010 Issues of A&R and ARD Phases of the Project Phase 1 Data analysis Phase 2 Consensus process Phase 3 Integration of 1 and 2 Predictors of MTX initiation Final Criteria Determinants of high probability of RA Increase feasibility Phase 1 Data Driven Approach Phase 1: Patients and Methods Patients – EARLY ARTHRITIS COHORTS 3115 patients from 9 cohorts Inflammatory arthritis (no other definite diagnosis) of <3 years No previous DMARD/MTX treatment Methods – PREDICTORS OF MTX TREATMENT Step 1: Univariate regression analysis of all possible variables Step 2: Principal component analysis: identify themes Step 3: Multivariate regression analysis with all relevant themes Phase 1: Three Analytic Steps Univariate Regression Analysis Identify significant variables at baseline Gold standard: MTX treatment at one year STEP 1 STEPS 1 and 2: Predictors of MTX initiation Loadings: 0 – 0.199 0.2 – 0.399 0.4 – 0.599 0.6 – 0.799 0.8 – 1 STEP 2: Relevant Themes to Predict MTX Treatment Phase 1: Results Phase 1: Conclusion Swelling of small joint regions (PIP, MCP, wrist) has independent effect Tenderness might be also be considered as “joint involvement” Symmetrical involvement does not seem to have a significant incremental effect over unilateral involvement Abnormal acute phase response has a considerable effect Serology has a considerable effect, and shows a “dose-response” relationship of titres Phases of the Project Phase 1 Data analysis Phase 2 Consensus process Phase 3 Integration of 1 and 2 Predictors of MTX initiation Final Criteria Determinants of high probability of RA Increase feasibility Phase 2 Consensus Approach Phase 2: Methods Ranking of patient profiles by experts for their probability to develop RA Evidence based discussion on discrepancies in the ranking Specifying target population Developing positive and negative determinants for risk of RA (informed by Phase 1 data) Grouping these determinants into domains and categories Weighting of each category using decision analytic software Phase 2: Overview Expert panel Phase 2: Overview Expert panel Submit case scenarios of early undifferentiated inflammatory arthritis Phase 2: Overview Expert panel Specify target population Phase 2: Overview Expert panel Specify target population Positive factors + Negative factors - Discussion on reasons for discordance among physicians Phase 2: Overview Specify target population Positive factors + Negative factors - Discussion on reasons for discordance among physicians Phase 2: Results Phases of the Project Phase 1 Data analysis Phase 2 Consensus process Phase 3 Integration of 1 and 2 Predictors of MTX initiation Final Criteria Determinants of high probability of RA Increase feasibility Phase 3 Integration of Findings from Phases 1 and 2 Optimizing Feasibility Optimizing Feasibility Optimizing Feasibility Final Criteria Target Population of the Criteria Two requirements: (1) Patient with at least one joint with definite clinical synovitis (swelling) (2) Synovitis is not better explained by “another disease” Differential diagnoses differ in patients with different presentations. If unclear about the relevant differentials, an expert rheumatologist should be consulted. 2010 ACR/EULAR Classification Criteria for RA 2010 ACR/EULAR Classification Criteria for RA 2010 ACR/EULAR Classification Criteria for RA 2010 ACR/EULAR Classification Criteria for RA 2010 ACR/EULAR Classification Criteria for RA ≥6 = definite RA What if the score is <6? Patient might fulfill the criteria…  Prospectively over time (cumulatively)  Retrospectively if data on all four domains have been adequately recorded in the past Classification vs. Diagnosis We don’t have diagnostic criteria for RA Typically in rheumatic diseases, criteria are labeled as “classification” criteria These are helpful in defining homogeneous treatment populations for study purposes A clinical “diagnosis” has to be established by the physician (rheumatologist) It includes many more aspects than can be included in formal criteria Formal classification criteria might be a guide to establish a clinical diagnosis
Slide 33 - 2010 ACR/EULAR Classification Criteria for Rheumatoid Arthritis Published in the September 2010 Issues of A&R and ARD Phases of the Project Phase 1 Data analysis Phase 2 Consensus process Phase 3 Integration of 1 and 2 Predictors of MTX initiation Final Criteria Determinants of high probability of RA Increase feasibility Phase 1 Data Driven Approach Phase 1: Patients and Methods Patients – EARLY ARTHRITIS COHORTS 3115 patients from 9 cohorts Inflammatory arthritis (no other definite diagnosis) of <3 years No previous DMARD/MTX treatment Methods – PREDICTORS OF MTX TREATMENT Step 1: Univariate regression analysis of all possible variables Step 2: Principal component analysis: identify themes Step 3: Multivariate regression analysis with all relevant themes Phase 1: Three Analytic Steps Univariate Regression Analysis Identify significant variables at baseline Gold standard: MTX treatment at one year STEP 1 STEPS 1 and 2: Predictors of MTX initiation Loadings: 0 – 0.199 0.2 – 0.399 0.4 – 0.599 0.6 – 0.799 0.8 – 1 STEP 2: Relevant Themes to Predict MTX Treatment Phase 1: Results Phase 1: Conclusion Swelling of small joint regions (PIP, MCP, wrist) has independent effect Tenderness might be also be considered as “joint involvement” Symmetrical involvement does not seem to have a significant incremental effect over unilateral involvement Abnormal acute phase response has a considerable effect Serology has a considerable effect, and shows a “dose-response” relationship of titres Phases of the Project Phase 1 Data analysis Phase 2 Consensus process Phase 3 Integration of 1 and 2 Predictors of MTX initiation Final Criteria Determinants of high probability of RA Increase feasibility Phase 2 Consensus Approach Phase 2: Methods Ranking of patient profiles by experts for their probability to develop RA Evidence based discussion on discrepancies in the ranking Specifying target population Developing positive and negative determinants for risk of RA (informed by Phase 1 data) Grouping these determinants into domains and categories Weighting of each category using decision analytic software Phase 2: Overview Expert panel Phase 2: Overview Expert panel Submit case scenarios of early undifferentiated inflammatory arthritis Phase 2: Overview Expert panel Specify target population Phase 2: Overview Expert panel Specify target population Positive factors + Negative factors - Discussion on reasons for discordance among physicians Phase 2: Overview Specify target population Positive factors + Negative factors - Discussion on reasons for discordance among physicians Phase 2: Results Phases of the Project Phase 1 Data analysis Phase 2 Consensus process Phase 3 Integration of 1 and 2 Predictors of MTX initiation Final Criteria Determinants of high probability of RA Increase feasibility Phase 3 Integration of Findings from Phases 1 and 2 Optimizing Feasibility Optimizing Feasibility Optimizing Feasibility Final Criteria Target Population of the Criteria Two requirements: (1) Patient with at least one joint with definite clinical synovitis (swelling) (2) Synovitis is not better explained by “another disease” Differential diagnoses differ in patients with different presentations. If unclear about the relevant differentials, an expert rheumatologist should be consulted. 2010 ACR/EULAR Classification Criteria for RA 2010 ACR/EULAR Classification Criteria for RA 2010 ACR/EULAR Classification Criteria for RA 2010 ACR/EULAR Classification Criteria for RA 2010 ACR/EULAR Classification Criteria for RA ≥6 = definite RA What if the score is <6? Patient might fulfill the criteria…  Prospectively over time (cumulatively)  Retrospectively if data on all four domains have been adequately recorded in the past Classification vs. Diagnosis We don’t have diagnostic criteria for RA Typically in rheumatic diseases, criteria are labeled as “classification” criteria These are helpful in defining homogeneous treatment populations for study purposes A clinical “diagnosis” has to be established by the physician (rheumatologist) It includes many more aspects than can be included in formal criteria Formal classification criteria might be a guide to establish a clinical diagnosis Classification vs. Diagnosis
Slide 34 - 2010 ACR/EULAR Classification Criteria for Rheumatoid Arthritis Published in the September 2010 Issues of A&R and ARD Phases of the Project Phase 1 Data analysis Phase 2 Consensus process Phase 3 Integration of 1 and 2 Predictors of MTX initiation Final Criteria Determinants of high probability of RA Increase feasibility Phase 1 Data Driven Approach Phase 1: Patients and Methods Patients – EARLY ARTHRITIS COHORTS 3115 patients from 9 cohorts Inflammatory arthritis (no other definite diagnosis) of <3 years No previous DMARD/MTX treatment Methods – PREDICTORS OF MTX TREATMENT Step 1: Univariate regression analysis of all possible variables Step 2: Principal component analysis: identify themes Step 3: Multivariate regression analysis with all relevant themes Phase 1: Three Analytic Steps Univariate Regression Analysis Identify significant variables at baseline Gold standard: MTX treatment at one year STEP 1 STEPS 1 and 2: Predictors of MTX initiation Loadings: 0 – 0.199 0.2 – 0.399 0.4 – 0.599 0.6 – 0.799 0.8 – 1 STEP 2: Relevant Themes to Predict MTX Treatment Phase 1: Results Phase 1: Conclusion Swelling of small joint regions (PIP, MCP, wrist) has independent effect Tenderness might be also be considered as “joint involvement” Symmetrical involvement does not seem to have a significant incremental effect over unilateral involvement Abnormal acute phase response has a considerable effect Serology has a considerable effect, and shows a “dose-response” relationship of titres Phases of the Project Phase 1 Data analysis Phase 2 Consensus process Phase 3 Integration of 1 and 2 Predictors of MTX initiation Final Criteria Determinants of high probability of RA Increase feasibility Phase 2 Consensus Approach Phase 2: Methods Ranking of patient profiles by experts for their probability to develop RA Evidence based discussion on discrepancies in the ranking Specifying target population Developing positive and negative determinants for risk of RA (informed by Phase 1 data) Grouping these determinants into domains and categories Weighting of each category using decision analytic software Phase 2: Overview Expert panel Phase 2: Overview Expert panel Submit case scenarios of early undifferentiated inflammatory arthritis Phase 2: Overview Expert panel Specify target population Phase 2: Overview Expert panel Specify target population Positive factors + Negative factors - Discussion on reasons for discordance among physicians Phase 2: Overview Specify target population Positive factors + Negative factors - Discussion on reasons for discordance among physicians Phase 2: Results Phases of the Project Phase 1 Data analysis Phase 2 Consensus process Phase 3 Integration of 1 and 2 Predictors of MTX initiation Final Criteria Determinants of high probability of RA Increase feasibility Phase 3 Integration of Findings from Phases 1 and 2 Optimizing Feasibility Optimizing Feasibility Optimizing Feasibility Final Criteria Target Population of the Criteria Two requirements: (1) Patient with at least one joint with definite clinical synovitis (swelling) (2) Synovitis is not better explained by “another disease” Differential diagnoses differ in patients with different presentations. If unclear about the relevant differentials, an expert rheumatologist should be consulted. 2010 ACR/EULAR Classification Criteria for RA 2010 ACR/EULAR Classification Criteria for RA 2010 ACR/EULAR Classification Criteria for RA 2010 ACR/EULAR Classification Criteria for RA 2010 ACR/EULAR Classification Criteria for RA ≥6 = definite RA What if the score is <6? Patient might fulfill the criteria…  Prospectively over time (cumulatively)  Retrospectively if data on all four domains have been adequately recorded in the past Classification vs. Diagnosis We don’t have diagnostic criteria for RA Typically in rheumatic diseases, criteria are labeled as “classification” criteria These are helpful in defining homogeneous treatment populations for study purposes A clinical “diagnosis” has to be established by the physician (rheumatologist) It includes many more aspects than can be included in formal criteria Formal classification criteria might be a guide to establish a clinical diagnosis Classification vs. Diagnosis Algorithm to Classification of RA Including Radiographs Longstanding inactive disease suspected? ≥6/10 on the scoring system? Not RA RA No Radiographs already available Perform radiographic assessment Yes Erosions typical for RA present? Yes ≥1 swollen joint, which is not best explained by another disease? No No No Yes Document result of the scoring system Yes Yes No
Slide 35 - 2010 ACR/EULAR Classification Criteria for Rheumatoid Arthritis Published in the September 2010 Issues of A&R and ARD Phases of the Project Phase 1 Data analysis Phase 2 Consensus process Phase 3 Integration of 1 and 2 Predictors of MTX initiation Final Criteria Determinants of high probability of RA Increase feasibility Phase 1 Data Driven Approach Phase 1: Patients and Methods Patients – EARLY ARTHRITIS COHORTS 3115 patients from 9 cohorts Inflammatory arthritis (no other definite diagnosis) of <3 years No previous DMARD/MTX treatment Methods – PREDICTORS OF MTX TREATMENT Step 1: Univariate regression analysis of all possible variables Step 2: Principal component analysis: identify themes Step 3: Multivariate regression analysis with all relevant themes Phase 1: Three Analytic Steps Univariate Regression Analysis Identify significant variables at baseline Gold standard: MTX treatment at one year STEP 1 STEPS 1 and 2: Predictors of MTX initiation Loadings: 0 – 0.199 0.2 – 0.399 0.4 – 0.599 0.6 – 0.799 0.8 – 1 STEP 2: Relevant Themes to Predict MTX Treatment Phase 1: Results Phase 1: Conclusion Swelling of small joint regions (PIP, MCP, wrist) has independent effect Tenderness might be also be considered as “joint involvement” Symmetrical involvement does not seem to have a significant incremental effect over unilateral involvement Abnormal acute phase response has a considerable effect Serology has a considerable effect, and shows a “dose-response” relationship of titres Phases of the Project Phase 1 Data analysis Phase 2 Consensus process Phase 3 Integration of 1 and 2 Predictors of MTX initiation Final Criteria Determinants of high probability of RA Increase feasibility Phase 2 Consensus Approach Phase 2: Methods Ranking of patient profiles by experts for their probability to develop RA Evidence based discussion on discrepancies in the ranking Specifying target population Developing positive and negative determinants for risk of RA (informed by Phase 1 data) Grouping these determinants into domains and categories Weighting of each category using decision analytic software Phase 2: Overview Expert panel Phase 2: Overview Expert panel Submit case scenarios of early undifferentiated inflammatory arthritis Phase 2: Overview Expert panel Specify target population Phase 2: Overview Expert panel Specify target population Positive factors + Negative factors - Discussion on reasons for discordance among physicians Phase 2: Overview Specify target population Positive factors + Negative factors - Discussion on reasons for discordance among physicians Phase 2: Results Phases of the Project Phase 1 Data analysis Phase 2 Consensus process Phase 3 Integration of 1 and 2 Predictors of MTX initiation Final Criteria Determinants of high probability of RA Increase feasibility Phase 3 Integration of Findings from Phases 1 and 2 Optimizing Feasibility Optimizing Feasibility Optimizing Feasibility Final Criteria Target Population of the Criteria Two requirements: (1) Patient with at least one joint with definite clinical synovitis (swelling) (2) Synovitis is not better explained by “another disease” Differential diagnoses differ in patients with different presentations. If unclear about the relevant differentials, an expert rheumatologist should be consulted. 2010 ACR/EULAR Classification Criteria for RA 2010 ACR/EULAR Classification Criteria for RA 2010 ACR/EULAR Classification Criteria for RA 2010 ACR/EULAR Classification Criteria for RA 2010 ACR/EULAR Classification Criteria for RA ≥6 = definite RA What if the score is <6? Patient might fulfill the criteria…  Prospectively over time (cumulatively)  Retrospectively if data on all four domains have been adequately recorded in the past Classification vs. Diagnosis We don’t have diagnostic criteria for RA Typically in rheumatic diseases, criteria are labeled as “classification” criteria These are helpful in defining homogeneous treatment populations for study purposes A clinical “diagnosis” has to be established by the physician (rheumatologist) It includes many more aspects than can be included in formal criteria Formal classification criteria might be a guide to establish a clinical diagnosis Classification vs. Diagnosis Algorithm to Classification of RA Including Radiographs Longstanding inactive disease suspected? ≥6/10 on the scoring system? Not RA RA No Radiographs already available Perform radiographic assessment Yes Erosions typical for RA present? Yes ≥1 swollen joint, which is not best explained by another disease? No No No Yes Document result of the scoring system Yes Yes No Summary: Radiographic Assessment WHEN TO PERFORM HOW TO USE The presence of typical erosions allow classification of RA even without fulfillment of the scoring system The scoring result should nevertheless be documented in clinical studies/trials Currently, there is no exact definition of “typical erosions” There is work in progress to develop the respective definitions GENERAL PRINCIPLES Radiographs are not required in the ACR/EULAR 2010 classification criteria Radiographs should not be taken for the mere purpose of classification EXCEPTIONS Radiographs should be taken in the unclassified patient in whom longstanding inactive disease is suspected (likely failed classification falsely) If radiographs are already available in an early arthritis patient, their information can be used for classification purposes. (e.g., radiographs taken by GP before referral)
Slide 36 - 2010 ACR/EULAR Classification Criteria for Rheumatoid Arthritis Published in the September 2010 Issues of A&R and ARD Phases of the Project Phase 1 Data analysis Phase 2 Consensus process Phase 3 Integration of 1 and 2 Predictors of MTX initiation Final Criteria Determinants of high probability of RA Increase feasibility Phase 1 Data Driven Approach Phase 1: Patients and Methods Patients – EARLY ARTHRITIS COHORTS 3115 patients from 9 cohorts Inflammatory arthritis (no other definite diagnosis) of <3 years No previous DMARD/MTX treatment Methods – PREDICTORS OF MTX TREATMENT Step 1: Univariate regression analysis of all possible variables Step 2: Principal component analysis: identify themes Step 3: Multivariate regression analysis with all relevant themes Phase 1: Three Analytic Steps Univariate Regression Analysis Identify significant variables at baseline Gold standard: MTX treatment at one year STEP 1 STEPS 1 and 2: Predictors of MTX initiation Loadings: 0 – 0.199 0.2 – 0.399 0.4 – 0.599 0.6 – 0.799 0.8 – 1 STEP 2: Relevant Themes to Predict MTX Treatment Phase 1: Results Phase 1: Conclusion Swelling of small joint regions (PIP, MCP, wrist) has independent effect Tenderness might be also be considered as “joint involvement” Symmetrical involvement does not seem to have a significant incremental effect over unilateral involvement Abnormal acute phase response has a considerable effect Serology has a considerable effect, and shows a “dose-response” relationship of titres Phases of the Project Phase 1 Data analysis Phase 2 Consensus process Phase 3 Integration of 1 and 2 Predictors of MTX initiation Final Criteria Determinants of high probability of RA Increase feasibility Phase 2 Consensus Approach Phase 2: Methods Ranking of patient profiles by experts for their probability to develop RA Evidence based discussion on discrepancies in the ranking Specifying target population Developing positive and negative determinants for risk of RA (informed by Phase 1 data) Grouping these determinants into domains and categories Weighting of each category using decision analytic software Phase 2: Overview Expert panel Phase 2: Overview Expert panel Submit case scenarios of early undifferentiated inflammatory arthritis Phase 2: Overview Expert panel Specify target population Phase 2: Overview Expert panel Specify target population Positive factors + Negative factors - Discussion on reasons for discordance among physicians Phase 2: Overview Specify target population Positive factors + Negative factors - Discussion on reasons for discordance among physicians Phase 2: Results Phases of the Project Phase 1 Data analysis Phase 2 Consensus process Phase 3 Integration of 1 and 2 Predictors of MTX initiation Final Criteria Determinants of high probability of RA Increase feasibility Phase 3 Integration of Findings from Phases 1 and 2 Optimizing Feasibility Optimizing Feasibility Optimizing Feasibility Final Criteria Target Population of the Criteria Two requirements: (1) Patient with at least one joint with definite clinical synovitis (swelling) (2) Synovitis is not better explained by “another disease” Differential diagnoses differ in patients with different presentations. If unclear about the relevant differentials, an expert rheumatologist should be consulted. 2010 ACR/EULAR Classification Criteria for RA 2010 ACR/EULAR Classification Criteria for RA 2010 ACR/EULAR Classification Criteria for RA 2010 ACR/EULAR Classification Criteria for RA 2010 ACR/EULAR Classification Criteria for RA ≥6 = definite RA What if the score is <6? Patient might fulfill the criteria…  Prospectively over time (cumulatively)  Retrospectively if data on all four domains have been adequately recorded in the past Classification vs. Diagnosis We don’t have diagnostic criteria for RA Typically in rheumatic diseases, criteria are labeled as “classification” criteria These are helpful in defining homogeneous treatment populations for study purposes A clinical “diagnosis” has to be established by the physician (rheumatologist) It includes many more aspects than can be included in formal criteria Formal classification criteria might be a guide to establish a clinical diagnosis Classification vs. Diagnosis Algorithm to Classification of RA Including Radiographs Longstanding inactive disease suspected? ≥6/10 on the scoring system? Not RA RA No Radiographs already available Perform radiographic assessment Yes Erosions typical for RA present? Yes ≥1 swollen joint, which is not best explained by another disease? No No No Yes Document result of the scoring system Yes Yes No Summary: Radiographic Assessment WHEN TO PERFORM HOW TO USE The presence of typical erosions allow classification of RA even without fulfillment of the scoring system The scoring result should nevertheless be documented in clinical studies/trials Currently, there is no exact definition of “typical erosions” There is work in progress to develop the respective definitions GENERAL PRINCIPLES Radiographs are not required in the ACR/EULAR 2010 classification criteria Radiographs should not be taken for the mere purpose of classification EXCEPTIONS Radiographs should be taken in the unclassified patient in whom longstanding inactive disease is suspected (likely failed classification falsely) If radiographs are already available in an early arthritis patient, their information can be used for classification purposes. (e.g., radiographs taken by GP before referral) Definitions
Slide 37 - 2010 ACR/EULAR Classification Criteria for Rheumatoid Arthritis Published in the September 2010 Issues of A&R and ARD Phases of the Project Phase 1 Data analysis Phase 2 Consensus process Phase 3 Integration of 1 and 2 Predictors of MTX initiation Final Criteria Determinants of high probability of RA Increase feasibility Phase 1 Data Driven Approach Phase 1: Patients and Methods Patients – EARLY ARTHRITIS COHORTS 3115 patients from 9 cohorts Inflammatory arthritis (no other definite diagnosis) of <3 years No previous DMARD/MTX treatment Methods – PREDICTORS OF MTX TREATMENT Step 1: Univariate regression analysis of all possible variables Step 2: Principal component analysis: identify themes Step 3: Multivariate regression analysis with all relevant themes Phase 1: Three Analytic Steps Univariate Regression Analysis Identify significant variables at baseline Gold standard: MTX treatment at one year STEP 1 STEPS 1 and 2: Predictors of MTX initiation Loadings: 0 – 0.199 0.2 – 0.399 0.4 – 0.599 0.6 – 0.799 0.8 – 1 STEP 2: Relevant Themes to Predict MTX Treatment Phase 1: Results Phase 1: Conclusion Swelling of small joint regions (PIP, MCP, wrist) has independent effect Tenderness might be also be considered as “joint involvement” Symmetrical involvement does not seem to have a significant incremental effect over unilateral involvement Abnormal acute phase response has a considerable effect Serology has a considerable effect, and shows a “dose-response” relationship of titres Phases of the Project Phase 1 Data analysis Phase 2 Consensus process Phase 3 Integration of 1 and 2 Predictors of MTX initiation Final Criteria Determinants of high probability of RA Increase feasibility Phase 2 Consensus Approach Phase 2: Methods Ranking of patient profiles by experts for their probability to develop RA Evidence based discussion on discrepancies in the ranking Specifying target population Developing positive and negative determinants for risk of RA (informed by Phase 1 data) Grouping these determinants into domains and categories Weighting of each category using decision analytic software Phase 2: Overview Expert panel Phase 2: Overview Expert panel Submit case scenarios of early undifferentiated inflammatory arthritis Phase 2: Overview Expert panel Specify target population Phase 2: Overview Expert panel Specify target population Positive factors + Negative factors - Discussion on reasons for discordance among physicians Phase 2: Overview Specify target population Positive factors + Negative factors - Discussion on reasons for discordance among physicians Phase 2: Results Phases of the Project Phase 1 Data analysis Phase 2 Consensus process Phase 3 Integration of 1 and 2 Predictors of MTX initiation Final Criteria Determinants of high probability of RA Increase feasibility Phase 3 Integration of Findings from Phases 1 and 2 Optimizing Feasibility Optimizing Feasibility Optimizing Feasibility Final Criteria Target Population of the Criteria Two requirements: (1) Patient with at least one joint with definite clinical synovitis (swelling) (2) Synovitis is not better explained by “another disease” Differential diagnoses differ in patients with different presentations. If unclear about the relevant differentials, an expert rheumatologist should be consulted. 2010 ACR/EULAR Classification Criteria for RA 2010 ACR/EULAR Classification Criteria for RA 2010 ACR/EULAR Classification Criteria for RA 2010 ACR/EULAR Classification Criteria for RA 2010 ACR/EULAR Classification Criteria for RA ≥6 = definite RA What if the score is <6? Patient might fulfill the criteria…  Prospectively over time (cumulatively)  Retrospectively if data on all four domains have been adequately recorded in the past Classification vs. Diagnosis We don’t have diagnostic criteria for RA Typically in rheumatic diseases, criteria are labeled as “classification” criteria These are helpful in defining homogeneous treatment populations for study purposes A clinical “diagnosis” has to be established by the physician (rheumatologist) It includes many more aspects than can be included in formal criteria Formal classification criteria might be a guide to establish a clinical diagnosis Classification vs. Diagnosis Algorithm to Classification of RA Including Radiographs Longstanding inactive disease suspected? ≥6/10 on the scoring system? Not RA RA No Radiographs already available Perform radiographic assessment Yes Erosions typical for RA present? Yes ≥1 swollen joint, which is not best explained by another disease? No No No Yes Document result of the scoring system Yes Yes No Summary: Radiographic Assessment WHEN TO PERFORM HOW TO USE The presence of typical erosions allow classification of RA even without fulfillment of the scoring system The scoring result should nevertheless be documented in clinical studies/trials Currently, there is no exact definition of “typical erosions” There is work in progress to develop the respective definitions GENERAL PRINCIPLES Radiographs are not required in the ACR/EULAR 2010 classification criteria Radiographs should not be taken for the mere purpose of classification EXCEPTIONS Radiographs should be taken in the unclassified patient in whom longstanding inactive disease is suspected (likely failed classification falsely) If radiographs are already available in an early arthritis patient, their information can be used for classification purposes. (e.g., radiographs taken by GP before referral) Definitions Definitions ≥6 = definite RA Definition of “JOINT INVOLVEMENT” Any swollen or tender joint (excluding DIP of hand and feet, 1st MTP, 1st CMC) Additional evidence from MRI / US may be used for confirmation of the clinical findings
Slide 38 - 2010 ACR/EULAR Classification Criteria for Rheumatoid Arthritis Published in the September 2010 Issues of A&R and ARD Phases of the Project Phase 1 Data analysis Phase 2 Consensus process Phase 3 Integration of 1 and 2 Predictors of MTX initiation Final Criteria Determinants of high probability of RA Increase feasibility Phase 1 Data Driven Approach Phase 1: Patients and Methods Patients – EARLY ARTHRITIS COHORTS 3115 patients from 9 cohorts Inflammatory arthritis (no other definite diagnosis) of <3 years No previous DMARD/MTX treatment Methods – PREDICTORS OF MTX TREATMENT Step 1: Univariate regression analysis of all possible variables Step 2: Principal component analysis: identify themes Step 3: Multivariate regression analysis with all relevant themes Phase 1: Three Analytic Steps Univariate Regression Analysis Identify significant variables at baseline Gold standard: MTX treatment at one year STEP 1 STEPS 1 and 2: Predictors of MTX initiation Loadings: 0 – 0.199 0.2 – 0.399 0.4 – 0.599 0.6 – 0.799 0.8 – 1 STEP 2: Relevant Themes to Predict MTX Treatment Phase 1: Results Phase 1: Conclusion Swelling of small joint regions (PIP, MCP, wrist) has independent effect Tenderness might be also be considered as “joint involvement” Symmetrical involvement does not seem to have a significant incremental effect over unilateral involvement Abnormal acute phase response has a considerable effect Serology has a considerable effect, and shows a “dose-response” relationship of titres Phases of the Project Phase 1 Data analysis Phase 2 Consensus process Phase 3 Integration of 1 and 2 Predictors of MTX initiation Final Criteria Determinants of high probability of RA Increase feasibility Phase 2 Consensus Approach Phase 2: Methods Ranking of patient profiles by experts for their probability to develop RA Evidence based discussion on discrepancies in the ranking Specifying target population Developing positive and negative determinants for risk of RA (informed by Phase 1 data) Grouping these determinants into domains and categories Weighting of each category using decision analytic software Phase 2: Overview Expert panel Phase 2: Overview Expert panel Submit case scenarios of early undifferentiated inflammatory arthritis Phase 2: Overview Expert panel Specify target population Phase 2: Overview Expert panel Specify target population Positive factors + Negative factors - Discussion on reasons for discordance among physicians Phase 2: Overview Specify target population Positive factors + Negative factors - Discussion on reasons for discordance among physicians Phase 2: Results Phases of the Project Phase 1 Data analysis Phase 2 Consensus process Phase 3 Integration of 1 and 2 Predictors of MTX initiation Final Criteria Determinants of high probability of RA Increase feasibility Phase 3 Integration of Findings from Phases 1 and 2 Optimizing Feasibility Optimizing Feasibility Optimizing Feasibility Final Criteria Target Population of the Criteria Two requirements: (1) Patient with at least one joint with definite clinical synovitis (swelling) (2) Synovitis is not better explained by “another disease” Differential diagnoses differ in patients with different presentations. If unclear about the relevant differentials, an expert rheumatologist should be consulted. 2010 ACR/EULAR Classification Criteria for RA 2010 ACR/EULAR Classification Criteria for RA 2010 ACR/EULAR Classification Criteria for RA 2010 ACR/EULAR Classification Criteria for RA 2010 ACR/EULAR Classification Criteria for RA ≥6 = definite RA What if the score is <6? Patient might fulfill the criteria…  Prospectively over time (cumulatively)  Retrospectively if data on all four domains have been adequately recorded in the past Classification vs. Diagnosis We don’t have diagnostic criteria for RA Typically in rheumatic diseases, criteria are labeled as “classification” criteria These are helpful in defining homogeneous treatment populations for study purposes A clinical “diagnosis” has to be established by the physician (rheumatologist) It includes many more aspects than can be included in formal criteria Formal classification criteria might be a guide to establish a clinical diagnosis Classification vs. Diagnosis Algorithm to Classification of RA Including Radiographs Longstanding inactive disease suspected? ≥6/10 on the scoring system? Not RA RA No Radiographs already available Perform radiographic assessment Yes Erosions typical for RA present? Yes ≥1 swollen joint, which is not best explained by another disease? No No No Yes Document result of the scoring system Yes Yes No Summary: Radiographic Assessment WHEN TO PERFORM HOW TO USE The presence of typical erosions allow classification of RA even without fulfillment of the scoring system The scoring result should nevertheless be documented in clinical studies/trials Currently, there is no exact definition of “typical erosions” There is work in progress to develop the respective definitions GENERAL PRINCIPLES Radiographs are not required in the ACR/EULAR 2010 classification criteria Radiographs should not be taken for the mere purpose of classification EXCEPTIONS Radiographs should be taken in the unclassified patient in whom longstanding inactive disease is suspected (likely failed classification falsely) If radiographs are already available in an early arthritis patient, their information can be used for classification purposes. (e.g., radiographs taken by GP before referral) Definitions Definitions ≥6 = definite RA Definition of “JOINT INVOLVEMENT” Any swollen or tender joint (excluding DIP of hand and feet, 1st MTP, 1st CMC) Additional evidence from MRI / US may be used for confirmation of the clinical findings Definitions ≥6 = definite RA Definition of “SMALL JOINT” MCP, PIP, MTP 2-5, thumb IP, wrist NOT: DIP, 1st CMC, 1st MTP
Slide 39 - 2010 ACR/EULAR Classification Criteria for Rheumatoid Arthritis Published in the September 2010 Issues of A&R and ARD Phases of the Project Phase 1 Data analysis Phase 2 Consensus process Phase 3 Integration of 1 and 2 Predictors of MTX initiation Final Criteria Determinants of high probability of RA Increase feasibility Phase 1 Data Driven Approach Phase 1: Patients and Methods Patients – EARLY ARTHRITIS COHORTS 3115 patients from 9 cohorts Inflammatory arthritis (no other definite diagnosis) of <3 years No previous DMARD/MTX treatment Methods – PREDICTORS OF MTX TREATMENT Step 1: Univariate regression analysis of all possible variables Step 2: Principal component analysis: identify themes Step 3: Multivariate regression analysis with all relevant themes Phase 1: Three Analytic Steps Univariate Regression Analysis Identify significant variables at baseline Gold standard: MTX treatment at one year STEP 1 STEPS 1 and 2: Predictors of MTX initiation Loadings: 0 – 0.199 0.2 – 0.399 0.4 – 0.599 0.6 – 0.799 0.8 – 1 STEP 2: Relevant Themes to Predict MTX Treatment Phase 1: Results Phase 1: Conclusion Swelling of small joint regions (PIP, MCP, wrist) has independent effect Tenderness might be also be considered as “joint involvement” Symmetrical involvement does not seem to have a significant incremental effect over unilateral involvement Abnormal acute phase response has a considerable effect Serology has a considerable effect, and shows a “dose-response” relationship of titres Phases of the Project Phase 1 Data analysis Phase 2 Consensus process Phase 3 Integration of 1 and 2 Predictors of MTX initiation Final Criteria Determinants of high probability of RA Increase feasibility Phase 2 Consensus Approach Phase 2: Methods Ranking of patient profiles by experts for their probability to develop RA Evidence based discussion on discrepancies in the ranking Specifying target population Developing positive and negative determinants for risk of RA (informed by Phase 1 data) Grouping these determinants into domains and categories Weighting of each category using decision analytic software Phase 2: Overview Expert panel Phase 2: Overview Expert panel Submit case scenarios of early undifferentiated inflammatory arthritis Phase 2: Overview Expert panel Specify target population Phase 2: Overview Expert panel Specify target population Positive factors + Negative factors - Discussion on reasons for discordance among physicians Phase 2: Overview Specify target population Positive factors + Negative factors - Discussion on reasons for discordance among physicians Phase 2: Results Phases of the Project Phase 1 Data analysis Phase 2 Consensus process Phase 3 Integration of 1 and 2 Predictors of MTX initiation Final Criteria Determinants of high probability of RA Increase feasibility Phase 3 Integration of Findings from Phases 1 and 2 Optimizing Feasibility Optimizing Feasibility Optimizing Feasibility Final Criteria Target Population of the Criteria Two requirements: (1) Patient with at least one joint with definite clinical synovitis (swelling) (2) Synovitis is not better explained by “another disease” Differential diagnoses differ in patients with different presentations. If unclear about the relevant differentials, an expert rheumatologist should be consulted. 2010 ACR/EULAR Classification Criteria for RA 2010 ACR/EULAR Classification Criteria for RA 2010 ACR/EULAR Classification Criteria for RA 2010 ACR/EULAR Classification Criteria for RA 2010 ACR/EULAR Classification Criteria for RA ≥6 = definite RA What if the score is <6? Patient might fulfill the criteria…  Prospectively over time (cumulatively)  Retrospectively if data on all four domains have been adequately recorded in the past Classification vs. Diagnosis We don’t have diagnostic criteria for RA Typically in rheumatic diseases, criteria are labeled as “classification” criteria These are helpful in defining homogeneous treatment populations for study purposes A clinical “diagnosis” has to be established by the physician (rheumatologist) It includes many more aspects than can be included in formal criteria Formal classification criteria might be a guide to establish a clinical diagnosis Classification vs. Diagnosis Algorithm to Classification of RA Including Radiographs Longstanding inactive disease suspected? ≥6/10 on the scoring system? Not RA RA No Radiographs already available Perform radiographic assessment Yes Erosions typical for RA present? Yes ≥1 swollen joint, which is not best explained by another disease? No No No Yes Document result of the scoring system Yes Yes No Summary: Radiographic Assessment WHEN TO PERFORM HOW TO USE The presence of typical erosions allow classification of RA even without fulfillment of the scoring system The scoring result should nevertheless be documented in clinical studies/trials Currently, there is no exact definition of “typical erosions” There is work in progress to develop the respective definitions GENERAL PRINCIPLES Radiographs are not required in the ACR/EULAR 2010 classification criteria Radiographs should not be taken for the mere purpose of classification EXCEPTIONS Radiographs should be taken in the unclassified patient in whom longstanding inactive disease is suspected (likely failed classification falsely) If radiographs are already available in an early arthritis patient, their information can be used for classification purposes. (e.g., radiographs taken by GP before referral) Definitions Definitions ≥6 = definite RA Definition of “JOINT INVOLVEMENT” Any swollen or tender joint (excluding DIP of hand and feet, 1st MTP, 1st CMC) Additional evidence from MRI / US may be used for confirmation of the clinical findings Definitions ≥6 = definite RA Definition of “SMALL JOINT” MCP, PIP, MTP 2-5, thumb IP, wrist NOT: DIP, 1st CMC, 1st MTP Definitions ≥6 = definite RA Definition of “LARGE JOINT” Shoulder, elbow, hip, knee, ankles
Slide 40 - 2010 ACR/EULAR Classification Criteria for Rheumatoid Arthritis Published in the September 2010 Issues of A&R and ARD Phases of the Project Phase 1 Data analysis Phase 2 Consensus process Phase 3 Integration of 1 and 2 Predictors of MTX initiation Final Criteria Determinants of high probability of RA Increase feasibility Phase 1 Data Driven Approach Phase 1: Patients and Methods Patients – EARLY ARTHRITIS COHORTS 3115 patients from 9 cohorts Inflammatory arthritis (no other definite diagnosis) of <3 years No previous DMARD/MTX treatment Methods – PREDICTORS OF MTX TREATMENT Step 1: Univariate regression analysis of all possible variables Step 2: Principal component analysis: identify themes Step 3: Multivariate regression analysis with all relevant themes Phase 1: Three Analytic Steps Univariate Regression Analysis Identify significant variables at baseline Gold standard: MTX treatment at one year STEP 1 STEPS 1 and 2: Predictors of MTX initiation Loadings: 0 – 0.199 0.2 – 0.399 0.4 – 0.599 0.6 – 0.799 0.8 – 1 STEP 2: Relevant Themes to Predict MTX Treatment Phase 1: Results Phase 1: Conclusion Swelling of small joint regions (PIP, MCP, wrist) has independent effect Tenderness might be also be considered as “joint involvement” Symmetrical involvement does not seem to have a significant incremental effect over unilateral involvement Abnormal acute phase response has a considerable effect Serology has a considerable effect, and shows a “dose-response” relationship of titres Phases of the Project Phase 1 Data analysis Phase 2 Consensus process Phase 3 Integration of 1 and 2 Predictors of MTX initiation Final Criteria Determinants of high probability of RA Increase feasibility Phase 2 Consensus Approach Phase 2: Methods Ranking of patient profiles by experts for their probability to develop RA Evidence based discussion on discrepancies in the ranking Specifying target population Developing positive and negative determinants for risk of RA (informed by Phase 1 data) Grouping these determinants into domains and categories Weighting of each category using decision analytic software Phase 2: Overview Expert panel Phase 2: Overview Expert panel Submit case scenarios of early undifferentiated inflammatory arthritis Phase 2: Overview Expert panel Specify target population Phase 2: Overview Expert panel Specify target population Positive factors + Negative factors - Discussion on reasons for discordance among physicians Phase 2: Overview Specify target population Positive factors + Negative factors - Discussion on reasons for discordance among physicians Phase 2: Results Phases of the Project Phase 1 Data analysis Phase 2 Consensus process Phase 3 Integration of 1 and 2 Predictors of MTX initiation Final Criteria Determinants of high probability of RA Increase feasibility Phase 3 Integration of Findings from Phases 1 and 2 Optimizing Feasibility Optimizing Feasibility Optimizing Feasibility Final Criteria Target Population of the Criteria Two requirements: (1) Patient with at least one joint with definite clinical synovitis (swelling) (2) Synovitis is not better explained by “another disease” Differential diagnoses differ in patients with different presentations. If unclear about the relevant differentials, an expert rheumatologist should be consulted. 2010 ACR/EULAR Classification Criteria for RA 2010 ACR/EULAR Classification Criteria for RA 2010 ACR/EULAR Classification Criteria for RA 2010 ACR/EULAR Classification Criteria for RA 2010 ACR/EULAR Classification Criteria for RA ≥6 = definite RA What if the score is <6? Patient might fulfill the criteria…  Prospectively over time (cumulatively)  Retrospectively if data on all four domains have been adequately recorded in the past Classification vs. Diagnosis We don’t have diagnostic criteria for RA Typically in rheumatic diseases, criteria are labeled as “classification” criteria These are helpful in defining homogeneous treatment populations for study purposes A clinical “diagnosis” has to be established by the physician (rheumatologist) It includes many more aspects than can be included in formal criteria Formal classification criteria might be a guide to establish a clinical diagnosis Classification vs. Diagnosis Algorithm to Classification of RA Including Radiographs Longstanding inactive disease suspected? ≥6/10 on the scoring system? Not RA RA No Radiographs already available Perform radiographic assessment Yes Erosions typical for RA present? Yes ≥1 swollen joint, which is not best explained by another disease? No No No Yes Document result of the scoring system Yes Yes No Summary: Radiographic Assessment WHEN TO PERFORM HOW TO USE The presence of typical erosions allow classification of RA even without fulfillment of the scoring system The scoring result should nevertheless be documented in clinical studies/trials Currently, there is no exact definition of “typical erosions” There is work in progress to develop the respective definitions GENERAL PRINCIPLES Radiographs are not required in the ACR/EULAR 2010 classification criteria Radiographs should not be taken for the mere purpose of classification EXCEPTIONS Radiographs should be taken in the unclassified patient in whom longstanding inactive disease is suspected (likely failed classification falsely) If radiographs are already available in an early arthritis patient, their information can be used for classification purposes. (e.g., radiographs taken by GP before referral) Definitions Definitions ≥6 = definite RA Definition of “JOINT INVOLVEMENT” Any swollen or tender joint (excluding DIP of hand and feet, 1st MTP, 1st CMC) Additional evidence from MRI / US may be used for confirmation of the clinical findings Definitions ≥6 = definite RA Definition of “SMALL JOINT” MCP, PIP, MTP 2-5, thumb IP, wrist NOT: DIP, 1st CMC, 1st MTP Definitions ≥6 = definite RA Definition of “LARGE JOINT” Shoulder, elbow, hip, knee, ankles ≥6 = definite RA Definition of “>10 JOINTS” At least one small joint Additional joints include: temporomandibular, sternoclavicular, acromioclavicular, and others (reasonably expected in RA) Definitions
Slide 41 - 2010 ACR/EULAR Classification Criteria for Rheumatoid Arthritis Published in the September 2010 Issues of A&R and ARD Phases of the Project Phase 1 Data analysis Phase 2 Consensus process Phase 3 Integration of 1 and 2 Predictors of MTX initiation Final Criteria Determinants of high probability of RA Increase feasibility Phase 1 Data Driven Approach Phase 1: Patients and Methods Patients – EARLY ARTHRITIS COHORTS 3115 patients from 9 cohorts Inflammatory arthritis (no other definite diagnosis) of <3 years No previous DMARD/MTX treatment Methods – PREDICTORS OF MTX TREATMENT Step 1: Univariate regression analysis of all possible variables Step 2: Principal component analysis: identify themes Step 3: Multivariate regression analysis with all relevant themes Phase 1: Three Analytic Steps Univariate Regression Analysis Identify significant variables at baseline Gold standard: MTX treatment at one year STEP 1 STEPS 1 and 2: Predictors of MTX initiation Loadings: 0 – 0.199 0.2 – 0.399 0.4 – 0.599 0.6 – 0.799 0.8 – 1 STEP 2: Relevant Themes to Predict MTX Treatment Phase 1: Results Phase 1: Conclusion Swelling of small joint regions (PIP, MCP, wrist) has independent effect Tenderness might be also be considered as “joint involvement” Symmetrical involvement does not seem to have a significant incremental effect over unilateral involvement Abnormal acute phase response has a considerable effect Serology has a considerable effect, and shows a “dose-response” relationship of titres Phases of the Project Phase 1 Data analysis Phase 2 Consensus process Phase 3 Integration of 1 and 2 Predictors of MTX initiation Final Criteria Determinants of high probability of RA Increase feasibility Phase 2 Consensus Approach Phase 2: Methods Ranking of patient profiles by experts for their probability to develop RA Evidence based discussion on discrepancies in the ranking Specifying target population Developing positive and negative determinants for risk of RA (informed by Phase 1 data) Grouping these determinants into domains and categories Weighting of each category using decision analytic software Phase 2: Overview Expert panel Phase 2: Overview Expert panel Submit case scenarios of early undifferentiated inflammatory arthritis Phase 2: Overview Expert panel Specify target population Phase 2: Overview Expert panel Specify target population Positive factors + Negative factors - Discussion on reasons for discordance among physicians Phase 2: Overview Specify target population Positive factors + Negative factors - Discussion on reasons for discordance among physicians Phase 2: Results Phases of the Project Phase 1 Data analysis Phase 2 Consensus process Phase 3 Integration of 1 and 2 Predictors of MTX initiation Final Criteria Determinants of high probability of RA Increase feasibility Phase 3 Integration of Findings from Phases 1 and 2 Optimizing Feasibility Optimizing Feasibility Optimizing Feasibility Final Criteria Target Population of the Criteria Two requirements: (1) Patient with at least one joint with definite clinical synovitis (swelling) (2) Synovitis is not better explained by “another disease” Differential diagnoses differ in patients with different presentations. If unclear about the relevant differentials, an expert rheumatologist should be consulted. 2010 ACR/EULAR Classification Criteria for RA 2010 ACR/EULAR Classification Criteria for RA 2010 ACR/EULAR Classification Criteria for RA 2010 ACR/EULAR Classification Criteria for RA 2010 ACR/EULAR Classification Criteria for RA ≥6 = definite RA What if the score is <6? Patient might fulfill the criteria…  Prospectively over time (cumulatively)  Retrospectively if data on all four domains have been adequately recorded in the past Classification vs. Diagnosis We don’t have diagnostic criteria for RA Typically in rheumatic diseases, criteria are labeled as “classification” criteria These are helpful in defining homogeneous treatment populations for study purposes A clinical “diagnosis” has to be established by the physician (rheumatologist) It includes many more aspects than can be included in formal criteria Formal classification criteria might be a guide to establish a clinical diagnosis Classification vs. Diagnosis Algorithm to Classification of RA Including Radiographs Longstanding inactive disease suspected? ≥6/10 on the scoring system? Not RA RA No Radiographs already available Perform radiographic assessment Yes Erosions typical for RA present? Yes ≥1 swollen joint, which is not best explained by another disease? No No No Yes Document result of the scoring system Yes Yes No Summary: Radiographic Assessment WHEN TO PERFORM HOW TO USE The presence of typical erosions allow classification of RA even without fulfillment of the scoring system The scoring result should nevertheless be documented in clinical studies/trials Currently, there is no exact definition of “typical erosions” There is work in progress to develop the respective definitions GENERAL PRINCIPLES Radiographs are not required in the ACR/EULAR 2010 classification criteria Radiographs should not be taken for the mere purpose of classification EXCEPTIONS Radiographs should be taken in the unclassified patient in whom longstanding inactive disease is suspected (likely failed classification falsely) If radiographs are already available in an early arthritis patient, their information can be used for classification purposes. (e.g., radiographs taken by GP before referral) Definitions Definitions ≥6 = definite RA Definition of “JOINT INVOLVEMENT” Any swollen or tender joint (excluding DIP of hand and feet, 1st MTP, 1st CMC) Additional evidence from MRI / US may be used for confirmation of the clinical findings Definitions ≥6 = definite RA Definition of “SMALL JOINT” MCP, PIP, MTP 2-5, thumb IP, wrist NOT: DIP, 1st CMC, 1st MTP Definitions ≥6 = definite RA Definition of “LARGE JOINT” Shoulder, elbow, hip, knee, ankles ≥6 = definite RA Definition of “>10 JOINTS” At least one small joint Additional joints include: temporomandibular, sternoclavicular, acromioclavicular, and others (reasonably expected in RA) Definitions Definitions ≥6 = definite RA Definition of “SEROLOGY” Negative: ≤ULN (for the respective lab) Low positive: >ULN but ≤3xULN High positive: >3xULN
Slide 42 - 2010 ACR/EULAR Classification Criteria for Rheumatoid Arthritis Published in the September 2010 Issues of A&R and ARD Phases of the Project Phase 1 Data analysis Phase 2 Consensus process Phase 3 Integration of 1 and 2 Predictors of MTX initiation Final Criteria Determinants of high probability of RA Increase feasibility Phase 1 Data Driven Approach Phase 1: Patients and Methods Patients – EARLY ARTHRITIS COHORTS 3115 patients from 9 cohorts Inflammatory arthritis (no other definite diagnosis) of <3 years No previous DMARD/MTX treatment Methods – PREDICTORS OF MTX TREATMENT Step 1: Univariate regression analysis of all possible variables Step 2: Principal component analysis: identify themes Step 3: Multivariate regression analysis with all relevant themes Phase 1: Three Analytic Steps Univariate Regression Analysis Identify significant variables at baseline Gold standard: MTX treatment at one year STEP 1 STEPS 1 and 2: Predictors of MTX initiation Loadings: 0 – 0.199 0.2 – 0.399 0.4 – 0.599 0.6 – 0.799 0.8 – 1 STEP 2: Relevant Themes to Predict MTX Treatment Phase 1: Results Phase 1: Conclusion Swelling of small joint regions (PIP, MCP, wrist) has independent effect Tenderness might be also be considered as “joint involvement” Symmetrical involvement does not seem to have a significant incremental effect over unilateral involvement Abnormal acute phase response has a considerable effect Serology has a considerable effect, and shows a “dose-response” relationship of titres Phases of the Project Phase 1 Data analysis Phase 2 Consensus process Phase 3 Integration of 1 and 2 Predictors of MTX initiation Final Criteria Determinants of high probability of RA Increase feasibility Phase 2 Consensus Approach Phase 2: Methods Ranking of patient profiles by experts for their probability to develop RA Evidence based discussion on discrepancies in the ranking Specifying target population Developing positive and negative determinants for risk of RA (informed by Phase 1 data) Grouping these determinants into domains and categories Weighting of each category using decision analytic software Phase 2: Overview Expert panel Phase 2: Overview Expert panel Submit case scenarios of early undifferentiated inflammatory arthritis Phase 2: Overview Expert panel Specify target population Phase 2: Overview Expert panel Specify target population Positive factors + Negative factors - Discussion on reasons for discordance among physicians Phase 2: Overview Specify target population Positive factors + Negative factors - Discussion on reasons for discordance among physicians Phase 2: Results Phases of the Project Phase 1 Data analysis Phase 2 Consensus process Phase 3 Integration of 1 and 2 Predictors of MTX initiation Final Criteria Determinants of high probability of RA Increase feasibility Phase 3 Integration of Findings from Phases 1 and 2 Optimizing Feasibility Optimizing Feasibility Optimizing Feasibility Final Criteria Target Population of the Criteria Two requirements: (1) Patient with at least one joint with definite clinical synovitis (swelling) (2) Synovitis is not better explained by “another disease” Differential diagnoses differ in patients with different presentations. If unclear about the relevant differentials, an expert rheumatologist should be consulted. 2010 ACR/EULAR Classification Criteria for RA 2010 ACR/EULAR Classification Criteria for RA 2010 ACR/EULAR Classification Criteria for RA 2010 ACR/EULAR Classification Criteria for RA 2010 ACR/EULAR Classification Criteria for RA ≥6 = definite RA What if the score is <6? Patient might fulfill the criteria…  Prospectively over time (cumulatively)  Retrospectively if data on all four domains have been adequately recorded in the past Classification vs. Diagnosis We don’t have diagnostic criteria for RA Typically in rheumatic diseases, criteria are labeled as “classification” criteria These are helpful in defining homogeneous treatment populations for study purposes A clinical “diagnosis” has to be established by the physician (rheumatologist) It includes many more aspects than can be included in formal criteria Formal classification criteria might be a guide to establish a clinical diagnosis Classification vs. Diagnosis Algorithm to Classification of RA Including Radiographs Longstanding inactive disease suspected? ≥6/10 on the scoring system? Not RA RA No Radiographs already available Perform radiographic assessment Yes Erosions typical for RA present? Yes ≥1 swollen joint, which is not best explained by another disease? No No No Yes Document result of the scoring system Yes Yes No Summary: Radiographic Assessment WHEN TO PERFORM HOW TO USE The presence of typical erosions allow classification of RA even without fulfillment of the scoring system The scoring result should nevertheless be documented in clinical studies/trials Currently, there is no exact definition of “typical erosions” There is work in progress to develop the respective definitions GENERAL PRINCIPLES Radiographs are not required in the ACR/EULAR 2010 classification criteria Radiographs should not be taken for the mere purpose of classification EXCEPTIONS Radiographs should be taken in the unclassified patient in whom longstanding inactive disease is suspected (likely failed classification falsely) If radiographs are already available in an early arthritis patient, their information can be used for classification purposes. (e.g., radiographs taken by GP before referral) Definitions Definitions ≥6 = definite RA Definition of “JOINT INVOLVEMENT” Any swollen or tender joint (excluding DIP of hand and feet, 1st MTP, 1st CMC) Additional evidence from MRI / US may be used for confirmation of the clinical findings Definitions ≥6 = definite RA Definition of “SMALL JOINT” MCP, PIP, MTP 2-5, thumb IP, wrist NOT: DIP, 1st CMC, 1st MTP Definitions ≥6 = definite RA Definition of “LARGE JOINT” Shoulder, elbow, hip, knee, ankles ≥6 = definite RA Definition of “>10 JOINTS” At least one small joint Additional joints include: temporomandibular, sternoclavicular, acromioclavicular, and others (reasonably expected in RA) Definitions Definitions ≥6 = definite RA Definition of “SEROLOGY” Negative: ≤ULN (for the respective lab) Low positive: >ULN but ≤3xULN High positive: >3xULN Definitions ≥6 = definite RA Definition of “SYMPTOM DURATION” Refers to the patient’s self-report on the maximum duration of signs and symptoms of any joint that is clinically involved at the time of assessment.
Slide 43 - 2010 ACR/EULAR Classification Criteria for Rheumatoid Arthritis Published in the September 2010 Issues of A&R and ARD Phases of the Project Phase 1 Data analysis Phase 2 Consensus process Phase 3 Integration of 1 and 2 Predictors of MTX initiation Final Criteria Determinants of high probability of RA Increase feasibility Phase 1 Data Driven Approach Phase 1: Patients and Methods Patients – EARLY ARTHRITIS COHORTS 3115 patients from 9 cohorts Inflammatory arthritis (no other definite diagnosis) of <3 years No previous DMARD/MTX treatment Methods – PREDICTORS OF MTX TREATMENT Step 1: Univariate regression analysis of all possible variables Step 2: Principal component analysis: identify themes Step 3: Multivariate regression analysis with all relevant themes Phase 1: Three Analytic Steps Univariate Regression Analysis Identify significant variables at baseline Gold standard: MTX treatment at one year STEP 1 STEPS 1 and 2: Predictors of MTX initiation Loadings: 0 – 0.199 0.2 – 0.399 0.4 – 0.599 0.6 – 0.799 0.8 – 1 STEP 2: Relevant Themes to Predict MTX Treatment Phase 1: Results Phase 1: Conclusion Swelling of small joint regions (PIP, MCP, wrist) has independent effect Tenderness might be also be considered as “joint involvement” Symmetrical involvement does not seem to have a significant incremental effect over unilateral involvement Abnormal acute phase response has a considerable effect Serology has a considerable effect, and shows a “dose-response” relationship of titres Phases of the Project Phase 1 Data analysis Phase 2 Consensus process Phase 3 Integration of 1 and 2 Predictors of MTX initiation Final Criteria Determinants of high probability of RA Increase feasibility Phase 2 Consensus Approach Phase 2: Methods Ranking of patient profiles by experts for their probability to develop RA Evidence based discussion on discrepancies in the ranking Specifying target population Developing positive and negative determinants for risk of RA (informed by Phase 1 data) Grouping these determinants into domains and categories Weighting of each category using decision analytic software Phase 2: Overview Expert panel Phase 2: Overview Expert panel Submit case scenarios of early undifferentiated inflammatory arthritis Phase 2: Overview Expert panel Specify target population Phase 2: Overview Expert panel Specify target population Positive factors + Negative factors - Discussion on reasons for discordance among physicians Phase 2: Overview Specify target population Positive factors + Negative factors - Discussion on reasons for discordance among physicians Phase 2: Results Phases of the Project Phase 1 Data analysis Phase 2 Consensus process Phase 3 Integration of 1 and 2 Predictors of MTX initiation Final Criteria Determinants of high probability of RA Increase feasibility Phase 3 Integration of Findings from Phases 1 and 2 Optimizing Feasibility Optimizing Feasibility Optimizing Feasibility Final Criteria Target Population of the Criteria Two requirements: (1) Patient with at least one joint with definite clinical synovitis (swelling) (2) Synovitis is not better explained by “another disease” Differential diagnoses differ in patients with different presentations. If unclear about the relevant differentials, an expert rheumatologist should be consulted. 2010 ACR/EULAR Classification Criteria for RA 2010 ACR/EULAR Classification Criteria for RA 2010 ACR/EULAR Classification Criteria for RA 2010 ACR/EULAR Classification Criteria for RA 2010 ACR/EULAR Classification Criteria for RA ≥6 = definite RA What if the score is <6? Patient might fulfill the criteria…  Prospectively over time (cumulatively)  Retrospectively if data on all four domains have been adequately recorded in the past Classification vs. Diagnosis We don’t have diagnostic criteria for RA Typically in rheumatic diseases, criteria are labeled as “classification” criteria These are helpful in defining homogeneous treatment populations for study purposes A clinical “diagnosis” has to be established by the physician (rheumatologist) It includes many more aspects than can be included in formal criteria Formal classification criteria might be a guide to establish a clinical diagnosis Classification vs. Diagnosis Algorithm to Classification of RA Including Radiographs Longstanding inactive disease suspected? ≥6/10 on the scoring system? Not RA RA No Radiographs already available Perform radiographic assessment Yes Erosions typical for RA present? Yes ≥1 swollen joint, which is not best explained by another disease? No No No Yes Document result of the scoring system Yes Yes No Summary: Radiographic Assessment WHEN TO PERFORM HOW TO USE The presence of typical erosions allow classification of RA even without fulfillment of the scoring system The scoring result should nevertheless be documented in clinical studies/trials Currently, there is no exact definition of “typical erosions” There is work in progress to develop the respective definitions GENERAL PRINCIPLES Radiographs are not required in the ACR/EULAR 2010 classification criteria Radiographs should not be taken for the mere purpose of classification EXCEPTIONS Radiographs should be taken in the unclassified patient in whom longstanding inactive disease is suspected (likely failed classification falsely) If radiographs are already available in an early arthritis patient, their information can be used for classification purposes. (e.g., radiographs taken by GP before referral) Definitions Definitions ≥6 = definite RA Definition of “JOINT INVOLVEMENT” Any swollen or tender joint (excluding DIP of hand and feet, 1st MTP, 1st CMC) Additional evidence from MRI / US may be used for confirmation of the clinical findings Definitions ≥6 = definite RA Definition of “SMALL JOINT” MCP, PIP, MTP 2-5, thumb IP, wrist NOT: DIP, 1st CMC, 1st MTP Definitions ≥6 = definite RA Definition of “LARGE JOINT” Shoulder, elbow, hip, knee, ankles ≥6 = definite RA Definition of “>10 JOINTS” At least one small joint Additional joints include: temporomandibular, sternoclavicular, acromioclavicular, and others (reasonably expected in RA) Definitions Definitions ≥6 = definite RA Definition of “SEROLOGY” Negative: ≤ULN (for the respective lab) Low positive: >ULN but ≤3xULN High positive: >3xULN Definitions ≥6 = definite RA Definition of “SYMPTOM DURATION” Refers to the patient’s self-report on the maximum duration of signs and symptoms of any joint that is clinically involved at the time of assessment. Algorithm for Classification Branch 4
Slide 44 - 2010 ACR/EULAR Classification Criteria for Rheumatoid Arthritis Published in the September 2010 Issues of A&R and ARD Phases of the Project Phase 1 Data analysis Phase 2 Consensus process Phase 3 Integration of 1 and 2 Predictors of MTX initiation Final Criteria Determinants of high probability of RA Increase feasibility Phase 1 Data Driven Approach Phase 1: Patients and Methods Patients – EARLY ARTHRITIS COHORTS 3115 patients from 9 cohorts Inflammatory arthritis (no other definite diagnosis) of <3 years No previous DMARD/MTX treatment Methods – PREDICTORS OF MTX TREATMENT Step 1: Univariate regression analysis of all possible variables Step 2: Principal component analysis: identify themes Step 3: Multivariate regression analysis with all relevant themes Phase 1: Three Analytic Steps Univariate Regression Analysis Identify significant variables at baseline Gold standard: MTX treatment at one year STEP 1 STEPS 1 and 2: Predictors of MTX initiation Loadings: 0 – 0.199 0.2 – 0.399 0.4 – 0.599 0.6 – 0.799 0.8 – 1 STEP 2: Relevant Themes to Predict MTX Treatment Phase 1: Results Phase 1: Conclusion Swelling of small joint regions (PIP, MCP, wrist) has independent effect Tenderness might be also be considered as “joint involvement” Symmetrical involvement does not seem to have a significant incremental effect over unilateral involvement Abnormal acute phase response has a considerable effect Serology has a considerable effect, and shows a “dose-response” relationship of titres Phases of the Project Phase 1 Data analysis Phase 2 Consensus process Phase 3 Integration of 1 and 2 Predictors of MTX initiation Final Criteria Determinants of high probability of RA Increase feasibility Phase 2 Consensus Approach Phase 2: Methods Ranking of patient profiles by experts for their probability to develop RA Evidence based discussion on discrepancies in the ranking Specifying target population Developing positive and negative determinants for risk of RA (informed by Phase 1 data) Grouping these determinants into domains and categories Weighting of each category using decision analytic software Phase 2: Overview Expert panel Phase 2: Overview Expert panel Submit case scenarios of early undifferentiated inflammatory arthritis Phase 2: Overview Expert panel Specify target population Phase 2: Overview Expert panel Specify target population Positive factors + Negative factors - Discussion on reasons for discordance among physicians Phase 2: Overview Specify target population Positive factors + Negative factors - Discussion on reasons for discordance among physicians Phase 2: Results Phases of the Project Phase 1 Data analysis Phase 2 Consensus process Phase 3 Integration of 1 and 2 Predictors of MTX initiation Final Criteria Determinants of high probability of RA Increase feasibility Phase 3 Integration of Findings from Phases 1 and 2 Optimizing Feasibility Optimizing Feasibility Optimizing Feasibility Final Criteria Target Population of the Criteria Two requirements: (1) Patient with at least one joint with definite clinical synovitis (swelling) (2) Synovitis is not better explained by “another disease” Differential diagnoses differ in patients with different presentations. If unclear about the relevant differentials, an expert rheumatologist should be consulted. 2010 ACR/EULAR Classification Criteria for RA 2010 ACR/EULAR Classification Criteria for RA 2010 ACR/EULAR Classification Criteria for RA 2010 ACR/EULAR Classification Criteria for RA 2010 ACR/EULAR Classification Criteria for RA ≥6 = definite RA What if the score is <6? Patient might fulfill the criteria…  Prospectively over time (cumulatively)  Retrospectively if data on all four domains have been adequately recorded in the past Classification vs. Diagnosis We don’t have diagnostic criteria for RA Typically in rheumatic diseases, criteria are labeled as “classification” criteria These are helpful in defining homogeneous treatment populations for study purposes A clinical “diagnosis” has to be established by the physician (rheumatologist) It includes many more aspects than can be included in formal criteria Formal classification criteria might be a guide to establish a clinical diagnosis Classification vs. Diagnosis Algorithm to Classification of RA Including Radiographs Longstanding inactive disease suspected? ≥6/10 on the scoring system? Not RA RA No Radiographs already available Perform radiographic assessment Yes Erosions typical for RA present? Yes ≥1 swollen joint, which is not best explained by another disease? No No No Yes Document result of the scoring system Yes Yes No Summary: Radiographic Assessment WHEN TO PERFORM HOW TO USE The presence of typical erosions allow classification of RA even without fulfillment of the scoring system The scoring result should nevertheless be documented in clinical studies/trials Currently, there is no exact definition of “typical erosions” There is work in progress to develop the respective definitions GENERAL PRINCIPLES Radiographs are not required in the ACR/EULAR 2010 classification criteria Radiographs should not be taken for the mere purpose of classification EXCEPTIONS Radiographs should be taken in the unclassified patient in whom longstanding inactive disease is suspected (likely failed classification falsely) If radiographs are already available in an early arthritis patient, their information can be used for classification purposes. (e.g., radiographs taken by GP before referral) Definitions Definitions ≥6 = definite RA Definition of “JOINT INVOLVEMENT” Any swollen or tender joint (excluding DIP of hand and feet, 1st MTP, 1st CMC) Additional evidence from MRI / US may be used for confirmation of the clinical findings Definitions ≥6 = definite RA Definition of “SMALL JOINT” MCP, PIP, MTP 2-5, thumb IP, wrist NOT: DIP, 1st CMC, 1st MTP Definitions ≥6 = definite RA Definition of “LARGE JOINT” Shoulder, elbow, hip, knee, ankles ≥6 = definite RA Definition of “>10 JOINTS” At least one small joint Additional joints include: temporomandibular, sternoclavicular, acromioclavicular, and others (reasonably expected in RA) Definitions Definitions ≥6 = definite RA Definition of “SEROLOGY” Negative: ≤ULN (for the respective lab) Low positive: >ULN but ≤3xULN High positive: >3xULN Definitions ≥6 = definite RA Definition of “SYMPTOM DURATION” Refers to the patient’s self-report on the maximum duration of signs and symptoms of any joint that is clinically involved at the time of assessment. Algorithm for Classification Branch 4 Branch #1: Polyarticular Presentation
Slide 45 - 2010 ACR/EULAR Classification Criteria for Rheumatoid Arthritis Published in the September 2010 Issues of A&R and ARD Phases of the Project Phase 1 Data analysis Phase 2 Consensus process Phase 3 Integration of 1 and 2 Predictors of MTX initiation Final Criteria Determinants of high probability of RA Increase feasibility Phase 1 Data Driven Approach Phase 1: Patients and Methods Patients – EARLY ARTHRITIS COHORTS 3115 patients from 9 cohorts Inflammatory arthritis (no other definite diagnosis) of <3 years No previous DMARD/MTX treatment Methods – PREDICTORS OF MTX TREATMENT Step 1: Univariate regression analysis of all possible variables Step 2: Principal component analysis: identify themes Step 3: Multivariate regression analysis with all relevant themes Phase 1: Three Analytic Steps Univariate Regression Analysis Identify significant variables at baseline Gold standard: MTX treatment at one year STEP 1 STEPS 1 and 2: Predictors of MTX initiation Loadings: 0 – 0.199 0.2 – 0.399 0.4 – 0.599 0.6 – 0.799 0.8 – 1 STEP 2: Relevant Themes to Predict MTX Treatment Phase 1: Results Phase 1: Conclusion Swelling of small joint regions (PIP, MCP, wrist) has independent effect Tenderness might be also be considered as “joint involvement” Symmetrical involvement does not seem to have a significant incremental effect over unilateral involvement Abnormal acute phase response has a considerable effect Serology has a considerable effect, and shows a “dose-response” relationship of titres Phases of the Project Phase 1 Data analysis Phase 2 Consensus process Phase 3 Integration of 1 and 2 Predictors of MTX initiation Final Criteria Determinants of high probability of RA Increase feasibility Phase 2 Consensus Approach Phase 2: Methods Ranking of patient profiles by experts for their probability to develop RA Evidence based discussion on discrepancies in the ranking Specifying target population Developing positive and negative determinants for risk of RA (informed by Phase 1 data) Grouping these determinants into domains and categories Weighting of each category using decision analytic software Phase 2: Overview Expert panel Phase 2: Overview Expert panel Submit case scenarios of early undifferentiated inflammatory arthritis Phase 2: Overview Expert panel Specify target population Phase 2: Overview Expert panel Specify target population Positive factors + Negative factors - Discussion on reasons for discordance among physicians Phase 2: Overview Specify target population Positive factors + Negative factors - Discussion on reasons for discordance among physicians Phase 2: Results Phases of the Project Phase 1 Data analysis Phase 2 Consensus process Phase 3 Integration of 1 and 2 Predictors of MTX initiation Final Criteria Determinants of high probability of RA Increase feasibility Phase 3 Integration of Findings from Phases 1 and 2 Optimizing Feasibility Optimizing Feasibility Optimizing Feasibility Final Criteria Target Population of the Criteria Two requirements: (1) Patient with at least one joint with definite clinical synovitis (swelling) (2) Synovitis is not better explained by “another disease” Differential diagnoses differ in patients with different presentations. If unclear about the relevant differentials, an expert rheumatologist should be consulted. 2010 ACR/EULAR Classification Criteria for RA 2010 ACR/EULAR Classification Criteria for RA 2010 ACR/EULAR Classification Criteria for RA 2010 ACR/EULAR Classification Criteria for RA 2010 ACR/EULAR Classification Criteria for RA ≥6 = definite RA What if the score is <6? Patient might fulfill the criteria…  Prospectively over time (cumulatively)  Retrospectively if data on all four domains have been adequately recorded in the past Classification vs. Diagnosis We don’t have diagnostic criteria for RA Typically in rheumatic diseases, criteria are labeled as “classification” criteria These are helpful in defining homogeneous treatment populations for study purposes A clinical “diagnosis” has to be established by the physician (rheumatologist) It includes many more aspects than can be included in formal criteria Formal classification criteria might be a guide to establish a clinical diagnosis Classification vs. Diagnosis Algorithm to Classification of RA Including Radiographs Longstanding inactive disease suspected? ≥6/10 on the scoring system? Not RA RA No Radiographs already available Perform radiographic assessment Yes Erosions typical for RA present? Yes ≥1 swollen joint, which is not best explained by another disease? No No No Yes Document result of the scoring system Yes Yes No Summary: Radiographic Assessment WHEN TO PERFORM HOW TO USE The presence of typical erosions allow classification of RA even without fulfillment of the scoring system The scoring result should nevertheless be documented in clinical studies/trials Currently, there is no exact definition of “typical erosions” There is work in progress to develop the respective definitions GENERAL PRINCIPLES Radiographs are not required in the ACR/EULAR 2010 classification criteria Radiographs should not be taken for the mere purpose of classification EXCEPTIONS Radiographs should be taken in the unclassified patient in whom longstanding inactive disease is suspected (likely failed classification falsely) If radiographs are already available in an early arthritis patient, their information can be used for classification purposes. (e.g., radiographs taken by GP before referral) Definitions Definitions ≥6 = definite RA Definition of “JOINT INVOLVEMENT” Any swollen or tender joint (excluding DIP of hand and feet, 1st MTP, 1st CMC) Additional evidence from MRI / US may be used for confirmation of the clinical findings Definitions ≥6 = definite RA Definition of “SMALL JOINT” MCP, PIP, MTP 2-5, thumb IP, wrist NOT: DIP, 1st CMC, 1st MTP Definitions ≥6 = definite RA Definition of “LARGE JOINT” Shoulder, elbow, hip, knee, ankles ≥6 = definite RA Definition of “>10 JOINTS” At least one small joint Additional joints include: temporomandibular, sternoclavicular, acromioclavicular, and others (reasonably expected in RA) Definitions Definitions ≥6 = definite RA Definition of “SEROLOGY” Negative: ≤ULN (for the respective lab) Low positive: >ULN but ≤3xULN High positive: >3xULN Definitions ≥6 = definite RA Definition of “SYMPTOM DURATION” Refers to the patient’s self-report on the maximum duration of signs and symptoms of any joint that is clinically involved at the time of assessment. Algorithm for Classification Branch 4 Branch #1: Polyarticular Presentation Branch #2: Presentation with Oligo/Polyarticular Small Joints RA
Slide 46 - 2010 ACR/EULAR Classification Criteria for Rheumatoid Arthritis Published in the September 2010 Issues of A&R and ARD Phases of the Project Phase 1 Data analysis Phase 2 Consensus process Phase 3 Integration of 1 and 2 Predictors of MTX initiation Final Criteria Determinants of high probability of RA Increase feasibility Phase 1 Data Driven Approach Phase 1: Patients and Methods Patients – EARLY ARTHRITIS COHORTS 3115 patients from 9 cohorts Inflammatory arthritis (no other definite diagnosis) of <3 years No previous DMARD/MTX treatment Methods – PREDICTORS OF MTX TREATMENT Step 1: Univariate regression analysis of all possible variables Step 2: Principal component analysis: identify themes Step 3: Multivariate regression analysis with all relevant themes Phase 1: Three Analytic Steps Univariate Regression Analysis Identify significant variables at baseline Gold standard: MTX treatment at one year STEP 1 STEPS 1 and 2: Predictors of MTX initiation Loadings: 0 – 0.199 0.2 – 0.399 0.4 – 0.599 0.6 – 0.799 0.8 – 1 STEP 2: Relevant Themes to Predict MTX Treatment Phase 1: Results Phase 1: Conclusion Swelling of small joint regions (PIP, MCP, wrist) has independent effect Tenderness might be also be considered as “joint involvement” Symmetrical involvement does not seem to have a significant incremental effect over unilateral involvement Abnormal acute phase response has a considerable effect Serology has a considerable effect, and shows a “dose-response” relationship of titres Phases of the Project Phase 1 Data analysis Phase 2 Consensus process Phase 3 Integration of 1 and 2 Predictors of MTX initiation Final Criteria Determinants of high probability of RA Increase feasibility Phase 2 Consensus Approach Phase 2: Methods Ranking of patient profiles by experts for their probability to develop RA Evidence based discussion on discrepancies in the ranking Specifying target population Developing positive and negative determinants for risk of RA (informed by Phase 1 data) Grouping these determinants into domains and categories Weighting of each category using decision analytic software Phase 2: Overview Expert panel Phase 2: Overview Expert panel Submit case scenarios of early undifferentiated inflammatory arthritis Phase 2: Overview Expert panel Specify target population Phase 2: Overview Expert panel Specify target population Positive factors + Negative factors - Discussion on reasons for discordance among physicians Phase 2: Overview Specify target population Positive factors + Negative factors - Discussion on reasons for discordance among physicians Phase 2: Results Phases of the Project Phase 1 Data analysis Phase 2 Consensus process Phase 3 Integration of 1 and 2 Predictors of MTX initiation Final Criteria Determinants of high probability of RA Increase feasibility Phase 3 Integration of Findings from Phases 1 and 2 Optimizing Feasibility Optimizing Feasibility Optimizing Feasibility Final Criteria Target Population of the Criteria Two requirements: (1) Patient with at least one joint with definite clinical synovitis (swelling) (2) Synovitis is not better explained by “another disease” Differential diagnoses differ in patients with different presentations. If unclear about the relevant differentials, an expert rheumatologist should be consulted. 2010 ACR/EULAR Classification Criteria for RA 2010 ACR/EULAR Classification Criteria for RA 2010 ACR/EULAR Classification Criteria for RA 2010 ACR/EULAR Classification Criteria for RA 2010 ACR/EULAR Classification Criteria for RA ≥6 = definite RA What if the score is <6? Patient might fulfill the criteria…  Prospectively over time (cumulatively)  Retrospectively if data on all four domains have been adequately recorded in the past Classification vs. Diagnosis We don’t have diagnostic criteria for RA Typically in rheumatic diseases, criteria are labeled as “classification” criteria These are helpful in defining homogeneous treatment populations for study purposes A clinical “diagnosis” has to be established by the physician (rheumatologist) It includes many more aspects than can be included in formal criteria Formal classification criteria might be a guide to establish a clinical diagnosis Classification vs. Diagnosis Algorithm to Classification of RA Including Radiographs Longstanding inactive disease suspected? ≥6/10 on the scoring system? Not RA RA No Radiographs already available Perform radiographic assessment Yes Erosions typical for RA present? Yes ≥1 swollen joint, which is not best explained by another disease? No No No Yes Document result of the scoring system Yes Yes No Summary: Radiographic Assessment WHEN TO PERFORM HOW TO USE The presence of typical erosions allow classification of RA even without fulfillment of the scoring system The scoring result should nevertheless be documented in clinical studies/trials Currently, there is no exact definition of “typical erosions” There is work in progress to develop the respective definitions GENERAL PRINCIPLES Radiographs are not required in the ACR/EULAR 2010 classification criteria Radiographs should not be taken for the mere purpose of classification EXCEPTIONS Radiographs should be taken in the unclassified patient in whom longstanding inactive disease is suspected (likely failed classification falsely) If radiographs are already available in an early arthritis patient, their information can be used for classification purposes. (e.g., radiographs taken by GP before referral) Definitions Definitions ≥6 = definite RA Definition of “JOINT INVOLVEMENT” Any swollen or tender joint (excluding DIP of hand and feet, 1st MTP, 1st CMC) Additional evidence from MRI / US may be used for confirmation of the clinical findings Definitions ≥6 = definite RA Definition of “SMALL JOINT” MCP, PIP, MTP 2-5, thumb IP, wrist NOT: DIP, 1st CMC, 1st MTP Definitions ≥6 = definite RA Definition of “LARGE JOINT” Shoulder, elbow, hip, knee, ankles ≥6 = definite RA Definition of “>10 JOINTS” At least one small joint Additional joints include: temporomandibular, sternoclavicular, acromioclavicular, and others (reasonably expected in RA) Definitions Definitions ≥6 = definite RA Definition of “SEROLOGY” Negative: ≤ULN (for the respective lab) Low positive: >ULN but ≤3xULN High positive: >3xULN Definitions ≥6 = definite RA Definition of “SYMPTOM DURATION” Refers to the patient’s self-report on the maximum duration of signs and symptoms of any joint that is clinically involved at the time of assessment. Algorithm for Classification Branch 4 Branch #1: Polyarticular Presentation Branch #2: Presentation with Oligo/Polyarticular Small Joints RA Branch #3: Presentation with Mono/Oligoarticular Small Joints Yes
Slide 47 - 2010 ACR/EULAR Classification Criteria for Rheumatoid Arthritis Published in the September 2010 Issues of A&R and ARD Phases of the Project Phase 1 Data analysis Phase 2 Consensus process Phase 3 Integration of 1 and 2 Predictors of MTX initiation Final Criteria Determinants of high probability of RA Increase feasibility Phase 1 Data Driven Approach Phase 1: Patients and Methods Patients – EARLY ARTHRITIS COHORTS 3115 patients from 9 cohorts Inflammatory arthritis (no other definite diagnosis) of <3 years No previous DMARD/MTX treatment Methods – PREDICTORS OF MTX TREATMENT Step 1: Univariate regression analysis of all possible variables Step 2: Principal component analysis: identify themes Step 3: Multivariate regression analysis with all relevant themes Phase 1: Three Analytic Steps Univariate Regression Analysis Identify significant variables at baseline Gold standard: MTX treatment at one year STEP 1 STEPS 1 and 2: Predictors of MTX initiation Loadings: 0 – 0.199 0.2 – 0.399 0.4 – 0.599 0.6 – 0.799 0.8 – 1 STEP 2: Relevant Themes to Predict MTX Treatment Phase 1: Results Phase 1: Conclusion Swelling of small joint regions (PIP, MCP, wrist) has independent effect Tenderness might be also be considered as “joint involvement” Symmetrical involvement does not seem to have a significant incremental effect over unilateral involvement Abnormal acute phase response has a considerable effect Serology has a considerable effect, and shows a “dose-response” relationship of titres Phases of the Project Phase 1 Data analysis Phase 2 Consensus process Phase 3 Integration of 1 and 2 Predictors of MTX initiation Final Criteria Determinants of high probability of RA Increase feasibility Phase 2 Consensus Approach Phase 2: Methods Ranking of patient profiles by experts for their probability to develop RA Evidence based discussion on discrepancies in the ranking Specifying target population Developing positive and negative determinants for risk of RA (informed by Phase 1 data) Grouping these determinants into domains and categories Weighting of each category using decision analytic software Phase 2: Overview Expert panel Phase 2: Overview Expert panel Submit case scenarios of early undifferentiated inflammatory arthritis Phase 2: Overview Expert panel Specify target population Phase 2: Overview Expert panel Specify target population Positive factors + Negative factors - Discussion on reasons for discordance among physicians Phase 2: Overview Specify target population Positive factors + Negative factors - Discussion on reasons for discordance among physicians Phase 2: Results Phases of the Project Phase 1 Data analysis Phase 2 Consensus process Phase 3 Integration of 1 and 2 Predictors of MTX initiation Final Criteria Determinants of high probability of RA Increase feasibility Phase 3 Integration of Findings from Phases 1 and 2 Optimizing Feasibility Optimizing Feasibility Optimizing Feasibility Final Criteria Target Population of the Criteria Two requirements: (1) Patient with at least one joint with definite clinical synovitis (swelling) (2) Synovitis is not better explained by “another disease” Differential diagnoses differ in patients with different presentations. If unclear about the relevant differentials, an expert rheumatologist should be consulted. 2010 ACR/EULAR Classification Criteria for RA 2010 ACR/EULAR Classification Criteria for RA 2010 ACR/EULAR Classification Criteria for RA 2010 ACR/EULAR Classification Criteria for RA 2010 ACR/EULAR Classification Criteria for RA ≥6 = definite RA What if the score is <6? Patient might fulfill the criteria…  Prospectively over time (cumulatively)  Retrospectively if data on all four domains have been adequately recorded in the past Classification vs. Diagnosis We don’t have diagnostic criteria for RA Typically in rheumatic diseases, criteria are labeled as “classification” criteria These are helpful in defining homogeneous treatment populations for study purposes A clinical “diagnosis” has to be established by the physician (rheumatologist) It includes many more aspects than can be included in formal criteria Formal classification criteria might be a guide to establish a clinical diagnosis Classification vs. Diagnosis Algorithm to Classification of RA Including Radiographs Longstanding inactive disease suspected? ≥6/10 on the scoring system? Not RA RA No Radiographs already available Perform radiographic assessment Yes Erosions typical for RA present? Yes ≥1 swollen joint, which is not best explained by another disease? No No No Yes Document result of the scoring system Yes Yes No Summary: Radiographic Assessment WHEN TO PERFORM HOW TO USE The presence of typical erosions allow classification of RA even without fulfillment of the scoring system The scoring result should nevertheless be documented in clinical studies/trials Currently, there is no exact definition of “typical erosions” There is work in progress to develop the respective definitions GENERAL PRINCIPLES Radiographs are not required in the ACR/EULAR 2010 classification criteria Radiographs should not be taken for the mere purpose of classification EXCEPTIONS Radiographs should be taken in the unclassified patient in whom longstanding inactive disease is suspected (likely failed classification falsely) If radiographs are already available in an early arthritis patient, their information can be used for classification purposes. (e.g., radiographs taken by GP before referral) Definitions Definitions ≥6 = definite RA Definition of “JOINT INVOLVEMENT” Any swollen or tender joint (excluding DIP of hand and feet, 1st MTP, 1st CMC) Additional evidence from MRI / US may be used for confirmation of the clinical findings Definitions ≥6 = definite RA Definition of “SMALL JOINT” MCP, PIP, MTP 2-5, thumb IP, wrist NOT: DIP, 1st CMC, 1st MTP Definitions ≥6 = definite RA Definition of “LARGE JOINT” Shoulder, elbow, hip, knee, ankles ≥6 = definite RA Definition of “>10 JOINTS” At least one small joint Additional joints include: temporomandibular, sternoclavicular, acromioclavicular, and others (reasonably expected in RA) Definitions Definitions ≥6 = definite RA Definition of “SEROLOGY” Negative: ≤ULN (for the respective lab) Low positive: >ULN but ≤3xULN High positive: >3xULN Definitions ≥6 = definite RA Definition of “SYMPTOM DURATION” Refers to the patient’s self-report on the maximum duration of signs and symptoms of any joint that is clinically involved at the time of assessment. Algorithm for Classification Branch 4 Branch #1: Polyarticular Presentation Branch #2: Presentation with Oligo/Polyarticular Small Joints RA Branch #3: Presentation with Mono/Oligoarticular Small Joints Yes Branch #3: Presentation with Oligo/Polyarticular Large Joints
Slide 48 - 2010 ACR/EULAR Classification Criteria for Rheumatoid Arthritis Published in the September 2010 Issues of A&R and ARD Phases of the Project Phase 1 Data analysis Phase 2 Consensus process Phase 3 Integration of 1 and 2 Predictors of MTX initiation Final Criteria Determinants of high probability of RA Increase feasibility Phase 1 Data Driven Approach Phase 1: Patients and Methods Patients – EARLY ARTHRITIS COHORTS 3115 patients from 9 cohorts Inflammatory arthritis (no other definite diagnosis) of <3 years No previous DMARD/MTX treatment Methods – PREDICTORS OF MTX TREATMENT Step 1: Univariate regression analysis of all possible variables Step 2: Principal component analysis: identify themes Step 3: Multivariate regression analysis with all relevant themes Phase 1: Three Analytic Steps Univariate Regression Analysis Identify significant variables at baseline Gold standard: MTX treatment at one year STEP 1 STEPS 1 and 2: Predictors of MTX initiation Loadings: 0 – 0.199 0.2 – 0.399 0.4 – 0.599 0.6 – 0.799 0.8 – 1 STEP 2: Relevant Themes to Predict MTX Treatment Phase 1: Results Phase 1: Conclusion Swelling of small joint regions (PIP, MCP, wrist) has independent effect Tenderness might be also be considered as “joint involvement” Symmetrical involvement does not seem to have a significant incremental effect over unilateral involvement Abnormal acute phase response has a considerable effect Serology has a considerable effect, and shows a “dose-response” relationship of titres Phases of the Project Phase 1 Data analysis Phase 2 Consensus process Phase 3 Integration of 1 and 2 Predictors of MTX initiation Final Criteria Determinants of high probability of RA Increase feasibility Phase 2 Consensus Approach Phase 2: Methods Ranking of patient profiles by experts for their probability to develop RA Evidence based discussion on discrepancies in the ranking Specifying target population Developing positive and negative determinants for risk of RA (informed by Phase 1 data) Grouping these determinants into domains and categories Weighting of each category using decision analytic software Phase 2: Overview Expert panel Phase 2: Overview Expert panel Submit case scenarios of early undifferentiated inflammatory arthritis Phase 2: Overview Expert panel Specify target population Phase 2: Overview Expert panel Specify target population Positive factors + Negative factors - Discussion on reasons for discordance among physicians Phase 2: Overview Specify target population Positive factors + Negative factors - Discussion on reasons for discordance among physicians Phase 2: Results Phases of the Project Phase 1 Data analysis Phase 2 Consensus process Phase 3 Integration of 1 and 2 Predictors of MTX initiation Final Criteria Determinants of high probability of RA Increase feasibility Phase 3 Integration of Findings from Phases 1 and 2 Optimizing Feasibility Optimizing Feasibility Optimizing Feasibility Final Criteria Target Population of the Criteria Two requirements: (1) Patient with at least one joint with definite clinical synovitis (swelling) (2) Synovitis is not better explained by “another disease” Differential diagnoses differ in patients with different presentations. If unclear about the relevant differentials, an expert rheumatologist should be consulted. 2010 ACR/EULAR Classification Criteria for RA 2010 ACR/EULAR Classification Criteria for RA 2010 ACR/EULAR Classification Criteria for RA 2010 ACR/EULAR Classification Criteria for RA 2010 ACR/EULAR Classification Criteria for RA ≥6 = definite RA What if the score is <6? Patient might fulfill the criteria…  Prospectively over time (cumulatively)  Retrospectively if data on all four domains have been adequately recorded in the past Classification vs. Diagnosis We don’t have diagnostic criteria for RA Typically in rheumatic diseases, criteria are labeled as “classification” criteria These are helpful in defining homogeneous treatment populations for study purposes A clinical “diagnosis” has to be established by the physician (rheumatologist) It includes many more aspects than can be included in formal criteria Formal classification criteria might be a guide to establish a clinical diagnosis Classification vs. Diagnosis Algorithm to Classification of RA Including Radiographs Longstanding inactive disease suspected? ≥6/10 on the scoring system? Not RA RA No Radiographs already available Perform radiographic assessment Yes Erosions typical for RA present? Yes ≥1 swollen joint, which is not best explained by another disease? No No No Yes Document result of the scoring system Yes Yes No Summary: Radiographic Assessment WHEN TO PERFORM HOW TO USE The presence of typical erosions allow classification of RA even without fulfillment of the scoring system The scoring result should nevertheless be documented in clinical studies/trials Currently, there is no exact definition of “typical erosions” There is work in progress to develop the respective definitions GENERAL PRINCIPLES Radiographs are not required in the ACR/EULAR 2010 classification criteria Radiographs should not be taken for the mere purpose of classification EXCEPTIONS Radiographs should be taken in the unclassified patient in whom longstanding inactive disease is suspected (likely failed classification falsely) If radiographs are already available in an early arthritis patient, their information can be used for classification purposes. (e.g., radiographs taken by GP before referral) Definitions Definitions ≥6 = definite RA Definition of “JOINT INVOLVEMENT” Any swollen or tender joint (excluding DIP of hand and feet, 1st MTP, 1st CMC) Additional evidence from MRI / US may be used for confirmation of the clinical findings Definitions ≥6 = definite RA Definition of “SMALL JOINT” MCP, PIP, MTP 2-5, thumb IP, wrist NOT: DIP, 1st CMC, 1st MTP Definitions ≥6 = definite RA Definition of “LARGE JOINT” Shoulder, elbow, hip, knee, ankles ≥6 = definite RA Definition of “>10 JOINTS” At least one small joint Additional joints include: temporomandibular, sternoclavicular, acromioclavicular, and others (reasonably expected in RA) Definitions Definitions ≥6 = definite RA Definition of “SEROLOGY” Negative: ≤ULN (for the respective lab) Low positive: >ULN but ≤3xULN High positive: >3xULN Definitions ≥6 = definite RA Definition of “SYMPTOM DURATION” Refers to the patient’s self-report on the maximum duration of signs and symptoms of any joint that is clinically involved at the time of assessment. Algorithm for Classification Branch 4 Branch #1: Polyarticular Presentation Branch #2: Presentation with Oligo/Polyarticular Small Joints RA Branch #3: Presentation with Mono/Oligoarticular Small Joints Yes Branch #3: Presentation with Oligo/Polyarticular Large Joints START (eligible patient) RA RA RA RA RA RA RA RA >10 joints (at least one small joint) 4-10 small joints 1-3 small joints 2-10 large (no small) joints No No No Serology: +/++ Yes Yes No No No Yes Yes Duration: ≥6 weeks Duration: ≥6 weeks Duration: ≥6 weeks Duration: ≥6 weeks Serology: ++ Serology: + Serology: ++ Serology: ++ APR: Abnormal APR: Abnormal APR: Abnormal APR: Abnormal Yes Yes Yes Yes Yes No No No No No No No Yes Yes Yes Yes No Yes No Yes No Yes No Yes Duration: ≥6 weeks Serology: + Yes No No Yes Rheumatoid arthritis No classification of rheumatoid arthritis APR: Abnormal
Slide 49 - 2010 ACR/EULAR Classification Criteria for Rheumatoid Arthritis Published in the September 2010 Issues of A&R and ARD Phases of the Project Phase 1 Data analysis Phase 2 Consensus process Phase 3 Integration of 1 and 2 Predictors of MTX initiation Final Criteria Determinants of high probability of RA Increase feasibility Phase 1 Data Driven Approach Phase 1: Patients and Methods Patients – EARLY ARTHRITIS COHORTS 3115 patients from 9 cohorts Inflammatory arthritis (no other definite diagnosis) of <3 years No previous DMARD/MTX treatment Methods – PREDICTORS OF MTX TREATMENT Step 1: Univariate regression analysis of all possible variables Step 2: Principal component analysis: identify themes Step 3: Multivariate regression analysis with all relevant themes Phase 1: Three Analytic Steps Univariate Regression Analysis Identify significant variables at baseline Gold standard: MTX treatment at one year STEP 1 STEPS 1 and 2: Predictors of MTX initiation Loadings: 0 – 0.199 0.2 – 0.399 0.4 – 0.599 0.6 – 0.799 0.8 – 1 STEP 2: Relevant Themes to Predict MTX Treatment Phase 1: Results Phase 1: Conclusion Swelling of small joint regions (PIP, MCP, wrist) has independent effect Tenderness might be also be considered as “joint involvement” Symmetrical involvement does not seem to have a significant incremental effect over unilateral involvement Abnormal acute phase response has a considerable effect Serology has a considerable effect, and shows a “dose-response” relationship of titres Phases of the Project Phase 1 Data analysis Phase 2 Consensus process Phase 3 Integration of 1 and 2 Predictors of MTX initiation Final Criteria Determinants of high probability of RA Increase feasibility Phase 2 Consensus Approach Phase 2: Methods Ranking of patient profiles by experts for their probability to develop RA Evidence based discussion on discrepancies in the ranking Specifying target population Developing positive and negative determinants for risk of RA (informed by Phase 1 data) Grouping these determinants into domains and categories Weighting of each category using decision analytic software Phase 2: Overview Expert panel Phase 2: Overview Expert panel Submit case scenarios of early undifferentiated inflammatory arthritis Phase 2: Overview Expert panel Specify target population Phase 2: Overview Expert panel Specify target population Positive factors + Negative factors - Discussion on reasons for discordance among physicians Phase 2: Overview Specify target population Positive factors + Negative factors - Discussion on reasons for discordance among physicians Phase 2: Results Phases of the Project Phase 1 Data analysis Phase 2 Consensus process Phase 3 Integration of 1 and 2 Predictors of MTX initiation Final Criteria Determinants of high probability of RA Increase feasibility Phase 3 Integration of Findings from Phases 1 and 2 Optimizing Feasibility Optimizing Feasibility Optimizing Feasibility Final Criteria Target Population of the Criteria Two requirements: (1) Patient with at least one joint with definite clinical synovitis (swelling) (2) Synovitis is not better explained by “another disease” Differential diagnoses differ in patients with different presentations. If unclear about the relevant differentials, an expert rheumatologist should be consulted. 2010 ACR/EULAR Classification Criteria for RA 2010 ACR/EULAR Classification Criteria for RA 2010 ACR/EULAR Classification Criteria for RA 2010 ACR/EULAR Classification Criteria for RA 2010 ACR/EULAR Classification Criteria for RA ≥6 = definite RA What if the score is <6? Patient might fulfill the criteria…  Prospectively over time (cumulatively)  Retrospectively if data on all four domains have been adequately recorded in the past Classification vs. Diagnosis We don’t have diagnostic criteria for RA Typically in rheumatic diseases, criteria are labeled as “classification” criteria These are helpful in defining homogeneous treatment populations for study purposes A clinical “diagnosis” has to be established by the physician (rheumatologist) It includes many more aspects than can be included in formal criteria Formal classification criteria might be a guide to establish a clinical diagnosis Classification vs. Diagnosis Algorithm to Classification of RA Including Radiographs Longstanding inactive disease suspected? ≥6/10 on the scoring system? Not RA RA No Radiographs already available Perform radiographic assessment Yes Erosions typical for RA present? Yes ≥1 swollen joint, which is not best explained by another disease? No No No Yes Document result of the scoring system Yes Yes No Summary: Radiographic Assessment WHEN TO PERFORM HOW TO USE The presence of typical erosions allow classification of RA even without fulfillment of the scoring system The scoring result should nevertheless be documented in clinical studies/trials Currently, there is no exact definition of “typical erosions” There is work in progress to develop the respective definitions GENERAL PRINCIPLES Radiographs are not required in the ACR/EULAR 2010 classification criteria Radiographs should not be taken for the mere purpose of classification EXCEPTIONS Radiographs should be taken in the unclassified patient in whom longstanding inactive disease is suspected (likely failed classification falsely) If radiographs are already available in an early arthritis patient, their information can be used for classification purposes. (e.g., radiographs taken by GP before referral) Definitions Definitions ≥6 = definite RA Definition of “JOINT INVOLVEMENT” Any swollen or tender joint (excluding DIP of hand and feet, 1st MTP, 1st CMC) Additional evidence from MRI / US may be used for confirmation of the clinical findings Definitions ≥6 = definite RA Definition of “SMALL JOINT” MCP, PIP, MTP 2-5, thumb IP, wrist NOT: DIP, 1st CMC, 1st MTP Definitions ≥6 = definite RA Definition of “LARGE JOINT” Shoulder, elbow, hip, knee, ankles ≥6 = definite RA Definition of “>10 JOINTS” At least one small joint Additional joints include: temporomandibular, sternoclavicular, acromioclavicular, and others (reasonably expected in RA) Definitions Definitions ≥6 = definite RA Definition of “SEROLOGY” Negative: ≤ULN (for the respective lab) Low positive: >ULN but ≤3xULN High positive: >3xULN Definitions ≥6 = definite RA Definition of “SYMPTOM DURATION” Refers to the patient’s self-report on the maximum duration of signs and symptoms of any joint that is clinically involved at the time of assessment. Algorithm for Classification Branch 4 Branch #1: Polyarticular Presentation Branch #2: Presentation with Oligo/Polyarticular Small Joints RA Branch #3: Presentation with Mono/Oligoarticular Small Joints Yes Branch #3: Presentation with Oligo/Polyarticular Large Joints START (eligible patient) RA RA RA RA RA RA RA RA >10 joints (at least one small joint) 4-10 small joints 1-3 small joints 2-10 large (no small) joints No No No Serology: +/++ Yes Yes No No No Yes Yes Duration: ≥6 weeks Duration: ≥6 weeks Duration: ≥6 weeks Duration: ≥6 weeks Serology: ++ Serology: + Serology: ++ Serology: ++ APR: Abnormal APR: Abnormal APR: Abnormal APR: Abnormal Yes Yes Yes Yes Yes No No No No No No No Yes Yes Yes Yes No Yes No Yes No Yes No Yes Duration: ≥6 weeks Serology: + Yes No No Yes Rheumatoid arthritis No classification of rheumatoid arthritis APR: Abnormal Example: False Positive Classification ≥6 = definite RA CASE SCENARIO Inflammatory Osteoarthritis One clinically inflamed OA joint (PIP 3 right hand) Tenderness of all DIPs, PIPs, thumb IPs, CMC 1, and knees Seronegative Long standing disease Normal acute phase If OA is clinically apparent, then this patient would not be in the target population of the criteria
Slide 50 - 2010 ACR/EULAR Classification Criteria for Rheumatoid Arthritis Published in the September 2010 Issues of A&R and ARD Phases of the Project Phase 1 Data analysis Phase 2 Consensus process Phase 3 Integration of 1 and 2 Predictors of MTX initiation Final Criteria Determinants of high probability of RA Increase feasibility Phase 1 Data Driven Approach Phase 1: Patients and Methods Patients – EARLY ARTHRITIS COHORTS 3115 patients from 9 cohorts Inflammatory arthritis (no other definite diagnosis) of <3 years No previous DMARD/MTX treatment Methods – PREDICTORS OF MTX TREATMENT Step 1: Univariate regression analysis of all possible variables Step 2: Principal component analysis: identify themes Step 3: Multivariate regression analysis with all relevant themes Phase 1: Three Analytic Steps Univariate Regression Analysis Identify significant variables at baseline Gold standard: MTX treatment at one year STEP 1 STEPS 1 and 2: Predictors of MTX initiation Loadings: 0 – 0.199 0.2 – 0.399 0.4 – 0.599 0.6 – 0.799 0.8 – 1 STEP 2: Relevant Themes to Predict MTX Treatment Phase 1: Results Phase 1: Conclusion Swelling of small joint regions (PIP, MCP, wrist) has independent effect Tenderness might be also be considered as “joint involvement” Symmetrical involvement does not seem to have a significant incremental effect over unilateral involvement Abnormal acute phase response has a considerable effect Serology has a considerable effect, and shows a “dose-response” relationship of titres Phases of the Project Phase 1 Data analysis Phase 2 Consensus process Phase 3 Integration of 1 and 2 Predictors of MTX initiation Final Criteria Determinants of high probability of RA Increase feasibility Phase 2 Consensus Approach Phase 2: Methods Ranking of patient profiles by experts for their probability to develop RA Evidence based discussion on discrepancies in the ranking Specifying target population Developing positive and negative determinants for risk of RA (informed by Phase 1 data) Grouping these determinants into domains and categories Weighting of each category using decision analytic software Phase 2: Overview Expert panel Phase 2: Overview Expert panel Submit case scenarios of early undifferentiated inflammatory arthritis Phase 2: Overview Expert panel Specify target population Phase 2: Overview Expert panel Specify target population Positive factors + Negative factors - Discussion on reasons for discordance among physicians Phase 2: Overview Specify target population Positive factors + Negative factors - Discussion on reasons for discordance among physicians Phase 2: Results Phases of the Project Phase 1 Data analysis Phase 2 Consensus process Phase 3 Integration of 1 and 2 Predictors of MTX initiation Final Criteria Determinants of high probability of RA Increase feasibility Phase 3 Integration of Findings from Phases 1 and 2 Optimizing Feasibility Optimizing Feasibility Optimizing Feasibility Final Criteria Target Population of the Criteria Two requirements: (1) Patient with at least one joint with definite clinical synovitis (swelling) (2) Synovitis is not better explained by “another disease” Differential diagnoses differ in patients with different presentations. If unclear about the relevant differentials, an expert rheumatologist should be consulted. 2010 ACR/EULAR Classification Criteria for RA 2010 ACR/EULAR Classification Criteria for RA 2010 ACR/EULAR Classification Criteria for RA 2010 ACR/EULAR Classification Criteria for RA 2010 ACR/EULAR Classification Criteria for RA ≥6 = definite RA What if the score is <6? Patient might fulfill the criteria…  Prospectively over time (cumulatively)  Retrospectively if data on all four domains have been adequately recorded in the past Classification vs. Diagnosis We don’t have diagnostic criteria for RA Typically in rheumatic diseases, criteria are labeled as “classification” criteria These are helpful in defining homogeneous treatment populations for study purposes A clinical “diagnosis” has to be established by the physician (rheumatologist) It includes many more aspects than can be included in formal criteria Formal classification criteria might be a guide to establish a clinical diagnosis Classification vs. Diagnosis Algorithm to Classification of RA Including Radiographs Longstanding inactive disease suspected? ≥6/10 on the scoring system? Not RA RA No Radiographs already available Perform radiographic assessment Yes Erosions typical for RA present? Yes ≥1 swollen joint, which is not best explained by another disease? No No No Yes Document result of the scoring system Yes Yes No Summary: Radiographic Assessment WHEN TO PERFORM HOW TO USE The presence of typical erosions allow classification of RA even without fulfillment of the scoring system The scoring result should nevertheless be documented in clinical studies/trials Currently, there is no exact definition of “typical erosions” There is work in progress to develop the respective definitions GENERAL PRINCIPLES Radiographs are not required in the ACR/EULAR 2010 classification criteria Radiographs should not be taken for the mere purpose of classification EXCEPTIONS Radiographs should be taken in the unclassified patient in whom longstanding inactive disease is suspected (likely failed classification falsely) If radiographs are already available in an early arthritis patient, their information can be used for classification purposes. (e.g., radiographs taken by GP before referral) Definitions Definitions ≥6 = definite RA Definition of “JOINT INVOLVEMENT” Any swollen or tender joint (excluding DIP of hand and feet, 1st MTP, 1st CMC) Additional evidence from MRI / US may be used for confirmation of the clinical findings Definitions ≥6 = definite RA Definition of “SMALL JOINT” MCP, PIP, MTP 2-5, thumb IP, wrist NOT: DIP, 1st CMC, 1st MTP Definitions ≥6 = definite RA Definition of “LARGE JOINT” Shoulder, elbow, hip, knee, ankles ≥6 = definite RA Definition of “>10 JOINTS” At least one small joint Additional joints include: temporomandibular, sternoclavicular, acromioclavicular, and others (reasonably expected in RA) Definitions Definitions ≥6 = definite RA Definition of “SEROLOGY” Negative: ≤ULN (for the respective lab) Low positive: >ULN but ≤3xULN High positive: >3xULN Definitions ≥6 = definite RA Definition of “SYMPTOM DURATION” Refers to the patient’s self-report on the maximum duration of signs and symptoms of any joint that is clinically involved at the time of assessment. Algorithm for Classification Branch 4 Branch #1: Polyarticular Presentation Branch #2: Presentation with Oligo/Polyarticular Small Joints RA Branch #3: Presentation with Mono/Oligoarticular Small Joints Yes Branch #3: Presentation with Oligo/Polyarticular Large Joints START (eligible patient) RA RA RA RA RA RA RA RA >10 joints (at least one small joint) 4-10 small joints 1-3 small joints 2-10 large (no small) joints No No No Serology: +/++ Yes Yes No No No Yes Yes Duration: ≥6 weeks Duration: ≥6 weeks Duration: ≥6 weeks Duration: ≥6 weeks Serology: ++ Serology: + Serology: ++ Serology: ++ APR: Abnormal APR: Abnormal APR: Abnormal APR: Abnormal Yes Yes Yes Yes Yes No No No No No No No Yes Yes Yes Yes No Yes No Yes No Yes No Yes Duration: ≥6 weeks Serology: + Yes No No Yes Rheumatoid arthritis No classification of rheumatoid arthritis APR: Abnormal Example: False Positive Classification ≥6 = definite RA CASE SCENARIO Inflammatory Osteoarthritis One clinically inflamed OA joint (PIP 3 right hand) Tenderness of all DIPs, PIPs, thumb IPs, CMC 1, and knees Seronegative Long standing disease Normal acute phase If OA is clinically apparent, then this patient would not be in the target population of the criteria CASE SCENARIO Early seronegative RA Swollen and tender MCP 1-3 on both sides Seronegative 2 weeks duration Elevated CRP levels This patient might fulfill the criteria at a subsequent visit (be classified prospectively) Example: False Negative Classification ≥6 = definite RA
Slide 51 - 2010 ACR/EULAR Classification Criteria for Rheumatoid Arthritis Published in the September 2010 Issues of A&R and ARD Phases of the Project Phase 1 Data analysis Phase 2 Consensus process Phase 3 Integration of 1 and 2 Predictors of MTX initiation Final Criteria Determinants of high probability of RA Increase feasibility Phase 1 Data Driven Approach Phase 1: Patients and Methods Patients – EARLY ARTHRITIS COHORTS 3115 patients from 9 cohorts Inflammatory arthritis (no other definite diagnosis) of <3 years No previous DMARD/MTX treatment Methods – PREDICTORS OF MTX TREATMENT Step 1: Univariate regression analysis of all possible variables Step 2: Principal component analysis: identify themes Step 3: Multivariate regression analysis with all relevant themes Phase 1: Three Analytic Steps Univariate Regression Analysis Identify significant variables at baseline Gold standard: MTX treatment at one year STEP 1 STEPS 1 and 2: Predictors of MTX initiation Loadings: 0 – 0.199 0.2 – 0.399 0.4 – 0.599 0.6 – 0.799 0.8 – 1 STEP 2: Relevant Themes to Predict MTX Treatment Phase 1: Results Phase 1: Conclusion Swelling of small joint regions (PIP, MCP, wrist) has independent effect Tenderness might be also be considered as “joint involvement” Symmetrical involvement does not seem to have a significant incremental effect over unilateral involvement Abnormal acute phase response has a considerable effect Serology has a considerable effect, and shows a “dose-response” relationship of titres Phases of the Project Phase 1 Data analysis Phase 2 Consensus process Phase 3 Integration of 1 and 2 Predictors of MTX initiation Final Criteria Determinants of high probability of RA Increase feasibility Phase 2 Consensus Approach Phase 2: Methods Ranking of patient profiles by experts for their probability to develop RA Evidence based discussion on discrepancies in the ranking Specifying target population Developing positive and negative determinants for risk of RA (informed by Phase 1 data) Grouping these determinants into domains and categories Weighting of each category using decision analytic software Phase 2: Overview Expert panel Phase 2: Overview Expert panel Submit case scenarios of early undifferentiated inflammatory arthritis Phase 2: Overview Expert panel Specify target population Phase 2: Overview Expert panel Specify target population Positive factors + Negative factors - Discussion on reasons for discordance among physicians Phase 2: Overview Specify target population Positive factors + Negative factors - Discussion on reasons for discordance among physicians Phase 2: Results Phases of the Project Phase 1 Data analysis Phase 2 Consensus process Phase 3 Integration of 1 and 2 Predictors of MTX initiation Final Criteria Determinants of high probability of RA Increase feasibility Phase 3 Integration of Findings from Phases 1 and 2 Optimizing Feasibility Optimizing Feasibility Optimizing Feasibility Final Criteria Target Population of the Criteria Two requirements: (1) Patient with at least one joint with definite clinical synovitis (swelling) (2) Synovitis is not better explained by “another disease” Differential diagnoses differ in patients with different presentations. If unclear about the relevant differentials, an expert rheumatologist should be consulted. 2010 ACR/EULAR Classification Criteria for RA 2010 ACR/EULAR Classification Criteria for RA 2010 ACR/EULAR Classification Criteria for RA 2010 ACR/EULAR Classification Criteria for RA 2010 ACR/EULAR Classification Criteria for RA ≥6 = definite RA What if the score is <6? Patient might fulfill the criteria…  Prospectively over time (cumulatively)  Retrospectively if data on all four domains have been adequately recorded in the past Classification vs. Diagnosis We don’t have diagnostic criteria for RA Typically in rheumatic diseases, criteria are labeled as “classification” criteria These are helpful in defining homogeneous treatment populations for study purposes A clinical “diagnosis” has to be established by the physician (rheumatologist) It includes many more aspects than can be included in formal criteria Formal classification criteria might be a guide to establish a clinical diagnosis Classification vs. Diagnosis Algorithm to Classification of RA Including Radiographs Longstanding inactive disease suspected? ≥6/10 on the scoring system? Not RA RA No Radiographs already available Perform radiographic assessment Yes Erosions typical for RA present? Yes ≥1 swollen joint, which is not best explained by another disease? No No No Yes Document result of the scoring system Yes Yes No Summary: Radiographic Assessment WHEN TO PERFORM HOW TO USE The presence of typical erosions allow classification of RA even without fulfillment of the scoring system The scoring result should nevertheless be documented in clinical studies/trials Currently, there is no exact definition of “typical erosions” There is work in progress to develop the respective definitions GENERAL PRINCIPLES Radiographs are not required in the ACR/EULAR 2010 classification criteria Radiographs should not be taken for the mere purpose of classification EXCEPTIONS Radiographs should be taken in the unclassified patient in whom longstanding inactive disease is suspected (likely failed classification falsely) If radiographs are already available in an early arthritis patient, their information can be used for classification purposes. (e.g., radiographs taken by GP before referral) Definitions Definitions ≥6 = definite RA Definition of “JOINT INVOLVEMENT” Any swollen or tender joint (excluding DIP of hand and feet, 1st MTP, 1st CMC) Additional evidence from MRI / US may be used for confirmation of the clinical findings Definitions ≥6 = definite RA Definition of “SMALL JOINT” MCP, PIP, MTP 2-5, thumb IP, wrist NOT: DIP, 1st CMC, 1st MTP Definitions ≥6 = definite RA Definition of “LARGE JOINT” Shoulder, elbow, hip, knee, ankles ≥6 = definite RA Definition of “>10 JOINTS” At least one small joint Additional joints include: temporomandibular, sternoclavicular, acromioclavicular, and others (reasonably expected in RA) Definitions Definitions ≥6 = definite RA Definition of “SEROLOGY” Negative: ≤ULN (for the respective lab) Low positive: >ULN but ≤3xULN High positive: >3xULN Definitions ≥6 = definite RA Definition of “SYMPTOM DURATION” Refers to the patient’s self-report on the maximum duration of signs and symptoms of any joint that is clinically involved at the time of assessment. Algorithm for Classification Branch 4 Branch #1: Polyarticular Presentation Branch #2: Presentation with Oligo/Polyarticular Small Joints RA Branch #3: Presentation with Mono/Oligoarticular Small Joints Yes Branch #3: Presentation with Oligo/Polyarticular Large Joints START (eligible patient) RA RA RA RA RA RA RA RA >10 joints (at least one small joint) 4-10 small joints 1-3 small joints 2-10 large (no small) joints No No No Serology: +/++ Yes Yes No No No Yes Yes Duration: ≥6 weeks Duration: ≥6 weeks Duration: ≥6 weeks Duration: ≥6 weeks Serology: ++ Serology: + Serology: ++ Serology: ++ APR: Abnormal APR: Abnormal APR: Abnormal APR: Abnormal Yes Yes Yes Yes Yes No No No No No No No Yes Yes Yes Yes No Yes No Yes No Yes No Yes Duration: ≥6 weeks Serology: + Yes No No Yes Rheumatoid arthritis No classification of rheumatoid arthritis APR: Abnormal Example: False Positive Classification ≥6 = definite RA CASE SCENARIO Inflammatory Osteoarthritis One clinically inflamed OA joint (PIP 3 right hand) Tenderness of all DIPs, PIPs, thumb IPs, CMC 1, and knees Seronegative Long standing disease Normal acute phase If OA is clinically apparent, then this patient would not be in the target population of the criteria CASE SCENARIO Early seronegative RA Swollen and tender MCP 1-3 on both sides Seronegative 2 weeks duration Elevated CRP levels This patient might fulfill the criteria at a subsequent visit (be classified prospectively) Example: False Negative Classification ≥6 = definite RA Important Notes Criteria are classification criteria NOT diagnostic criteria In clinical practice they may inform the physician’s diagnosis For the purpose of classification, radiographs should only be performed For patients with longstanding inactive (“burnt out“) disease, who are NOT yet formally classified or diagnosed, and who would fail to classify as RA according to the scoring system, given their joint inactivity The term “erosions, typical for RA” still needs to be precisely defined (size, site, number) No exhaustive list of exclusions is defined Differential diagnosis is responsibility of the physician (influenced by age, gender, population, etc.) Limits false positive classification
Slide 52 - 2010 ACR/EULAR Classification Criteria for Rheumatoid Arthritis Published in the September 2010 Issues of A&R and ARD Phases of the Project Phase 1 Data analysis Phase 2 Consensus process Phase 3 Integration of 1 and 2 Predictors of MTX initiation Final Criteria Determinants of high probability of RA Increase feasibility Phase 1 Data Driven Approach Phase 1: Patients and Methods Patients – EARLY ARTHRITIS COHORTS 3115 patients from 9 cohorts Inflammatory arthritis (no other definite diagnosis) of <3 years No previous DMARD/MTX treatment Methods – PREDICTORS OF MTX TREATMENT Step 1: Univariate regression analysis of all possible variables Step 2: Principal component analysis: identify themes Step 3: Multivariate regression analysis with all relevant themes Phase 1: Three Analytic Steps Univariate Regression Analysis Identify significant variables at baseline Gold standard: MTX treatment at one year STEP 1 STEPS 1 and 2: Predictors of MTX initiation Loadings: 0 – 0.199 0.2 – 0.399 0.4 – 0.599 0.6 – 0.799 0.8 – 1 STEP 2: Relevant Themes to Predict MTX Treatment Phase 1: Results Phase 1: Conclusion Swelling of small joint regions (PIP, MCP, wrist) has independent effect Tenderness might be also be considered as “joint involvement” Symmetrical involvement does not seem to have a significant incremental effect over unilateral involvement Abnormal acute phase response has a considerable effect Serology has a considerable effect, and shows a “dose-response” relationship of titres Phases of the Project Phase 1 Data analysis Phase 2 Consensus process Phase 3 Integration of 1 and 2 Predictors of MTX initiation Final Criteria Determinants of high probability of RA Increase feasibility Phase 2 Consensus Approach Phase 2: Methods Ranking of patient profiles by experts for their probability to develop RA Evidence based discussion on discrepancies in the ranking Specifying target population Developing positive and negative determinants for risk of RA (informed by Phase 1 data) Grouping these determinants into domains and categories Weighting of each category using decision analytic software Phase 2: Overview Expert panel Phase 2: Overview Expert panel Submit case scenarios of early undifferentiated inflammatory arthritis Phase 2: Overview Expert panel Specify target population Phase 2: Overview Expert panel Specify target population Positive factors + Negative factors - Discussion on reasons for discordance among physicians Phase 2: Overview Specify target population Positive factors + Negative factors - Discussion on reasons for discordance among physicians Phase 2: Results Phases of the Project Phase 1 Data analysis Phase 2 Consensus process Phase 3 Integration of 1 and 2 Predictors of MTX initiation Final Criteria Determinants of high probability of RA Increase feasibility Phase 3 Integration of Findings from Phases 1 and 2 Optimizing Feasibility Optimizing Feasibility Optimizing Feasibility Final Criteria Target Population of the Criteria Two requirements: (1) Patient with at least one joint with definite clinical synovitis (swelling) (2) Synovitis is not better explained by “another disease” Differential diagnoses differ in patients with different presentations. If unclear about the relevant differentials, an expert rheumatologist should be consulted. 2010 ACR/EULAR Classification Criteria for RA 2010 ACR/EULAR Classification Criteria for RA 2010 ACR/EULAR Classification Criteria for RA 2010 ACR/EULAR Classification Criteria for RA 2010 ACR/EULAR Classification Criteria for RA ≥6 = definite RA What if the score is <6? Patient might fulfill the criteria…  Prospectively over time (cumulatively)  Retrospectively if data on all four domains have been adequately recorded in the past Classification vs. Diagnosis We don’t have diagnostic criteria for RA Typically in rheumatic diseases, criteria are labeled as “classification” criteria These are helpful in defining homogeneous treatment populations for study purposes A clinical “diagnosis” has to be established by the physician (rheumatologist) It includes many more aspects than can be included in formal criteria Formal classification criteria might be a guide to establish a clinical diagnosis Classification vs. Diagnosis Algorithm to Classification of RA Including Radiographs Longstanding inactive disease suspected? ≥6/10 on the scoring system? Not RA RA No Radiographs already available Perform radiographic assessment Yes Erosions typical for RA present? Yes ≥1 swollen joint, which is not best explained by another disease? No No No Yes Document result of the scoring system Yes Yes No Summary: Radiographic Assessment WHEN TO PERFORM HOW TO USE The presence of typical erosions allow classification of RA even without fulfillment of the scoring system The scoring result should nevertheless be documented in clinical studies/trials Currently, there is no exact definition of “typical erosions” There is work in progress to develop the respective definitions GENERAL PRINCIPLES Radiographs are not required in the ACR/EULAR 2010 classification criteria Radiographs should not be taken for the mere purpose of classification EXCEPTIONS Radiographs should be taken in the unclassified patient in whom longstanding inactive disease is suspected (likely failed classification falsely) If radiographs are already available in an early arthritis patient, their information can be used for classification purposes. (e.g., radiographs taken by GP before referral) Definitions Definitions ≥6 = definite RA Definition of “JOINT INVOLVEMENT” Any swollen or tender joint (excluding DIP of hand and feet, 1st MTP, 1st CMC) Additional evidence from MRI / US may be used for confirmation of the clinical findings Definitions ≥6 = definite RA Definition of “SMALL JOINT” MCP, PIP, MTP 2-5, thumb IP, wrist NOT: DIP, 1st CMC, 1st MTP Definitions ≥6 = definite RA Definition of “LARGE JOINT” Shoulder, elbow, hip, knee, ankles ≥6 = definite RA Definition of “>10 JOINTS” At least one small joint Additional joints include: temporomandibular, sternoclavicular, acromioclavicular, and others (reasonably expected in RA) Definitions Definitions ≥6 = definite RA Definition of “SEROLOGY” Negative: ≤ULN (for the respective lab) Low positive: >ULN but ≤3xULN High positive: >3xULN Definitions ≥6 = definite RA Definition of “SYMPTOM DURATION” Refers to the patient’s self-report on the maximum duration of signs and symptoms of any joint that is clinically involved at the time of assessment. Algorithm for Classification Branch 4 Branch #1: Polyarticular Presentation Branch #2: Presentation with Oligo/Polyarticular Small Joints RA Branch #3: Presentation with Mono/Oligoarticular Small Joints Yes Branch #3: Presentation with Oligo/Polyarticular Large Joints START (eligible patient) RA RA RA RA RA RA RA RA >10 joints (at least one small joint) 4-10 small joints 1-3 small joints 2-10 large (no small) joints No No No Serology: +/++ Yes Yes No No No Yes Yes Duration: ≥6 weeks Duration: ≥6 weeks Duration: ≥6 weeks Duration: ≥6 weeks Serology: ++ Serology: + Serology: ++ Serology: ++ APR: Abnormal APR: Abnormal APR: Abnormal APR: Abnormal Yes Yes Yes Yes Yes No No No No No No No Yes Yes Yes Yes No Yes No Yes No Yes No Yes Duration: ≥6 weeks Serology: + Yes No No Yes Rheumatoid arthritis No classification of rheumatoid arthritis APR: Abnormal Example: False Positive Classification ≥6 = definite RA CASE SCENARIO Inflammatory Osteoarthritis One clinically inflamed OA joint (PIP 3 right hand) Tenderness of all DIPs, PIPs, thumb IPs, CMC 1, and knees Seronegative Long standing disease Normal acute phase If OA is clinically apparent, then this patient would not be in the target population of the criteria CASE SCENARIO Early seronegative RA Swollen and tender MCP 1-3 on both sides Seronegative 2 weeks duration Elevated CRP levels This patient might fulfill the criteria at a subsequent visit (be classified prospectively) Example: False Negative Classification ≥6 = definite RA Important Notes Criteria are classification criteria NOT diagnostic criteria In clinical practice they may inform the physician’s diagnosis For the purpose of classification, radiographs should only be performed For patients with longstanding inactive (“burnt out“) disease, who are NOT yet formally classified or diagnosed, and who would fail to classify as RA according to the scoring system, given their joint inactivity The term “erosions, typical for RA” still needs to be precisely defined (size, site, number) No exhaustive list of exclusions is defined Differential diagnosis is responsibility of the physician (influenced by age, gender, population, etc.) Limits false positive classification Future Prospects 87-97% of patients started on MTX within one year were positively classified as RA in independent cohorts at baseline Formal external validation studies are ongoing Comparing proportions fulfilling ACR 1987 and ACR/EULAR 2010 criteria Identifying sensitivity, specificity, PPV, NPV etc. in independent settings
Slide 53 - 2010 ACR/EULAR Classification Criteria for Rheumatoid Arthritis Published in the September 2010 Issues of A&R and ARD Phases of the Project Phase 1 Data analysis Phase 2 Consensus process Phase 3 Integration of 1 and 2 Predictors of MTX initiation Final Criteria Determinants of high probability of RA Increase feasibility Phase 1 Data Driven Approach Phase 1: Patients and Methods Patients – EARLY ARTHRITIS COHORTS 3115 patients from 9 cohorts Inflammatory arthritis (no other definite diagnosis) of <3 years No previous DMARD/MTX treatment Methods – PREDICTORS OF MTX TREATMENT Step 1: Univariate regression analysis of all possible variables Step 2: Principal component analysis: identify themes Step 3: Multivariate regression analysis with all relevant themes Phase 1: Three Analytic Steps Univariate Regression Analysis Identify significant variables at baseline Gold standard: MTX treatment at one year STEP 1 STEPS 1 and 2: Predictors of MTX initiation Loadings: 0 – 0.199 0.2 – 0.399 0.4 – 0.599 0.6 – 0.799 0.8 – 1 STEP 2: Relevant Themes to Predict MTX Treatment Phase 1: Results Phase 1: Conclusion Swelling of small joint regions (PIP, MCP, wrist) has independent effect Tenderness might be also be considered as “joint involvement” Symmetrical involvement does not seem to have a significant incremental effect over unilateral involvement Abnormal acute phase response has a considerable effect Serology has a considerable effect, and shows a “dose-response” relationship of titres Phases of the Project Phase 1 Data analysis Phase 2 Consensus process Phase 3 Integration of 1 and 2 Predictors of MTX initiation Final Criteria Determinants of high probability of RA Increase feasibility Phase 2 Consensus Approach Phase 2: Methods Ranking of patient profiles by experts for their probability to develop RA Evidence based discussion on discrepancies in the ranking Specifying target population Developing positive and negative determinants for risk of RA (informed by Phase 1 data) Grouping these determinants into domains and categories Weighting of each category using decision analytic software Phase 2: Overview Expert panel Phase 2: Overview Expert panel Submit case scenarios of early undifferentiated inflammatory arthritis Phase 2: Overview Expert panel Specify target population Phase 2: Overview Expert panel Specify target population Positive factors + Negative factors - Discussion on reasons for discordance among physicians Phase 2: Overview Specify target population Positive factors + Negative factors - Discussion on reasons for discordance among physicians Phase 2: Results Phases of the Project Phase 1 Data analysis Phase 2 Consensus process Phase 3 Integration of 1 and 2 Predictors of MTX initiation Final Criteria Determinants of high probability of RA Increase feasibility Phase 3 Integration of Findings from Phases 1 and 2 Optimizing Feasibility Optimizing Feasibility Optimizing Feasibility Final Criteria Target Population of the Criteria Two requirements: (1) Patient with at least one joint with definite clinical synovitis (swelling) (2) Synovitis is not better explained by “another disease” Differential diagnoses differ in patients with different presentations. If unclear about the relevant differentials, an expert rheumatologist should be consulted. 2010 ACR/EULAR Classification Criteria for RA 2010 ACR/EULAR Classification Criteria for RA 2010 ACR/EULAR Classification Criteria for RA 2010 ACR/EULAR Classification Criteria for RA 2010 ACR/EULAR Classification Criteria for RA ≥6 = definite RA What if the score is <6? Patient might fulfill the criteria…  Prospectively over time (cumulatively)  Retrospectively if data on all four domains have been adequately recorded in the past Classification vs. Diagnosis We don’t have diagnostic criteria for RA Typically in rheumatic diseases, criteria are labeled as “classification” criteria These are helpful in defining homogeneous treatment populations for study purposes A clinical “diagnosis” has to be established by the physician (rheumatologist) It includes many more aspects than can be included in formal criteria Formal classification criteria might be a guide to establish a clinical diagnosis Classification vs. Diagnosis Algorithm to Classification of RA Including Radiographs Longstanding inactive disease suspected? ≥6/10 on the scoring system? Not RA RA No Radiographs already available Perform radiographic assessment Yes Erosions typical for RA present? Yes ≥1 swollen joint, which is not best explained by another disease? No No No Yes Document result of the scoring system Yes Yes No Summary: Radiographic Assessment WHEN TO PERFORM HOW TO USE The presence of typical erosions allow classification of RA even without fulfillment of the scoring system The scoring result should nevertheless be documented in clinical studies/trials Currently, there is no exact definition of “typical erosions” There is work in progress to develop the respective definitions GENERAL PRINCIPLES Radiographs are not required in the ACR/EULAR 2010 classification criteria Radiographs should not be taken for the mere purpose of classification EXCEPTIONS Radiographs should be taken in the unclassified patient in whom longstanding inactive disease is suspected (likely failed classification falsely) If radiographs are already available in an early arthritis patient, their information can be used for classification purposes. (e.g., radiographs taken by GP before referral) Definitions Definitions ≥6 = definite RA Definition of “JOINT INVOLVEMENT” Any swollen or tender joint (excluding DIP of hand and feet, 1st MTP, 1st CMC) Additional evidence from MRI / US may be used for confirmation of the clinical findings Definitions ≥6 = definite RA Definition of “SMALL JOINT” MCP, PIP, MTP 2-5, thumb IP, wrist NOT: DIP, 1st CMC, 1st MTP Definitions ≥6 = definite RA Definition of “LARGE JOINT” Shoulder, elbow, hip, knee, ankles ≥6 = definite RA Definition of “>10 JOINTS” At least one small joint Additional joints include: temporomandibular, sternoclavicular, acromioclavicular, and others (reasonably expected in RA) Definitions Definitions ≥6 = definite RA Definition of “SEROLOGY” Negative: ≤ULN (for the respective lab) Low positive: >ULN but ≤3xULN High positive: >3xULN Definitions ≥6 = definite RA Definition of “SYMPTOM DURATION” Refers to the patient’s self-report on the maximum duration of signs and symptoms of any joint that is clinically involved at the time of assessment. Algorithm for Classification Branch 4 Branch #1: Polyarticular Presentation Branch #2: Presentation with Oligo/Polyarticular Small Joints RA Branch #3: Presentation with Mono/Oligoarticular Small Joints Yes Branch #3: Presentation with Oligo/Polyarticular Large Joints START (eligible patient) RA RA RA RA RA RA RA RA >10 joints (at least one small joint) 4-10 small joints 1-3 small joints 2-10 large (no small) joints No No No Serology: +/++ Yes Yes No No No Yes Yes Duration: ≥6 weeks Duration: ≥6 weeks Duration: ≥6 weeks Duration: ≥6 weeks Serology: ++ Serology: + Serology: ++ Serology: ++ APR: Abnormal APR: Abnormal APR: Abnormal APR: Abnormal Yes Yes Yes Yes Yes No No No No No No No Yes Yes Yes Yes No Yes No Yes No Yes No Yes Duration: ≥6 weeks Serology: + Yes No No Yes Rheumatoid arthritis No classification of rheumatoid arthritis APR: Abnormal Example: False Positive Classification ≥6 = definite RA CASE SCENARIO Inflammatory Osteoarthritis One clinically inflamed OA joint (PIP 3 right hand) Tenderness of all DIPs, PIPs, thumb IPs, CMC 1, and knees Seronegative Long standing disease Normal acute phase If OA is clinically apparent, then this patient would not be in the target population of the criteria CASE SCENARIO Early seronegative RA Swollen and tender MCP 1-3 on both sides Seronegative 2 weeks duration Elevated CRP levels This patient might fulfill the criteria at a subsequent visit (be classified prospectively) Example: False Negative Classification ≥6 = definite RA Important Notes Criteria are classification criteria NOT diagnostic criteria In clinical practice they may inform the physician’s diagnosis For the purpose of classification, radiographs should only be performed For patients with longstanding inactive (“burnt out“) disease, who are NOT yet formally classified or diagnosed, and who would fail to classify as RA according to the scoring system, given their joint inactivity The term “erosions, typical for RA” still needs to be precisely defined (size, site, number) No exhaustive list of exclusions is defined Differential diagnosis is responsibility of the physician (influenced by age, gender, population, etc.) Limits false positive classification Future Prospects 87-97% of patients started on MTX within one year were positively classified as RA in independent cohorts at baseline Formal external validation studies are ongoing Comparing proportions fulfilling ACR 1987 and ACR/EULAR 2010 criteria Identifying sensitivity, specificity, PPV, NPV etc. in independent settings New classification criteria for RA have been established by an international task force Criteria are meant to be used for patients with clinical synovitis in at least one joint The classification criteria are not diagnostic criteria, but they can inform the diagnosis, which ultimately has to be made by the rheumatologist Validation in independent cohorts is already ongoing Summary