JAK Inhibitor Combo Shows Promise in Alopecia Areata

December 3, 2021

Ritlecitinib and brepocitinib showed significant improvement in scalp alopecia areata biomarkers.

Ritlecitinib and brepocitinib show significant improvement in scalp alopecia areata biomarkers, according to a phase 2a clinical trial published inthe Journal of Allergy and Clinical Immunology.

Researchers led by Emma Guttman-Yassky, MD, PhD, the Waldman Professor and System Chair of Dermatology at the Icahn School of Medicine at Mount Sinai in New York City, conducted a biopsy sub-study during the randomized, double-blind, placebo-controlled first 24 weeks of a phase 2a clinical trial that evaluated the efficacy and safety of ritlecitinib, an inhibitor of JAK3 and the tyrosine kinase expressed in hepatocellular carcinoma (TEC) kinase family, and brepocitinib, an inhibitor of tyrosine kinase 2 (TYK2)/JAK1 in the treatment of alopecia areata. 

They noted significant downregulation of Th1 and Th2 immune markers and increases in hair keratins with both treatments, and biomarkers were significantly associated to clinical improvement. Ritlecitinib showed high correlations between changes in Type 2 biomarkers and clinical improvement, the study showed.

These are the first biopsy results from a phase 2a randomized, double-blind, clinical trial that evaluated the JAK3/TEC inhibitor ritlecitinib and the TYK2/JAK1 inhibitor brepocitinib in patients with alopecia areata, Dr. Guttman says. There was much higher and more significant changes in patients with a shorter duration of time since the last hair regrowth, supporting the need for early intervention in alopecia areata.

“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,” says Dr. Guttman in a news release.  “The biomarker data is robust, even at an early timepoint 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.“

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