Rapid Therapeutic Effect in Alopecia Areata Seen With JAK3, TYK2, and JAK1 Inhibitors

A man with alopecia
A man with alopecia
PF-06700841 and PF-06651600 were found to have an effect onset of 6 and 4 weeks, respectively in patients with moderate to severe alopecia areata.

The following article is part of conference coverage from the 2019 American Academy of Dermatology Annual Meeting in Washington, DC. Dermatology Advisor’s staff will be reporting breaking news associated with research conducted by leading experts in dermatology. Check back for the latest news from AAD 2019.

PF-06700841, a janus kinase 3 (JAK3) inhibitor, and PF-06651600, an inhibitor of tyrosine kinase 2 (TYK2) and JAK1, were found to have an effect onset of 4 and 6 weeks, respectively, in patients with moderate to severe alopecia areata, according to the results of a phase 2a trial presented at the American Academy of Dermatology 2019 Annual Meeting, held March 1 to 5 in Washington, DC.

For this randomized, double-blind, multicenter study (ClinicalTrials.gov identifier: NCT02974868), a total of 142 patients (aged 18-75 years) with moderate to severe alopecia areata were enrolled. Study participants underwent a 4-week-long induction period, followed by a maintenance treatment period (lasting an additional 20 weeks). During the induction phase of the treatment, patients were randomly assigned to receive PF-06651600 (200 mg daily; n=48), PF-06700841 (60 mg daily; n=47), or placebo (n=47). Maintenance doses were 50 mg daily for PF-06651600 and 30 mg daily for PF-06700841.

A significant difference in Severity of Alopecia Tool (SALT) score from baseline with drug treatment vs placebo indicated onset of drug effect. The effect of disease duration (ie, <3.5 vs ≥3.5 years’ duration of current alopecia areata episode) on treatment efficacy for both drugs was also examined using SALT score changes from baseline during the 24-week study period.

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SALT scores at baseline were comparable between groups (PF-06651600, 89.4±15.8; PF-06700841, 86.4±18.1; placebo, 88.4±18.1). Clinically evident therapeutic effects were observed for PF-06700841, starting at 4 weeks of treatment (mean difference in SALT score compared with placebo, 7.7; P =.002), and at 6 weeks of treatment for PF-06651600 (mean difference in SALT score compared with placebo, 12.6; P =.002). After 24 weeks of treatment with either drug, responders recovered a full head of hair.

Study participants with duration of current alopecia episode <3.5 vs ≥3.5 years experienced faster onset of drug effect for PF-06700841 (4 weeks, n=33 [P <.001] vs 8 weeks, n=14 [P <.001], respectively), and similar onset with PF-06651600 (6 weeks; P <.05 for both).

The effects of the study drugs were more visible in patients with long vs short duration of current alopecia episode.

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Reference

Peeva E, Banerjee A, Guttman-Yassky E, et al. Oral janus kinase inhibitors PF-06700841 and PF-06651600 provide clinically evident therapeutic effect at 4 and 6 weeks in patients with alopecia areata and greater efficacy over 24 weeks in patients with a shorter duration of their current alopecia episode: Results of a randomized phase 2a trial. Presented at: American Academy of Dermatology 2019 Annual Meeting; March 1-5, 2019; Washington, DC.