The relative efficacy of monotherapy with Janus kinase inhibitors, dupilumab and apremilast in adults with alopecia areata: Network meta-analyses of clinical trials.

Background: Janus kinase (JAK) inhibitors, biologics, and phosphodiesterase-4 (PDE-4) inhibitors are recent therapies for alopecia areata (AA)-albeit, knowledge gaps exist for these agents' relative efficacy.

Objectives: We determined the relative efficacy and safety of monotherapy with the aforementioned agents in adults with AA.

Methods: The literature was systematically searched; we used data from randomized trials that investigated the agents' efficacy-as per Severity of Alopecia Tool (SALT) scores. Bayesian network meta-analyses were used to determine relative efficacy and safety. Effect modification was determined using a generalized linear model on aggregate data; evidence quality was evaluated.

Results: Based on the surface under the cumulative ranking curve estimates obtained from multiple efficacy endpoints, regimens with the highest likelihood of achieving percent reduction in SALT scores, as well as a minimum 90%, 75% or 50% reduction in SALT scores are (in alphabetical order) baricitinib 4 mg once daily (QD), brepocitinib 60/30 mg QD, deuruxolitinib (CTP-543) 12 mg twice daily (BID), ritlecitinib 200/50 mg QD, ruxolitinib 20 mg BID and tofacitinib 5 mg BID. In contrast, dupilumab subcutaneous injections administered weekly and apremilast 30 mg BID were less likely to be effective. Discontinuation due to any adverse event was the least likely with oral JAK inhibitors, and more likely with dupilumab and apremilast.

Conclusions: Our results support the conduct of high-quality comparative trials to determine whether JAK inhibitors are more effective and safer than PDE4 inhibitors.