Tapering bDMARDs May Help Sustain RA Remission

Janis C. Kelly

December 13, 2017

In patients with rheumatoid arthritis (RA) who are receiving biological disease-modifying antirheumatic drugs (bDMARDs) and in remission, relapse is less likely when bDMARDs are tapered rather than discontinued, a systematic literature analysis and meta-analysis found.

Current RA guidelines recommend decreasing or stopping bDMARDs once a patient has achieved stable remission or low disease activity (LDA), but the question of how to do this safely is still under discussion.

Sophie Henauz, MD, and colleagues from Hôpital Purpan in Toulouse, France, approached this problem using a systematic literature analysis plus meta-analysis to compare outcomes for discontinuing or tapering bDMARDs and continuing bDMARDs in patients with RA in remission or at LDA status.

They published their findings online November 29 in the Annals of the Rheumatic Diseases.

The authors conclude that risk of losing remission or risk for relapse from a state of LDA was lower in patients whose bDMARD doses were tapered than in those whose bDMARDs were discontinued. They write, "discontinuation of bDMARDs leads to an increased risk of losing remission or LDA and radiographic progression, while tapering doses of bDMARDs does not increase the risk of relapse (LDA) or radiographic progression, even though there is an increased risk of losing remission."

Arthur F. Kavanaugh, MD, who was not involved in the study, told Medscape Medical News, "I don't think many would disagree with the conclusion that tapering treatment is likely better than stopping it completely, in terms of disease activity. The crucial point for clinicians is that these are group-level data. There are patients who stop treatment and remain in remission for years and have no X-ray progression, and there are patients who taper who flare and have X-ray progression. So this doesn't really provide strong guidance for what to do with individual patients." Dr Kavanaugh is a professor of clinical medicine and director, Center for Innovative Therapy, University of California, San Diego, School of Medicine.

The authors carried a systematic analysis of the literature through May 2017, looking for prospective controlled trials that included reducing or discontinuing bDMARDs (except for rituximab) in patients with RA that was in stable remission (disease activity score on 28 joints [DAS28]-erythrocyte sedimentation rate [ESR] <2.6) or in a state of LDA (DAS28-ESR <3.2). Studies did not have to be randomized.

Selection criteria included comparing bDMARD tapering (via dose reduction or spacing, according to European League Against Rheumatism criteria) with continuation of the original treatment regimen. Study endpoints included at least one of the following: evidence of flare, loss of remission, loss of LDA, or structural progression defined by total Sharp score progression of at least 0.5. The researchers excluded rituximab studies "because of the wide range of retreatment protocols available for this particular bDMARD." Other exclusion criteria included trials that did not include a continuation group or trials in which the bDMARD regimen was changed for a reason other than achieving remission or LDA.

The literature review identified 13 published articles and four abstracts for analysis. This included 1054 patients who continued bDMARDs and 766 who discontinued bDMARDs. The monitoring period was 1 year. Among the studies of bDMARD tapering, 755 patients continued bDMARDs and 835 patients reduced bDMARD doses.

Discontinuing bDMARDs roughly doubled the risk of losing remission or LDA status compared with continuing bDMARDs (risk ratio [RR], 1.97 [P < .0001] and 2.24 [P < .0001], respectively). Discontinuing bDMARDs was also associated with an increased risk for radiographic progression (RR, 1.09; P = .01).

Tapering bDMARDs appeared somewhat less risky. The meta-analysis comparing bDMARD tapering with bDMARD continuation showed an increased risk of losing remission (RR, 1.23; P = .006), but no increased risk of relapsing from LDA (RR, 1.02; P = .81). Tapering was also not associated with increased risk for radiographic progression (RR, 1.09; P = .26).

The authors conclude, "Our meta-analysis reveals that, in RA patients with remission or LDA, discontinuation of bDMARDs leads to an increased risk of losing remission or LDA and radiographic progression, while tapering doses of bDMARDs does not increase the risk of relapse (LDA) or radiographic progression, even though there is an increased risk of losing remission, in comparison with continuation of the initial bDMARD regimen. Given the increased risk of infections attributable to the higher doses and the direct cost of bDMARDs, a dose reduction strategy (lowering or spacing doses) appears to be a reasonable option for patients with RA in stable remission or LDA."

Dr Kavanaugh noted one major problem with the meta-analysis, however: "Methodologically, they violate a cardinal rule of meta-analyses; namely, to combine data from different studies, the individual trials need to be similar and without important differences. On this topic, there are so many crucial variables that could affect the outcome that it is absolutely untenable to mix them all into a single meta-analysis," he said.

Abbott provided logistic support in the organization of the sessions and about implementation of a meta-analysis. The authors and Dr Kavanaugh have disclosed no relevant financial relationships.

Ann Rheum Dis. Published online November 29, 2017. Abstract

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