The phase 2b/3 ALLEGRO (NCT03732807) trial investigated the efficacy of the JAK3/TEC inhibitor ritlecitinib in patients with alopecia areata (AA). All participants were aged ≥12 years of age with a ≥50% loss of scalp hair. The double-blind, randomised, controlled trial included 718 patients who were treated in various dose regimens of ritlecitinib or placebo over 24 weeks. Dosages ranged from 10 mg over 24 weeks to 200 mg as a loading dose for the initial 4 weeks followed by 50 mg daily (200/50 group).
An extension period of another 24 weeks followed with treatment continuation in the active drug groups and a switch to ritlecitinib for the placebo group participants. The primary endpoint was the rate of patients reaching a SALT score of ≤20. Among the secondary endpoints were achievement of SALT ≤10 and the proportion of participants who moderately or greatly improved in the PGI-C.
The mean age of the participants was 34 years with 13.8% to 15.2% aged 12 to 17 years in the study arms. Between 54.6% and 68.3% of enrolled participants were women. “The alopecia totalis (AT) and alopecia universalis (AU) group were defined by a SALT score of 100 and in the case of AU no eyebrows and no eyelashes, and this group comprised approximately 45% of participants across treatment arms; the mean baseline SALT score in the non-AT/AU group was about 78-87, and the mean duration of current AA episode was 3-4 years,” Prof. Brett King (Yale University School of Medicine, CT, USA) commented on baseline characteristics.
The response rates for the primary endpoint at week 24 were statistically significant versus placebo (2%) for the 200/50 mg (31%), 200/30 mg (22%), 50 mg (23%), and 30 mg (14%) dosing regimens with a P<0.001 for all comparisons. SALT ≤10 was achieved by 22%, 13%, 14%, and 11% of the same ritlecitinib dosing groups, respectively (P≤0.002 for all comparisons). Treatment responses continued to rise for both SALT≤20 and SALT≤10 until week 48. As for PGI-C, the proportion of patients that were ‘moderately’ or ‘greatly improved’ ranged from 42% to 53% in the same groups (P<0.001 vs placebo).
The participants experienced adverse events at a rate of 71% on placebo and 69.4% to 75.4% in the ritlecitinib arms. Most common were headache, nasopharyngitis, and upper respiratory infections, mostly mild to moderate. Severe adverse events occurred in 10 patients until week 24 and 14 patients up to week 48.
“In conclusion, ritlecitinib doses of 50 mg and 30 mg once daily with or without loading doses of 200 mg over 4 weeks were efficacious and generally well-tolerated over 48 weeks in patients with alopecia areata,” concluded Prof. King.