Efficacy and safety of ritlecitinib, an oral JAK3/TEC family kinase inhibitor, in adolescent and adult patients with alopecia totalis and alopecia universalis

Abstract

This post-hoc analysis of the ALLEGRO phase 2b/3 study (NCT03732807) evaluated the efficacy and safety of ritlecitinib, an oral Janus kinase 3/TEC family kinase inhibitor, in patients with alopecia totalis (AT) and alopecia universalis (AU). Patients aged ≥ 12 years with alopecia areata (AA) and ≥50% scalp hair loss received once-daily ritlecitinib 50 or 30 mg (± 4-week 200-mg loading dose) or placebo for 24 weeks. In a subsequent 24-week extension period, the ritlecitinib groups continued their doses and patients initially assigned to placebo switched to ritlecitinib (200/50 or 50 mg daily). In this analysis, clinician- and patient-reported hair regrowth outcomes were assessed at weeks 24 and 48 in four AA subgroups: AT/AU, AT, AU, and non-AT/AU. Safety was monitored throughout. Of the 718 randomized patients, 151 (21%) and 147 (20%) were defined as having AT or AU, respectively. At week 24, Severity of Alopecia Tool (SALT) score ≤20 (≤20% scalp hair loss) response rates were higher in the ritlecitinib-treated AT/AU, AT, and AU groups (7%-14%, 7%-21%, and 4%-10%, respectively) vs the placebo group (0% in the AT/AU, AT, and AU groups). The proportions of patients with a SALT score of ≤20 increased through week 48 (AT/AU, 13%-31%; AT, 11%-27%; AU, 6%-41%). Additionally, at week 24, 25%-43%, 32%-42%, and 12%-50% of patients with AT/AU, AT, and AU, respectively, who received ritlecitinib achieved a moderately or greatly improved response based on the Patient Global Impression of Change scale. Response rates generally increased through week 48 and were similar across AA subgroups. In patients with AT/AU, ritlecitinib was well tolerated with a safety profile consistent with that of the overall AA population. Ritlecitinib demonstrated clinical efficacy, patient-reported improvement, and an acceptable safety profile in patients with AT and AU through week 48. A plain language summary of this study is available at https://doi.org/10.25454/pfizer.figshare.26879161. Clinicaltrials.gov: NCT03732807.

Keywords: ALLEGRO; JAK3/TEC; alopecia areata; alopecia totalis; alopecia universalis; hair loss; kinase inhibitor; ritlectinib.