Efficacy and Safety of Janus Kinase Inhibitors in Polymyalgia Rheumatica: A Systematic Review

Polymyalgia rheumatica (PMR) is a common inflammatory disease of older adults; glucocorticoids remain the mainstay of treatment despite substantial cumulative toxicity. Janus kinase (JAK) inhibitors block cytokine signalling implicated in PMR, but their role has not been systematically appraised. We conducted a systematic review, prospectively registered on the International Prospective Register of Systematic Reviews (PROSPERO; CRD420261364002) and reported according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) 2020 statement and the Synthesis Without Meta-analysis (SWiM) guideline. Embase, Medical Literature Analysis and Retrieval System Online (MEDLINE), the Cochrane Library, and PubMed were searched from inception to 18 May 2026 without language or date restrictions. Eligible studies reported original efficacy or safety data for a JAK inhibitor in adults with PMR diagnosed using an established framework. Risk of bias was assessed with design-matched tools, findings were synthesised narratively by clinical comparison, and certainty was rated with the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach separately for each comparison. Four studies (154 participants randomised or enrolled, 86 receiving a JAK inhibitor) contributed to the primary synthesis, and a mixed PMR and giant cell arteritis (GCA) case series was retained as context. In the only double-blind placebo-controlled trial, baricitinib increased the proportion of patients achieving low disease activity without oral glucocorticoids at week 12 (77.8% vs 13.3%; relative risk (RR) 5.8, 95% confidence interval (CI) 3.2-10.6). An open-label trial reported tofacitinib to be non-inferior to prednisone in a complete analysis in which every participant in both arms responded; on recalculation, this conclusion held only at the margin boundary and was not robust to missing data. A retrospective cohort and a single-arm study suggested glucocorticoid sparing but could not separate a drug effect from confounding or concurrent tapering. Certainty was low for the randomised comparisons and very low otherwise, and safety data were too sparse to characterise uncommon harms. Baricitinib may increase glucocorticoid-free low disease activity in recent-onset PMR (low certainty), and evidence for tofacitinib is of low to very low certainty. These preliminary findings do not establish efficacy for JAK inhibitors as a class, support routine use, or identify a preferred patient population; adequately powered, blinded trials are needed.