A multi-biomarker disease activity score can predict sustained remission in rheumatoid arthritis

D L Scott,A P Cope,E H Sasso,N Defranoux,W Li,M H Y Ma,F Ibrahim

doi:10.1186/s13075-020-02240-w

Abstract

BackgroundReliable assessment of remission is important for the optimal management of rheumatoid arthritis (RA) patients. In this study, we used the multi-biomarker disease activity (MBDA) test to explore the role of biomarkers in predicting point remission and sustained remission.MethodsRA patients on > 6 months stable therapy in stable low disease activity (DAS28-ESR ≤ 3.2) were assessed every 3 months for 1 year. Baseline, intermittent (IR) and sustained (SR) remission were defined by DAS28-ESR, DAS28-CRP, simple disease activity index (SDAI), clinical disease activity index (CDAI) and ACR/EULAR Boolean criteria. Patients not fulfilling any remission criteria at baseline were classified as ‘low disease activity state’ (LDAS). Patients not fulfilling any remission criteria over 1 year were classified as ‘persistent disease activity’ (PDA). MBDA score was measured at baseline/3/6 months. The baseline MBDA score, the 6-month time-integrated MBDA score and MBDA biomarkers were used for analyses. The area under the receiver operating characteristic curve (AUROC) assessed the ability of the MBDA score to discriminate between remission and non-remission. Biomarkers were analysed at baseline using the Mann-Whitney test and over time using the Jonckheere-Terpstra trend test.ResultsOf 148 patients, 27% were in the LDAS, 65% DAS28-ESR remission, 51% DAS28-CRP remission, 40% SDAI remission, 43% CDAI remission and 25% ACR/EULAR Boolean remission at baseline. Over 1 year, 9% of patients were classified as PDA. IR and SR were achieved in 42%/47% by DAS28-ESR, 46%/29% by DAS28-CRP, 45%/20% by SDAI, 44%/21% by CDAI and 35%/9% by ACR/EULAR Boolean criteria, respectively. By all remission criteria, baseline MBDA score discriminated baseline remission (AUROCs 0.68–0.75) and IR/SR (AUROCs 0.65–0.74). The 6-month time-integrated MBDA score discriminated IR/SR (AUROCs 0.65–0.79). Baseline MBDA score and concentrations of IL-6, leptin, SAA and CRP were significantly lower in all baseline remission criteria groups vs LDAS. They and the 6-month time-integrated values were lower among patients who achieved IR/SR vs PDA over 1 year.ConclusionsThis study demonstrated that the MBDA score and its biomarkers IL-6, leptin, SAA and CRP differentiated between small differences in disease activity (i.e. between low disease activity and remission states). They were also predictors of remission over 1 year.

Highlights

Rheumatoid arthritis (RA) is a chronic disease with heterogeneous outcomes
This study demonstrated that the multi-biomarker disease activity (MBDA) score and its biomarkers IL-6, leptin, Serum amyloid-A (SAA) and C-reactive protein (CRP) differentiated between small differences in disease activity
Patient cohort Serum samples were available for 148 patients from the Remission in RA Study (REMIRA) cohort

Summary

Introduction

Rheumatoid arthritis (RA) is a chronic disease with heterogeneous outcomes. Early treatment intervention, biologic therapies, and tight control treatment strategies have made achievement of low disease-activity, including remission states, increasingly common [1]. The remission criteria that have evolved over the last two decades reflect a common underlying theme. These criteria include measurement of clinical variables assessed by clinicians and patients, such as joint counts and global scores, as well as inflammatory blood markers, such as the erythrocyte sedimentation rate (ESR) or C-reactive protein (CRP). Flares can occur when DMARDs are tapered or stopped for patients in low disease activity or clinical remission [12]. These findings indicate that a subset of patients in clinical remission have clinically significant disease despite displaying few clinical signs or symptoms. We used the multi-biomarker disease activity (MBDA) test to explore the role of biomarkers in predicting point remission and sustained remission

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