Efficacy of pharmacological treatment in rheumatoid arthritis: a systematic literature research informing the 2019 update of the EULAR recommendations for management of rheumatoid arthritis

Abstract

Objectives: To inform the 2019 update of the European League against Rheumatism (EULAR) recommendations for the management of rheumatoid arthritis (RA).

Methods: A systematic literature research (SLR) to investigate the efficacy of any disease-modifying antirheumatic drug (DMARD) (conventional synthetic (cs)DMARD, biological (b) and biosimilar DMARD, targeted synthetic (ts)DMARD) or glucocorticoid (GC) therapy in patients with RA was done by searching MEDLINE, Embase and the Cochrane Library for articles published between 2016 and 8 March 2019.

Results: 234 abstracts were selected for detailed assessment, with 136 finally included. They comprised the efficacy of bDMARDs versus placebo or other bDMARDs, efficacy of Janus kinase (JAK) inhibitors (JAKi) across different patient populations and head-to-head of different bDMARDs versus JAKi or other bDMARDs. Switching of bDMARDs to other bDMARDs or tsDMARDs, strategic trials and tapering studies of bDMARDs, csDMARDs and JAKi were assessed. The drugs evaluated included abatacept, adalimumab, ABT-122, baricitinib, certolizumab pegol, SBI-087, CNTO6785, decernotinib, etanercept, filgotinib, golimumab, GCs, GS-9876, guselkumab, hydroxychloroquine, infliximab, leflunomide, mavrilimumab, methotrexate, olokizumab, otilimab, peficitinib, rituximab, sarilumab, salazopyrine, secukinumab, sirukumab, tacrolimus, tocilizumab, tofacitinib, tregalizumab, upadacitinib, ustekinumab and vobarilizumab. The efficacy of many bDMARDs and tsDMARDs was shown. Switching to another tumour necrosis factor inhibitor (TNFi) or non-TNFi bDMARDs after TNFi treatment failure is efficacious. Tapering of DMARDs is possible in patients achieving long-standing stringent clinical remission; in patients with residual disease activity (including patients in LDA) the risk of flares is increased during the tapering. Biosimilars are non-inferior to their reference products.

Conclusion: This SLR informed the task force regarding the evidence base of various therapeutic regimen for the development of the update of EULAR's RA management recommendation.

Keywords: DMARDs (biologic); DMARDs (synthetic); anti-TNF; rheumatoid arthritis.

Figure 1

PRISMA flow chart describing the study selection process. DMARDs, disease-modifying antirheumatic drugs; PRISMA, Preferred Reporting Items for Systematic Reviews and Meta-Analyses; SLR, systematic literature research.

Figure 2

Forest plots showing risk ratios of ACR 20, 50 and 70 responses in trials comparing JAK inhibitors+MTX to adalimumab +MTX in MTX-IR patients. 1, tofacitinib; 2, upadacitinib; 3, baricitinib. ACR, American College of Rheumatology; IR, insufficient responder; M-H, Mantel-Haenszel; MTX, methotrexate; JAK, Janus kinase.

Figure 3

Efficacy of different targets of biological and targeted synthetic disease-modifying drugs compared against placebo, shown across major clinical trial outcomes of randomised controlled trials published from 2016 to 2018. ACR, American College of Rheumatology response criteria; CD, cluster of differentiation; DMARD, disease-modifying antirheumatic drugs; EULAR, European League against Rheumatism; GM-CSF, colony-stimulating factor; HAQ, Health Assessment Questionnaire; IL, interleukin; JAK, Janus kinase; mTSS, modified total Sharp score; Syk, spleen tyrosine kinase; TNF, tumour necrosis factor.