Efficacy and safety of the oral Janus kinase 3/tyrosine kinase expressed in hepatocellular carcinoma family kinase inhibitor ritlecitinib over 24 months: integrated analysis of the ALLEGRO phase IIb/III and long-term phase III clinical studies in alopecia areata.

Background: The ALLEGRO phase IIa and IIb/III (NCT02974868 and NCT03732807) studies have demonstrated that ritlecitinib is effective and well tolerated in adults and adolescents with alopecia areata (AA) up to 48 weeks.

Objectives: To assess the efficacy of ritlecitinib through month 24 and safety through data cutoff in the ALLEGRO phase IIb/III study and the ongoing long-term open-label phase III ALLEGRO-LT study (NCT04006457).

Methods: Patients aged ≥ 12 years with AA and ≥ 50% scalp hair loss from ALLEGRO IIb/III who rolled over to ALLEGRO-LT after up to 48 weeks were included. Proportions of patients with responses based on clinician-reported Severity of Alopecia Tool (SALT) scores of ≤ 20 and ≤ 10, eyebrow assessment (EBA) and eyelash assessment (ELA), patient global impression of change (PGI-C) and patient satisfaction with hair growth were reported through month 24 for patients who received ritlecitinib 50 mg daily with or without a 200-mg 4-week daily loading dose. Observed and imputed data [last observation carried forward (LOCF)] were reported up to 9 December 2022. Safety was assessed throughout.

Results: At month 12, a SALT score ≤ 20 was achieved by 45.1% and 45.9% (observed) and 40.3% and 41.8% (LOCF) of the 191 and 194 patients who received ritlecitinib 50 mg and ritlecitinib 200 mg/50 mg, respectively. At month 24, these proportions increased to 60.8% and 63.1% (observed) and 46.1% and 50.8% (LOCF), respectively. Patients with abnormal EBA or ELA scores at baseline achieved responses at month 24 [EBA observed: 57.6% (50 mg), 61.0% (200/50 mg); EBA LOCF: 46.8% (50 mg), 50.9% (200/50 mg); ELA observed: 51.2% (50 mg), 62.7% (200/50 mg); ELA LOCF: 43.2% (50 mg), 51.7% (200/50 mg)]. PGI-C response was achieved by patients at month 24 [observed: 70.0% (50 mg), 76.4% (200/50 mg); LOCF: 56.6% (50 mg), 65.5% (200/50 mg)]. Safety profiles for both treatment groups were consistent with the known safety profile of ritlecitinib.

Conclusions: Ritlecitinib has clinically meaningful and sustained efficacy beyond 1 year with a favourable safety and tolerability profile, supporting its long-term use in patients aged ≥ 12 years with AA.

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