Prediction of flare following remission and treatment withdrawal in early rheumatoid arthritis: post hoc analysis of a phase IIIb trial with abatacept

Harris A Ahmad,Paul Emery,Thomas W J Huizinga,Yedid Elbez,Philip G Conaghan,Subhashis Banerjee,Joshua F Baker,Mikkel Østergaard

doi:10.1186/s13075-022-02735-8

Abstract

BackgroundDrug-free remission is a desirable goal in rheumatoid arthritis (RA) for both patients and clinicians. The aim of this post hoc analysis was to investigate whether clinical and magnetic resonance imaging (MRI) variables in patients with early RA who achieved remission with methotrexate and/or abatacept at 12 months could predict disease flare following treatment withdrawal.MethodsIn the AVERT study of abatacept in early RA, patients with low disease activity at month 12 entered a 12-month period with all treatment discontinued (withdrawal, WD). This post hoc analysis assessed predictors of disease flare at WD+6months (mo) and WD+12mo of patients with Disease Activity Score in 28 joints (DAS28)-defined remission (DAS28[C-reactive protein (CRP)] <2.6) at withdrawal using univariate and multivariable regression models. Predictors investigated included the Health Assessment Questionnaire–Disability Index (HAQ-DI), pain, Patient Global Assessment; MRI synovitis, erosion, bone edema, and combined (synovitis + bone edema) inflammation scores.ResultsRemission was achieved by 172 patients; 100 (58%) and 113 (66%) patients had experienced a flare at WD+6mo and WD+12mo, respectively. In univariate analyses, higher HAQ-DI and MRI synovitis, erosion, bone edema, and combined inflammation scores at WD were identified as potential predictors of flare (P ≤ 0.01). In multivariable analysis, high scores at WD for HAQ-DI and MRI erosion were confirmed as independent predictors of flare at WD+6mo and WD+12mo (P < 0.01).ConclusionIn patients with early RA achieving clinical remission, patient function (HAQ-DI), and MRI measures of bone damage (erosion) predicted disease flare 6 and 12 months after treatment withdrawal. These variables may help identify patients with early RA in clinical remission as candidates for successful treatment withdrawal.Trial registrationClinicalTrials.gov, NCT01142726 (date of registration: June 11, 2010)

Highlights

Drug-free remission is a desirable goal in rheumatoid arthritis (RA) for both patients and clinicians
The tapering or discontinuation of bDMARDs is often recommended in patients with sustained remission [4], complete withdrawal of RA therapy may be possible in some patients without inducing disease flares
Data were available for 172 patients with Disease Activity Score in 28 joints (DAS28)(CRP)defined remission at WD across the three treatment arms

Summary

Introduction

Drug-free remission is a desirable goal in rheumatoid arthritis (RA) for both patients and clinicians. The aim of this post hoc analysis was to investigate whether clinical and magnetic resonance imaging (MRI) variables in patients with early RA who achieved remission with methotrexate and/or abatacept at 12 months could predict disease flare following treatment withdrawal. Treatment of RA with disease-modifying antirheumatic drugs (DMARDs) is recommended to reduce inflammation, relieve symptoms, and halt or minimize structural progression that may lead to disability [3,4,5]. The tapering or discontinuation of bDMARDs is often recommended in patients with sustained remission [4], complete withdrawal of RA therapy may be possible in some patients without inducing disease flares. Data for biomarkers as predictive tools are conflicting [10] and data for physician- and patientreported measures are lacking

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