Janus Kinase Inhibitors for Alopecia Areata: A Systematic Review and Meta-Analysis of Randomized Clinical Trials

Background: Alopecia areata (AA) is a common chronic tissue-specific autoimmune disease, and several studies reported promising outcomes of Janus kinase (JAK) inhibitors for AA. This systematic review aimed to evaluate the efficacy and safety of JAK inhibitors for AA. Methods: We searched MEDLINE, EMBASE, and the Cochrane Controlled Register of Trials (CENTRAL) from inception until August 2022. All randomized clinical trials were included, and pairs of reviewers independently and in duplicate extracted data. We analyzed outcomes according to the intention-to-treat principle, and used DerSimonian-Laird random effects models by R version 3.6.3 (RStudio, Boston, MA). We evaluated the certainty of evidence using the GRADE (Grading of Recommendations Assessment, Development and Evaluation) approach. Results: Seven trials with 1710 patients proved eligible. JAK inhibitors lowered more Severity of alopecia tool (SALT) scores from the baseline of SALT scores compared to placebo (mean differences = - 33.69, 95% confidence intervals (CIs): -38.01 to -29.36, I2 = 96%), enable more participants to achieve 50% and 90% improvement in SALT scores from baseline compared to placebo (odds ratios (OR) = 5.23, 95%CIs: 1.41 to 19.23; OR = 8.78, 95%CIs: 4.30 to 17.94). JAK inhibitors enable more percentage of patients to achieve SALT score ≤10/20 over treatment period (OR = 9.39, 95%CIs: 3.97 to 22.19; OR = 7.39, 95%CIs: 4.82 to 11.33). JAK inhibitors may not cause more the treatment-related adverse events (relative risks (RR) = 1.10, 95%CIs: 1.00 to 1.21, I2 = 0%), severe adverse events (RR = 0.76, 95%CIs: 0.36 to 1.58) and discontinuation due to adverse event (RR = 0.85, 95%CIs: 0.43 to 1.68) compared with placebo. Conclusion: Oral and external JAK inhibitors resulted in more hair re-growth, the effect of oral JAK inhibitors was particularly pronounced, and all were well tolerated.Funding: None to declare. Declaration of Interest: All authors declare that they have no relevant conflicts of interest.