NEW YORK (Reuters Health) – Treatment with the investigational oral Janus kinase (JAK) inhibitors ritlecitinib or brepocitinib led to molecular and clinical improvement in scalp lesions in patients with alopecia areata enrolled in a biopsy sub-study of the phase-2 ALLEGRO trial.
“Alopecia areata is a chronic, relapsing autoimmune disorder with an approximate 2% lifetime incidence among patients in the United States, affecting both adult and pediatric populations,” the study team notes in the Journal of Allergy and Clinical Immunology.
There currently is no U.S. Food and Drug Administration (FDA)-approved treatment for patients with moderate-to-severe alopecia areata. Available treatment options, including intra-lesional steroid injections, contact sensitization, and systemic immunosuppressants, “show limited efficacy, are inconvenient for patients, and/or are unsuitable for long-term use,” they point out.
JAK inhibitors have shown encouraging results in the treatment of alopecia areata. Ritlecitinib is an oral inhibitor of JAK3 and the tyrosine kinase expressed in hepatocellular carcinoma (TEC) kinase family, and brepocitinib is an oral inhibitor of tyrosine kinase 2 (TYK2)/JAK1. Both are from Pfizer, which funded the study.
The primary efficacy endpoint of the ALLEGRO trial was change from baseline in the Severity of Alopecia Tool (SALT) score at 24 weeks. Patients could elect to participate in the optional biopsy sub-study that took place during the randomized, double-blind initial 24 weeks of the trial.
The average change (improvement) in the SALT score from baseline to 24 weeks was 24.9 for the ritlecitinib group and 38.8 for the brepocitinib group versus 7.6 for the placebo group.
In the biopsy sub-study, which included 46 of the original 142 patients, researchers observed significant downregulation of Th1 and Th2 immune markers and increases in hair keratins and keratin-associated proteins with both JAK inhibitors and these biomarker changes were significantly associated to clinical improvement.
“The results are exciting as it associates hair regrowth with changes in type 2 and type 1 immune cytokines, as well as increases in hair keratins with hair regrowth,” study investigator Dr. Emma Guttman-Yassky of Icahn School of Medicine at Mount Sinai, in New York, told Reuters Health by email.
“The biomarker data is robust, even at an early time point of 12 weeks, which is even before significant hair regrowth occurs. This suggests that scalp biomarkers may predict early clinical responses of hair regrowth in alopecia,” said Dr. Guttman-Yassky.
SOURCE: https://bit.ly/31tNTVW Journal of Allergy and Clinical Immunology, online December 1, 2021.