#alopecia areata - research shows promising new biologic treatments.

Pharmacological inhibition of Janus kinase (JAK) family protein tyrosine kinases led to recovery of hair growth in three patients with alopecia areata (AA), according to New York-based researchers. The early clinical data are quite striking and promising, with near complete hair regrowth seen in the majority of patients. It will be exciting to pursue larger clinical trials with both oral and topical JAK inhibitors to see how we can best treat alopecia areata safely and effectively.

In a paper online August 17 in Nature Medicine, Dr. Clynes and Dr. Angela M. Christiano and colleagues at Columbia University note that this common autoimmune disease results from damage of the hair follicle by T cells. However, the immune pathways involved in autoreactive T cell activation have not been defined.

To do so, the team first studied a mouse strain that develops spontaneous AA similar to that in humans. Further investigation of mouse and patient cells revealed how the T cells are instructed to attack and identified several key immune pathways that could be targeted by JAK inhibitors.

Two FDA-approved JAK inhibitors, ruxolitinib and tofacitinib, tested separately by the researchers were able to block these immune pathways and stop the attack on the hair follicles. In mice with extensive hair loss from the disease, both drugs completely restored the animals' hair within 12 weeks. The effects were long-lasting, with new hair persisting for several months after stopping treatment.

Given these encouraging findings, the researchers tested JAK inhibition by treating three patients with moderate to severe disease orally with ruxolitinib, 200 mg twice daily. All three patients exhibited near-complete hair regrowth within three to five months of oral treatment. Comparison of biopsies obtained at baseline and after 12 weeks of treatment demonstrated reduced perifollicular T cell infiltration.

In dermatology, it is often desirable to have both oral and topical delivery methods for a given drug, such as corticosteroids, for different uses. Oral JAK inhibitors are being tested for a variety of inflammatory diseases, and are approved for rheumatoid arthritis. Topical and oral JAK inhibitors have already been tested for psoriasis.  The researchers also commented that there may be other skin conditions that will benefit from a topical JAK inhibitor, such as vitiligo and cutaneous lupus.