Alopecia areata: encouraging response rates with JAK3/TEC inhibition

Ritlecitinib at various dosages led to improvements in the Severity of Alopecia Tool (SALT) scores of patients with alopecia areata (AA) in the phase 2b/3 ALLEGRO trial. Over 48 weeks, the Janus kinase (JAK)3/TEC inhibitor was well tolerated.

The JAK3/TEC inhibitor ritlecitinib was assessed as a therapy for AA in the phase 2b/3 ALLEGRO (NCT03732807) trial, after recently demonstrating efficacy in a phase 2a study [1,2]. The enrolled participants were aged ≥12 years and had a ≥50% loss of scalp hair [1]. The double-blind, randomised-controlled trial included 718 patients who were treated in various dose regimens of ritlecitinib or placebo over 24 weeks. The 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). This was followed by an extension period of another 24 weeks 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 ≤20. Secondary endpoints included achievement of SALT ≤10 and the proportion of participants who moderately or greatly improved their Patient Global Impression of Clinical Status (PGI-C) score.

The mean age of the participants was 34 years with 13.8% to 15.2% aged 12 to 17 years in the study arms. “The alopecia totalis and alopecia universalis groups were defined by a SALT score of 100 and, in the case of alopecia universalis, no eyebrows and no eyelashes, and this group comprised approximately 45% of participants across treatment arms,” Prof. Brett King (Yale University School of Medicine, CT, USA) commented on the baseline characteristics.

At week 24, the response rates for the primary endpoint were statistically significant for the 200/50 mg (31%), 200/30 mg (22%), 50 mg (23%), and 30 mg (14%) dosing regimens versus placebo (2%) 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 69.4–75.4% in the ritlecitinib arms. Most common were headaches, 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 AA,” concluded Prof. King.

1. 
   
   1. King B. Efficacy and safety of ritlecitinib (PF-06651600) in patients with alopecia areata and ≥50% scalp hair loss: results from the international ALLEGRO phase 2b/3 randomized, double-blind, placebo-controlled study (NCT03732807). D3T01.1C, EADV Congress 2021, 29 Sept–2 Oct.
   2. King B, et al. J Am Acad Dermatol. 2021;85(2):379–387.

 

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Posted on 18 November, 202128 March, 2024