Janus Kinase Inhibitors for Alopecia Areata: A Systematic Review and Meta-Analysis

IMPORTANCE: Alopecia areata (AA) is a common chronic tissue-specific autoimmune disease. Several studies have reported outcomes of Janus kinase (JAK) inhibitors for treating AA, but limited evidence has emerged. OBJECTIVE: To evaluate the effectiveness and safety associated with JAK inhibitors for AA. DATA SOURCES: MEDLINE, Embase, and CENTRAL (Cochrane Central Register of Controlled Trials) were searched from inception until August 2022. STUDY SELECTION: Only randomized clinical trials (RCTs) were included. Pairs of reviewers independently and in duplicate selected the studies. DATA EXTRACTION AND SYNTHESIS: Hartung-Knapp-Sidik-Jonkman random-effects models were used for meta-analysis. Certainty of evidence was evaluated using the Grading of Recommendations, Assessment, Development, and Evaluations (GRADE) approach. This study is reported according to the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) reporting guideline. MAIN OUTCOMES AND MEASURES: The primary outcomes of interest were (1) proportion of patients who achieved 30%, 50%, and 90% improvement in Severity of Alopecia Tool (SALT) score from baseline, (2) change from baseline SALT score, and (3) treatment-related adverse event (AE). RESULTS: Seven RCTs with 1710 patients (1083 females [63.3%]; mean [SD] age range, 36.3 [10.4] to 69.7 [16.2] years) were eligible and included in the study. JAK inhibitors were associated with more patients achieving 50% improvement (odds ratio [OR], 5.28 [95% CI, 1.69-16.46]; GRADE assessment: low certainty) and 90% improvement (OR, 8.15 [95% CI, 4.42-15.03]; GRADE assessment: low certainty) in SALT score from baseline compared with placebo. JAK inhibitors were associated with more lowered SALT scores from the baseline compared with placebo (mean difference [MD], –34.52 [95% CI, −37.80 to −31.24]; GRADE assessment: moderate certainty), and JAK inhibitors were not associated with more treatment-related AEs (relative risk [RR], 1.25 [95% CI, 1.00-1.57]; GRADE assessment: high certainty) compared with placebo. High certainty of evidence showed that JAK inhibitors may not be associated with more severe AEs compared with placebo (RR, 0.77; 95% CI, 0.41-1.43). The subgroup analysis showed that oral JAK inhibitors were more efficient than placebo (change from baseline SALT scores: MD, –36.80; 95% CI, −39.57 to −34.02), and no difference was found between external JAK inhibitors and placebo (change from baseline SALT scores: MD, –0.40; 95% CI, −11.30 to 10.50). CONCLUSIONS AND RELEVANCE: Results of this systematic review and meta-analysis suggest that JAK inhibitors, compared with placebo, were associated with hair regrowth and that the outcome of oral JAK inhibitors was better than the external route of administration. Although the safety and tolerability of JAK inhibitors were acceptable, longer RCTs are needed to further assess the effectiveness and safety of these treatments for AA.