Abstract
ObjectivesTo systematically review the impact of tapering targeted therapies (bDMARDs or JAKis) on the risk of serious infections and severe adverse events (SAEs) in patients with rheumatoid arthritis (RA) or axial spondyloarthritis (axSpA) in remission or low disease activity (LDA) state.Materials and methodsA meta-analysis based on a systematic review of PubMed, Embase, Cochrane, until August 2019, as well as relevant databases of international conferences, was used to evaluate the risk difference (RD) at 95% confidence interval (95% CI) of incidence density of serious infections, SAEs, malignancies, cardiovascular adverse events (CV AEs), or deaths after tapering (dose reduction or spacing) compared to continuation of targeted therapies.ResultsOf the 1957 studies initially identified, 13 controlled trials (9 RA and 4 SpA trials) were included in the meta-analysis. 1174 patient-years were studied in the tapering group (TG) versus 1086 in the usual care group (UC). There were 1.7/100 patient-year (p-y) serious infections in TG versus 2.6/100 p-y in UC (RD (95% CI) 0.01 (0.00 to 0.02), p = 0.13) and 7.4/100 p-y SAEs in TG versus 6.7/100 p-y in UC (RD 0.00 (− 0.02 to 0.02), p = 0.82). The risk of malignancies, CV AEs, or deaths did not differ between the tapering and the usual care groups. Subgroup analysis (RA and SpA) detected no significant differences between the two groups.ConclusionWe could not show significant impact of tapering bDMARD or JAKi over continuation concerning the risk of serious infections, SAEs, malignancies, CV AEs, or deaths in RA and SpA patients in remission or LDA state.
Highlights
Current best practice in the treatment of chronic inflammatory rheumatisms such as rheumatoid arthritis (RA) and spondyloarthritis (SpA) focusses on a tight control strategy to prevent joint destruction and improve patients’ functional prognosis
The first-line treatment for RA consists of conventional synthetic disease-modifying anti-rheumatic drugs [3], whereas initial treatment for SpA is based on non-steroidal anti-inflammatory drugs (NSAIDs) [4, 5]
The title and abstract of articles identified from database searches were subsequently reviewed for the following inclusion criteria: (1) controlled trials, randomized or not; (2) involving rheumatoid arthritis (RA) or spondyloarthritis (SpA) patients; (3) treated by targeted therapies: Biological DMARDs (bDMARDs) (anti-TNF or abatacept or anti-IL6 or rituximab or anti IL 12/23 or anti IL 17 or anti-IL 23) or JAKis; (4) in remission or low disease activity (LDA) under targeted therapies; and (5) comparing tapering targeted therapies (tapering group (TG)) versus continuation of the initial treatment regimen (usual care group (UC))
Summary
Current best practice in the treatment of chronic inflammatory rheumatisms such as rheumatoid arthritis (RA) and spondyloarthritis (SpA) focusses on a tight control strategy (treat-to-target strategy) to prevent joint destruction and improve patients’ functional prognosis. The first-line treatment for RA consists of conventional synthetic disease-modifying anti-rheumatic drugs (csDMARDs) [3], whereas initial treatment for SpA is based on non-steroidal anti-inflammatory drugs (NSAIDs) [4, 5] Thereafter, in both diseases, biological DMARDs (bDMARDS) are employed, and the use of bDMARDs and more recently targeted synthetic DMARDs (tsDMARDs) has been part of the clear improvement in the therapeutic management of these diseases, leading to sustained LDA or remission in a large number of patients [6, 7]. The European League Against Rheumatisms (EULAR) and the American College of Rheumatology (ACR) have addressed these issues by publishing recommendations for the management of chronic inflammatory rheumatisms once remission or LDA has been established, based on a tapering strategy [3,4,5, 16,17,18]
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