Predicting drug-free remission in rheumatoid arthritis: A prospective interventional cohort study

Kenneth F Baker,Andrew J Skelton,Dennis W Lendrem,Adam Scadeng,Ben Thompson,Arthur G Pratt,John D Isaacs

doi:10.1016/j.jaut.2019.06.009

Abstract

BackgroundMany patients with rheumatoid arthritis (RA) achieve disease remission with modern treatment strategies. However, having achieved this state, there are no tests that predict when withdrawal of therapy will result in drug-free remission rather than flare. We aimed to identify predictors of drug-free remission in RA. MethodsThe Biomarkers of Remission in Rheumatoid Arthritis (BioRRA) Study was a unique, prospective, interventional cohort study of complete and abrupt cessation of conventional synthetic disease-modifying anti-rheumatic drugs (DMARDs). Patients with RA of at least 12 months duration and in clinical and ultrasound remission discontinued DMARDs and were monitored for six months. The primary outcome was time-to-flare, defined as disease activity score in 28 joints with C-reactive protein (DAS28-CRP) ≥ 2.4. Baseline clinical and ultrasound measures, circulating inflammatory biomarkers, and peripheral CD4+ T cell gene expression were assessed for their ability to predict time-to-flare and flare/remission status by Cox regression and receiver-operating characteristic (ROC) analysis respectively. Results23/44 (52%) eligible patients experienced an arthritis flare after a median (IQR) of 48 (31.5–86.5) days following DMARD cessation. A composite score incorporating five baseline variables (three transcripts [FAM102B, ENSG00000228010, ENSG00000227070], one cytokine [interleukin-27], one clinical [Boolean remission]) differentiated future flare from drug-free remission with an area under the ROC curve of 0.96 (95% CI 0.91–1.00), sensitivity 0.91 (0.78–1.00) and specificity 0.95 (0.84–1.00). ConclusionWe provide proof-of-concept evidence for predictors of drug-free remission in RA. If validated, these biomarkers could help to personalize immunosuppressant withdrawal: a therapy paradigm shift with ensuing patient and economic benefits.

Highlights

The past two decades have witnessed a remarkable revolution in rheumatoid arthritis (RA) outcomes, from a disease of inexorable joint destruction and disability to one where sustained remission is a realistic and achievable treatment target [1]
We present the findings of a prospective interventional study of complete cessation of conventional synthetic disease-modifying antirheumatic drugs (DMARDs) in patients with RA in stable remission
78 patients attended for baseline assessment, of which 44 patients were eligible for DMARD cessation (Fig. 1)

Summary

Introduction

The past two decades have witnessed a remarkable revolution in rheumatoid arthritis (RA) outcomes, from a disease of inexorable joint destruction and disability to one where sustained remission is a realistic and achievable treatment target [1]. Many of these advances have been realised through the effective use of disease-modifying antirheumatic drugs (DMARDs), especially their initiation in the early phases of disease and escalation in a treat-to-target fashion [2]. Conclusion: We provide proof-of-concept evidence for predictors of drug-free remission in RA If validated, these biomarkers could help to personalize immunosuppressant withdrawal: a therapy paradigm shift with ensuing patient and economic benefits

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