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Slide 53 -
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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
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