An evaluation of molecular and clinical remission in rheumatoid arthritis by assessing radiographic progression

Abstract

Objectives. To determine whether molecular remission defined by a multi-biomarker disease activity (MBDA) score predicts a reduced risk of joint damage progression, and whether the MBDA score can augment existing classifications of remission.Methods. The study examined 271 visits for 163 RA patients in the Leiden Early Arthritis Cohort. The MBDA score and other variables from each visit were evaluated for prediction of progression [change in Sharp–van der Heijde Score (ΔSHS) >3] over the ensuing 12 months. Positive likelihood ratios (PLRs) for non-progression were calculated for remission based upon DAS based on 28-joint counts and CRP (DAS28-CRP <2.32), EULAR/ACR Boolean criteria and MBDA score (≤25).Results. Ninety-three per cent of patients in MBDA-defined remission did not experience progression, compared with 70% of patients not in MBDA remission (P = 0.001). There were no significant differences in the fraction of non-progressers between patients in remission and those not in remission using either DAS28-CRP or EULAR/ACR criteria. The PLR for non-progression over 12 months for MBDA remission was 4.73 (95% CI 1.67, 15.0). Among patients in DAS28-CRP 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.Conclusion. MBDA-defined remission was an indicator of limited radiographic progression over the following 12 months. For patients in DAS28-CRP remission, high MBDA scores were a significant indicator of elevated risk of progression. MBDA results may provide a useful adjunct to clinical assessment to identify progression-free remission and assess subclinical disease.

A Multibiomarker Disease Activity Score for Rheumatoid Arthritis Predicts Radiographic Joint Damage in the BeSt Study

“…This might reflect the inclusion of inflammatory markers such as IL-6, and molecules relevant to bone and cartilage damage, such as YKL-40, MMP-1, and MMP-3, in the MBDA test. In a previous study, patients in DAS28-CRP remission were found to be at greater risk for progression of radiographic joint damage if they had a high MBDA score, and MBDA-defined remission was found to be a predictor for suppression of progressive joint damage 13 . The association of the MBDA score at Year 1 with radiological damage progression 1 year later is less strong, probably because after initiation of (DAS-steered) treatment, disease activity and damage progression are quite well suppressed.…”

Reanalysis of the Multi‐Biomarker Disease Activity Score for Assessing Disease Activity in the Abatacept Versus Adalimumab Comparison in Biologic‐Naive Rheumatoid Arthritis Subjects with Background Methotrexate Study: Comment on the Article by Fleischmann et al

“…Otherwise, the laboratory test would contain no incremental information beyond that offered by clinical evaluation. Several studies have shown that high MBDA scores were associated with radiographic progression and low scores with nonprogression (9-13), even when the patient was classified as having low disease activity or remission based on clinical measures (e.g., the DAS28-CRP) (9,12,20).…”

“…We would encourage readers to make the distinction between the scientific validity of a diagnostic test and its clinical utility. There is already a sizable evidence base supporting the development and validation of the MBDA test in diverse RA patient cohorts (9)(10)(11)(12)(13)(18)(19)(20)(23)(24)(25). A prospective clinical trial is underway to rigorously evaluate its clinical utility and its potential role in RA patient management (26).…”

Rheumatoid Arthritis: A Case for Personalized Health Care?

“…However, despite the presence of commercially available diagnostic assays, it remains controversial as to whether such testing offers sufficient predictive value to the direct selection of patients for continuing therapy (26). Last, a multimarker panel approach is being pursued aggressively by Crescendo Bioscience, using 12 different markers (27)(28)(29). While this may be predictive in smaller cohorts of samples already in part enriched for responders, additional tailoring of markers and algorithms may be needed to deliver a meaningful result in clinical practice.…”