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The treatment of AA with brepocitinib and ritlecitinib is associated with a reduction in the SALT scores. This is also related to the downregulation of TH1 cells and the upregulation of hair keratins. Future clinical trials are required to assess the safety, efficacy, dosage, and duration of treatment with JAK inhibitors.

Alopecia areata (AA) is an autoimmune disorder characterized by an unpredictable course of hair loss. Janus kinase (JAK) inhibitors have gained recognition in different studies for the treatment of AA. This phase 2a randomized placebo-controlled multicenter, double-blind clinical trial, published in The Journal of Allergy and Clinical Immunology, evaluated the safety and efficacy of ritlecitinib, an oral JAK3 inhibitor, and brepocitinib, an oral TYK2/JAK1 inhibitor. The research investigators conducted a biopsy study under this randomized controlled trial to assess the change in biomarkers in biopsy samples from scalp lesions. The investigators also evaluated the relationship between biomarkers and hair regrowth measured via the Severity of Alopecia Tool (SALT) score.
The study included 142 participants, who received brepocitinib (n=47), ritlecitinib (n=48), and placebo (n=47) with 1:1:1 randomization. At week 24 both ritlecitinib and brepocitinib had improved the lesional scalp transcriptome toward a non-lesional profile by greater than 100%. At week 12 of the study, greater improvement in the scalp was observed with brepocitinib, whereas, at week 24, greater improvements were observed with ritlecitinib. The JAK inhibitors lead to significant downregulation of TH1 cells and natural killer (NK)/T-cell activation. The JAK inhibitors were associated with the upregulation of keratin-associated proteins (KRTAPs) and hair keratins (KRTs). Clinical improvement with brepocitinib and ritlecitinib was related to a reduction in the SALT score. The patients with longer episodes of AA hair loss demonstrated minimal molecular change.
In summary, the biopsy sub-study of the RCT supported the efficacy of brepocitinib and ritlecitinib in the management of AA patients with ≥ 50% scalp hair loss. The changes in the molecular biomarkers of hair loss were observed during weeks 12 and 24. The investigators observed ritlecitinib to be more effective than brepocitinib for AA at week 24 of the study.
Reference
Guttman-Yassky, E., Pavel, A. B., Diaz, A., Zhang, N., Del Duca, E., Estrada, Y., . . . Peeva, E. (2022). Ritlecitinib and brepocitinib demonstrate significant improvement in scalp alopecia areata biomarkers. Journal of Allergy and Clinical Immunology, 149(4), 1318-1328. https://doi.org/10.1016/j.jaci.2021.10.036

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