Comparative Efficacy and Safety of Peficitinib Versus Tofacitinib and Baricitinib for Treatment of Rheumatoid Arthritis: A Systematic Review and Network Meta-Analysis.

Introduction: Peficitinib, a Janus kinase (JAK) inhibitor, is approved for clinical use in Japan, Korea, and Taiwan, but head-to-head comparisons versus other JAK inhibitors are lacking. We indirectly compared peficitinib, tofacitinib, and baricitinib for rheumatoid arthritis treatment.

Methods: We searched MEDLINE, Embase, the Cochrane Central Register of Controlled Trials, ClinicalTrials.gov, and congress archives up until February 12, 2019, for randomized controlled trials of peficitinib, tofacitinib, and baricitinib. Efficacy (American College of Rheumatology responses, disease activity scores, modified total Sharp score, Simplified Disease Activity Index [SDAI]) and safety outcomes were compared using a Bayesian network meta-analysis. The Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) consensus was followed for reporting results. A network meta-regression assessed the impact on outcomes of proportions of patients receiving concomitant methotrexate or of Asian ethnicity.

Results: The network meta-analysis included 21 randomized controlled trials. At 12 weeks, all evaluable efficacy outcomes were comparable or improved with peficitinib 150 mg and 100 mg once daily, versus baricitinib 2 and 4 mg once daily and tofacitinib 5 mg twice daily. At 24 weeks, efficacy outcomes were comparable or improved for each peficitinib dose versus baricitinib and tofacitinib. Risk of adverse events and serious adverse events at 12 weeks were similar with peficitinib 100 and 150 mg versus baricitinib and tofacitinib. The proportion of patients receiving concomitant methotrexate had no effect on any outcome analyzed, but Asian ethnicity had a positive effect on multiple efficacy outcomes.

Conclusions: Peficitinib had comparable efficacy versus tofacitinib and baricitinib for reduction in disease activity as measured by SDAI, and for reduction in progression of joint damage as measured radiographically. No notable differences in safety outcomes were observed. Further studies are required to better characterize the impact of ethnicity on the efficacy of JAK inhibitors.