The effect of deep or sustained remission on maintenance of remission after dose reduction or withdrawal of etanercept in patients with rheumatoid arthritis

Josef S. Smolen,Paul Emery,Lisa Marshall,Annette Szumski,Yoshiya Tanaka,Heather Jones

doi:10.1186/s13075-019-1937-4

Abstract

BackgroundBiologic disease-modifying antirheumatic drugs (bDMARDs) are important options for managing rheumatoid arthritis (RA). Once patients achieve disease control, clinicians may consider dose reduction or withdrawal of the bDMARD. Results from published studies indicate that some patients will maintain remission; however, others will flare. We analyzed data from three etanercept down-titration studies in patients with RA to determine what extent of remission provides the greatest predictability of maintaining remission following dose reduction or discontinuation.MethodsPatients with moderate to severe RA from the PRESERVE, PRIZE, and Treat-to-Target (T2T) randomized controlled trials were included. We determined the proportion of patients achieving remission with etanercept at the last time point in the induction period, and sustained remission (last two time points), according to the Disease Activity Score 28-joints (DAS28), the American College of Rheumatology (ACR)/European League Against Rheumatism (EULAR) Boolean criteria, and the clinical disease activity index (CDAI). We also calculated the proportion achieving DAS28 deep remission (DAS28 ≤ 1.98), sustained deep remission (last two time points), and low disease activity (LDA), and LDA according to the CDAI. Then, we evaluated whether they maintained remission or LDA following etanercept dose reduction or withdrawal.ResultsPatients achieving sustained and/or deep remission were more likely than patients achieving remission or LDA to maintain remission/LDA after etanercept dose reduction or withdrawal. In PRESERVE, the proportions of patients with DAS28 sustained deep remission, deep remission, sustained remission, remission, and LDA who maintained remission following etanercept dose reduction were 81%, 67%, 58%, 56%, and 36%, respectively, P < 0.001 for trend. In PRESERVE, this trend was significant when etanercept was discontinued and when ACR/EULAR Boolean and CDAI remission criteria were used. Although some sample sizes were small, the PRIZE and T2T studies also demonstrated response trends according to ACR/EULAR Boolean and CDAI remission criteria, and T2T demonstrated response trends according to DAS28.ConclusionsThese results suggest that patients achieving disease control according to a stringent definition, such as sustained ACR/EULAR Boolean or CDAI remission, or a new definition of sustained deep remission by DAS28, have a higher probability of remaining in remission or LDA following etanercept dose reduction or withdrawal.Trial registrationPRESERVE: ClinicalTrials.gov identifier: NCT00565409, registered 30 November 2007; PRIZE: ClinicalTrials.gov identifier: NCT00913458, registered 4 June 2009; T2T: ClinicalTrials.gov identifier: NCT01578850, registered 17 April 2012

Highlights

Biologic disease-modifying antirheumatic drugs are important options for managing rheumatoid arthritis (RA)
Studies have required patients to have low disease activity (LDA) according to Disease Activity Score 28-joint count (DAS28 ≤ 3.2) for 6 months [17, 18] or Disease Activity Score 28-joints (DAS28) remission (DAS28 < 2.6) for 6 months [19, 20] or 12 months [21], LDA according to DAS28 or clinician judgment for 3 months [22, 23], moderate to good European League Against Rheumatism (EULAR) response at month 6 [24], or remission according to the clinical disease activity index (CDAI) at month 6 [25]
Clinical response in period 1 and baseline characteristics according to clinical response This analysis includes 600, 598, and 594 patients in the American College of Rheumatology (ACR)/EULAR Boolean, CDAI, and DAS28 remission criteria calculations, respectively, from the PRESERVE study; 193, 192, and 192 patients, respectively, from the PRIZE study; and 331 patients in all three remission criteria calculations from the T2T study

Summary

Introduction

Biologic disease-modifying antirheumatic drugs (bDMARDs) are important options for managing rheumatoid arthritis (RA). Once patients achieve disease control, clinicians may consider dose reduction or withdrawal of the bDMARD. Treatment guidelines for rheumatoid arthritis (RA) recommend intensive therapy targeting clinical remission early in the disease course, when patients have a higher likelihood of responding to treatment [1,2,3,4,5]. This treatment target has been shown to correlate with better patient-reported outcomes, greater productivity, and lower overall healthcare costs than achieving low disease activity (LDA) [6, 7]. Studies have required patients to have LDA according to Disease Activity Score 28-joint count (DAS28 ≤ 3.2) for 6 months [17, 18] or DAS28 remission (DAS28 < 2.6) for 6 months [19, 20] or 12 months [21], LDA according to DAS28 or clinician judgment for 3 months [22, 23], moderate to good European League Against Rheumatism (EULAR) response at month 6 [24], or remission according to the clinical disease activity index (CDAI) at month 6 [25]

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