JAK3/TEC blockade leads to long-term improvement in alopecia areata

Ritlecitinib sustained efficacy in treatment up to month 36 without new safety signals. Patient-reported outcomes improved already after 3 months.

Median range of exposure was about 17 months

Ritlecitinib is a selective inhibitor of JAK3 and the TEC kinase that previously showed efficacy in AA in the phase 2b/3 ALLEGRO study (NCT03732807)1. At this year´s EADV meeting, Dr Athanasios Tsianakas (Fachklinik Bad Bentheim, Germany) reported interim results from the de novo arm of ALLEGRO-LT (NCT04006457), an ongoing phase 3 study investigating the long-term safety and efficacy of ritlecitinib in patients with AA2. 

Included in the ALLEGRO-LT study were either roll-over participants from previous trials or de novo participants. De-novo participants were first treated with 200 mg ritlecitinib, once daily, for 4 weeks (induction dose) followed by the maintenance dose of 50 mg. Key inclusion criteria of de novo participants were an age of ≥12 years and a diagnosis of AA with an ≥25% scalp hair loss due to AA. Dr Tsianakas presented the results of the de-novo arm up to month 36. 

The median range of exposure was about 17 months. “All in all, 85% of the included participants were taking the drug for more than 12 months,” Prof Tsianakas said. At data cut-off, 21.6% of participants had discontinued, but only 3% due to adverse events. 

1,448 adverse events recorded from 447 participants

Regarding efficacy, the proportion of participants showing a maximum of 20% hair loss in the Severity Alopecia Tool (SALT) score, a global severity score, was evaluated up to month 24. “We can see that the curve nicely goes upwards until a year and stays steady at about 70%,” Prof Tsianakas elucidated. The more stringent SALT 10 results level out at about 56% after a year. The high efficacy seen in ALLEGRO-LT is mirrored in the positive participant reported outcome, the proportion of participants who moderately or greatly improved their Patient Global Impression of Clinical Status (PGI-C) score. Already after 5 months, 57% of participants felt their hair growth had moderately or greatly improved, this percentage went up to about 78% at month 24. 

Among the 447 participants included in the safety analysis, a total of 1,448 adverse events were recorded. From the de-novo group, 78% developed adverse events, but 94.6% were mild to moderate in severity. The most frequent side effects were headache, SARS-CoV-2 test positive, and acne. Importantly, no opportunistic infections and no clinically relevant median changes from baseline in haematological parameters were observed. 

Taken together, these long-term data are consistent with the primary ALLEGRO study results.

References
  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 - Virtual, 29 September – 2 October.
  2. Tsianakas A. Long-term safety and efficacy of ritlecitinib in adults and adolescents with alopecia areata: interim results from the ALLEGRO-LT phase 3, open-label trial. D3T01.1G, EADV Congress 2022, Milan, Italy, 7–10 September.