Efficacy and safety of biologic, biosimilars and targeted synthetic DMARDs in moderate-to-severe rheumatoid arthritis with inadequate response to methotrexate: a systematic review and network meta-analysis

Abstract

Objective: To assess the comparative efficacy and safety of approved biologic disease-modifying antirheumatic drugs (bDMARDs), biosimilars, and targeted synthetic disease-modifying antirheumatic drugs (tsDMARDs) for patients with rheumatoid arthritis (RA) who had inadequate responses to methotrexate (MTX). Results: 53 eligible studies were identified and 44 studies were included in a network meta-analysis. Using Surface Under the Cumulative Ranking Curve (SUCRA), tofacitinib (10 mg bid) with MTX [Relative risk (RR) 95% confidence interval (CI) 4.65 (2.98-7.27)] and tofacitinib (10 mg bid) [RR (95%CI)1.96 (1.27-3.03)] were ranked highest among tsDMARDs for increasing remission rate at 24-26 weeks and 48-52 weeks, respectively. For bDMARDs, tocilizumab (8 mg/kg) with MTX was ranked with highest treatment effect for remission at both 24-26 and 48-52 weeks [RR (95%CI) 3.06 (2.27-4.12); RR (95%CI) 2.52 (1.94-3.28)]. For safety, baricitinib (4 mg) and tofacitinib (5 mg bid) with MTX likely showed an increased risk of HZ with statistical significance [for baricitinib, RR (95%CI) 3.52 (1.38-9.02) at 24-26 weeks, and RR (95%CI) 4.20 (1.22-14.48) at 48-52 weeks, and for tofacitinib, RR (95%CI) 5.38 (1.00-28.91) at 48-52 weeks]. No statistically significant safety concerns for serious infection, tuberculosis (TB), cancer, and cardiovascular (CV) events were identified. Conclusions: For RA patients who failed MTX, bDMARDs, biosimilars, and tsDMARDs monotherapy and combination therapy with MTX provided better treatment outcomes than MTX monotherapy with modest safety concerns within 24-52 weeks. A scarcity of longer-term effects and post-market surveillance necessitates further analyses using long-term patient-level data to improve the medication profile. Keywords: Antirheumatic Agents, Arthritis, Rheumatoid with inadequate responses to conventional synthetic DMARDs, serious adverse events, network meta-analysis

Cost-utility analysis of biologic disease-modifying antirheumatic drugs (bDMARD), targeted synthetic DMARD (tsDMARD) and biosimilar DMARD (bsDMARD) combined with methotrexate for Thai rheumatoid arthritis patients with high disease activity

“…A systematic review and network meta-analysis (SR-NMA) were used to assess the treatment effects and safety of bDMARD, tsDMARD, and their biosimilars at 6, 12, and 24 months, and full details of SR-NMA were reported elsewhere [20]. In summary, an electronic database search was performed in Medline/PubMed, EMBASE, and Cochrane Library from inception until November 30, 2021, without language restrictions.…”

“…The title or abstract and full text articles that met the prede ned inclusion criteria (see Additional File 2) were independently screened and extracted by four review authors (NB, JP, SP, CC). A total of 44 articles were included in the network meta-analysis, which was grouped by the outcome of interest measured at 6 and 12 months as follows: 1) The proportion of clinical remission or DAS28-ESR < 2.6 (transition from high disease activity or DAS28-ESR > 5.1 to remission, 'High to Remission') included 41 for 6 months and 18 studies for 12 months; 2) The proportion of transition from clinical high disease activity to low/moderate disease activity (DAS28-ESR > 2.6 to 5.1, 'High to Low/Moderate') included 9 for 6 months and 10 studies for 12 months; and 3) The proportion of patients who had serious infection included 33 studies [20]. Serious infection was selected to represent serious adverse event based on suggestions from medical experts.…”