Janus kinase inhibitors ritlecitinib and brepocitinib improve scalp alopecia biomarkers

Published: December 1, 2021

Alopecia areata (AA) is an autoimmune disorder that involves hair loss that can range from partial to complete loss of scalp hair, through to total body hair loss. Currently, no Food and Drug Administration-approved treatments exist for patients with moderate-to-severe AA, and available therapies are either ineffective, inconvenient for patients, or unsuitable for long-term use. Clinical testing of the janus kinase (JAK) inhibitors ritlecitinib and brepocitinib has shown successful hair regrowth in many patients with AA in a phase 2a randomized, placebo-controlled, double-blind, clinical trial.

In a recent article published in The Journal of Allergy and Clinical Immunology (JACI), Guttman-Yassky et al. report findings from the analysis of scalp biopsies from a subset of patients who took part in the phase 2a clinical trial. Lesional scalp (completely void of hair) and nonlesional scalp biopsies (taken from the center of an area with normal hair density, at least 1 cm away from lesions) were obtained before treatment (week 0) and at weeks 12 and 24. Biopsies were analyzed for gene expression and cellular changes, including for immune, hair keratins and keratin-associated related markers, and changes in these markers were also correlated with extent of hair regrowth.

For both ritlecitinib and brepocitinib, hair regrowth was associated with a decreased expression in immune markers and increased hair keratins and keratin-associated proteins at 12 and 24 weeks of treatment initiation. Patients with AA who had shorter duration (<3.5 years) of active hair regrowth had larger modulation in molecular and cellular markers, which were correlated with greater hair regrowth, with a lesser magnitude of changes in patients with longer duration since the last episode of hair regrowth. Hair regrowth with Ritlecitinib and Brepocitinib were significantly correlated with decreases in immune biomarkers, including some Th2 and Th1 markers (i.e IL-13, IFNG), and increases in hair associated keratins.

These findings provide further support that treatment with ritlecitinib or brepocitinib is beneficial in the management of patients with AA, and provide insights into the pathogenesis of AA.

The Journal of Allergy and Clinical Immunology (JACI) is an official scientific journal of the AAAAI, and is the most-cited journal in the field of allergy and clinical immunology.

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