Background Useful definitions of remission in rheumatoid arthritis (RA) should identify patients at reduced risk of progressive joint damage. A novel multi-biomarker test for disease activity (MBDA) in RA was recently developed and validated.
Objectives 1) To determine whether molecular remission as defined by the MBDA score predicts a reduced risk of joint progression and 2) to evaluate whether the MBDA test can augment existing classifications of remission.
Methods Subjects were 163 members of the Leiden Early Arthritis Cohort who met the 1987 ACR criteria for RA. The pre-specified MBDA algorithm combined the concentrations of 12 biomarkers to produce scores from 1-100. MBDA score and other variables were assessed at 271 study visits and evaluated for prediction of progression over the following 12 months. For the primary analysis, subjects with change in Sharp-van der Heijde Score (ΔSHS) ≤3 were classified as non-progressors. The pre-test odds, post-test odds and positive likelihood ratios for non-progression were calculated for definitions of remission based upon DAS28CRP (<2.32), EULAR/ACR Boolean criteria, or MBDA score (≤25).
Results The percentages of patient visits representing remission were 11% by ACR/EULAR Boolean criteria, 16% by MBDA score criteria and 31% by DAS28-CRP criteria. Among 32 visits at which patients were in MBDA score remission but not ACR/EULAR remission, 30 failed to meet the ACR/EULAR criteria because of patient global assessment, 13 because of TJC, 4 because of SJC and 2 because of CRP. Note that there could be multiple reasons for a patient not meeting the ACR/EULAR criteria. However, in 17 of the 32 cases, the patient global assessment criterion was the only one not satisfied.
The positive likelihood ratio (PLR) for non-progression over 12 months for MBDA remission was 4.73 (95% CI = [1.67, 15.0]). PLRs were greater than 1 but not statistically significant for DAS28CRP <2.32 (PLR =1.38; 95% CI = [0.90, 2.38]) and the EULAR/ACR Boolean criteria (PLR =1.78; 95% CI = [0.72, 5.17]). For patients in DAS28CRP remission, those with a high MBDA score were 2.3 times as likely (95% CI = [1.1, 3.7]) to have joint damage progression during the next year. Similar relative performance was observed using other ΔSHS thresholds for non-progression.
Conclusions In a cohort of early arthritis patients, MBDA-defined remission was an indicator of limited radiographic progression over the following 12 months. Elevated patient global assessment was the most common reason for patients failing to meet ACR/EULAR Boolean remission criteria when in MBDA remission. Among patients in DAS28CRP remission, high MBDA scores identify those at elevated risk of progression. MBDA results may provide a useful adjunct to clinical assessment to identify progression-free remission.
Disclosure of Interest A. van der Helm-van Mil: None Declared, R. Knevel: None Declared, F. Qureshi Employee of: Crescendo Bioscience, W. Manning Employee of: Crescendo Bioscience, G. Cavet Employee of: Crescendo Bioscience, T. Huizinga Consultant for: Crescendo Bioscience, D. Haney Employee of: Crescendo Bioscience