Oral Administration of JAK Inhibitors Shows Improved Response in Alopecia Areata

Oral administration of Janus kinase (JAK) inhibitors may provide better efficacy vs topical and sublingual formulations in the treatment of alopecia areata (AA), according to study findings published in Frontiers in Pharmacology.

Although several therapeutic approaches are available for the management of AA, including corticosteroids, minoxidil, and topical immunotherapy, responses to these treatments vary widely, the researchers noted, with adverse events occuring especially frequently in systemic medications.

In exploring more effective and less toxic drugs for AA, targeted therapies, including JAK inhibitors, are considered to be a preferable treatment option. But there remains a lack of comprehensive evidence based on prospective studies regarding the efficacy and safety of these drugs in AA.

“Clinical statistics regarding the efficacy and safety of JAK inhibitors are required to provide a better insight in this new treatment strategy,” wrote the study authors.

They conducted a systematic review and subsequent meta-analysis to evaluate the safety and efficacy of JAK inhibitors for AA. Additional subgroup analyses were conducted to determine the relative efficacy of JAK inhibitors in different administration route (oral vs topical vs sublingual administration) and to identify more factors influencing the good response to JAK inhibitors in patients with AA.

Clinical studies registered in the PubMed, EMBASE, and Cochrane library databases from inception to June 17, 2022 that evaluated the efficacy and safety of the JAK inhibitors tofacitinib, ruxolitinib, baricitinib, ritlecitinib, and brepocitinib were eligible for inclusion in the systematic review.

“The efficacy outcomes included good response (defined as 50% improvement in Severity of Alopecia Tool [SALT] scores), complete response (defined as 90% improvement in SALT scores), the percent change from baseline in SALT score, and recurrence. The safety outcomes included the incidence rates of adverse events,” noted the study authors.

After evaluation of potentially relevant reports, 14 studies (5 randomized controlled trials [RCTs] and 9 non-RCTs), enrolling a total of 1845 patients, were included for quantitative analysis. Non-RCTs included comparative efficacy data on the oral, topical, and sublingual administration of JAK inihibitors, and RCTs included data on only oral and topical formulations.

Specific to RCTs, oral JAK inhibitors exhibited a significantly higher good response rate (RR) compared with controls (RR, 6.86; 95% CI, 2.91-16.16), whereas topical JAK inhibitors did not show any difference compared with controls (RR, 1.00; 95% CI, 0.31–3.18).

The pooled rate of good response in the non-RCTs for oral, topical, and sublingual JAK inhibitors were 63% (95% CI: 44%–80%), 28% (95% CI: 1%–72%), and 11% (95% CI: 1%–29%), respectively, again showing the greater good response observed with oral formulations. No significant difference based on the route of administration was observed for complete response.

Regarding recurrence outcomes, the pooled recurrence rate in patients treated with JAK inhibitors was 54% (95% CI: 39%–69%), mainly due to the withdrawal of JAK inhibitors. No difference was observed in the risk of experiencing adverse events in the RCTs, with reported adverse events with high incidence rate in the non-RCTs indicated to be mostly mild and manageable.

Researchers noted that one of the major limitations of the review was the high heterogeneity of the studies, which could result from the inclusion of 3 routes of administration.

“For this reason, a random effects model was used and subgroup analyses were conducted to reduce heterogeneity,” they added.

They concluded that the high recurrence rate after withdrawal of JAK inhibitors warrants consideration for continuous treatment to maintain efficacy.

Reference

Yan D, Fan H, Chen M, et al. The efficacy and safety of JAK inhibitors for alopecia areata: A systematic review and meta-analysis of prospective studies. Front Pharmacol. 2022;13:950450. doi:10.3389/fphar.2022.950450