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Oral Janus kinase inhibitors such as brepocitinib, baricitinib, deuruxolitinib, and ritlecitinib are effective for the treatment of alopecia areata, causing significant regrowth of hair with only mild to moderate adverse effects.

Alopecia areata is characterized by the immune-mediated loss of hair in non-cicatricial patches. While this condition is self-limited, it is associated with substantial psychological impact given the long duration of hair regrowth. This literature review discusses the Janus kinase/signal transducer and activator of transcription (JAK/STAT) pathway and the role of Janus kinase inhibitors in managing alopecia areata. 

The study concluded that oral JAK inhibitors constitute a novel group of agents that promote significant hair regrowth while causing only mild to moderate adverse effects. These findings were published in the Indian Dermatology Online Journal.

Role of JAK Inhibitors in Alopecia Areata

Studies have demonstrated that the role of JAK inhibitors in managing alopecia areata is supported by the effects of these drugs on type I cellular immunity and IL-12- and IL-23-mediated T-cell responses. The JAK inhibitors are divided into first- and second- generation categories. The first-generation drugs (baricitinib and tofacitinib) are non-selective JAK inhibitors, whereas the second-generation drugs (filgotinib and upadacitinib) are selective JAK inhibitors.

Safety and Efficacy of JAK Inhibitors in Alopecia Areata

Tofacitinib is an effective JAK inhibitor, promoting ≥ 90% regrowth of hair in alopecia areata; however, a few studies report the inefficacy of the treatment and disease relapse in patients. The side effects of tofacitinib are transient and mild to moderate in intensity. The black box warning, however, indicates the risk for major adverse cardiovascular events, thrombosis, serious infections, and malignancy. While ruxolitinib has a similar boxed warning, no severe adverse effects have been reported in the medical literature, and the drug is known to cause up to 95% hair regrowth. Deuruxolitinib is a selective JAK1 and JAK2 inhibitor with a safety profile similar to other JAK inhibitors and a significant therapeutic response rate. Baricitinib is another JAK inhibitor with beneficial effects in patients with alopecia areata and black box warnings, including thrombosis, serious infections, and malignancy. Brepocitinib and ritlecitinib are novel JAK inhibitors that have been found to significantly decrease inflammatory markers, as demonstrated in scalp biopsy samples in a 2022 study by Guttman-Yassky et al.  

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Nonresponsiveness and Relapses With JAK Inhibitors

The persistence of CD8+ T cells and resident memory T cells contributes to the relapse of alopecia areata patients despite successful treatment with tofacitinib and ruxolitinib.

Oral JAK inhibitors such as brepocitinib, baricitinib, deuruxolitinib, and ritlecitinib are effective in the treatment of alopecia areata, leading to significant regrowth of hair with an improved side effect profile. However, further development of more targeted drugs is needed so as to minimize the associated adverse effects while maintaining efficacy.

Source:

Sardana, K., Bathula, S., & Khurana, A. (2023). Which is the ideal JAK inhibitor for alopecia areata – Baricitinib, tofacitinib, ritlecitinib or ifidancitinib – Revisiting the immunomechanisms of the JAK pathway. Indian Dermatology Online Journal, 14(4), 465–474. https://doi.org/10.4103/idoj.idoj_452_22