Efficacy and safety of jakinibs in rheumatoid arthritis: a systematic review and meta-analysis

Abstract

Objectives To assess the e cacy and safety of jakinibs for the treatment of active rheumatoid arthritis (RA) in patients with an inadequate response or intolerance to conventional synthetic or biologic disease-modifying antirheumatic drugs (DMARDs). Methods A systematic search was conducted in PubMed, Embase and the Cochrane Library. Randomized placebo-controlled trials (RCTs) of jakinibs in RA patients were eligible. The effective outcome was RA improvement to reach an American College of Rheumatology 20%/50%/70% (ACR20/50/70) response rate at week 12 and 24 after treatment. The safety outcomes included treatment-emergent adverse events (TEAEs), serious adverse events (SAEs), discontinuations due to adverse events, infections and serious infections. Results Twenty-eight randomized, double-blind, controlled trials including 14500 patients were included. Both at week 12 and 24, the pooled analysis was suggestive of an effective treatment with jakinibs, represented as the increased clinical response of ACR20, ACR50 and ACR70. The subgroup analysis based on different types of jakinibs demonstrated that only pe citinib treatment had no impact on the clinical response of ACR50 or ACR70 at week 12. Jakinibs were associated with an increased incidence of infections at week 12 and TEAEs and infections at week 24. No increase in the risk of SAEs, discontinuations due to adverse events, or serious infections was observed in comparisons between treatment with jakinibs and treatment with placebo in these patients. Conclusions Jakinibs are e cacious and well tolerated in RA patients up to a period of 24 weeks, although they are associated with an increased risk of infectious complications. MethodsThis systematic review and meta-analysis adhered to the recommendations of the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines for the meta-analysis of interventional studies [17]. The authors declare that all supporting data are available within the article and/or supplementary materials. This study did not require ethical approval or informed consent since all analyses were based on previously published data. Data sources and search strategyWe performed an exhaustive search for studies that evaluated the e cacy and safety of jakinibs in patients with active RA in bibliographic databases, including PubMed, EMBASE and the Cochrane Library, from their inceptions to February 1, 2020. The papers were not restricted concerning publication status or language. A combination of the following keywords was used: "rheumatoid arthritis", "ra", and "protein kinases inhibitor" "janus kinase inhibitor", "jak inhibitor", and "jakinib". The search was independently performed by two investigators (YY and ML), and discrepancies in the study selection were resolved by consensus. The search strategy is listed in online supplementary table S1. The references in the enrolled trials or metaanalyses were also screened manually to nd relevant original studies. Study selectionThe relevant data from the RCTs comparing the...