Drug Causes Significant Hair Growth in Alopecia Patients

The FDA-approved Janus kinase (JAK) inhibitor ruxolitinib, typically used to treat bone marrow malignancies, caused an average hair regrowth of 92% in individuals who suffered from alopecia areata.

Prior research conducted by the study authors identified the specific immune cells, and the dominant inflammatory signaling pathways responsible for attacking the hair follicle in alopecia areata, putting them into a dormant state.

After conducting subsequent experiments with mice and human hair follicles, researchers demonstrated that topical and oral JAK inhibitors could reawaken dormant follicles by blocking inflammatory signaling. Two of these FDA inhibitors include ruxolitinib, for bone marrow malignancies, and tofacitinib, for rheumatoid arthritis.

“These disorders are both characterized by dysregulated signaling pathways, similar to alopecia areata, which is dominated by the interferon signaling pathway,” said researcher Raphael Clynes, MD, PhD. “Even though the diseases are very different, this common feature gave us the initial idea to test JAK inhibitors in people with alopecia.”

The study’s findings were published in the Journal of Clinical Investigation/Insight.

Researchers wanted to test their hypothesis by conducting a small, open-label clinical trial that involved 12 patients with moderate-to-see alopecia areata, and who had more than 30% of hair loss.

During the trial, all of the participants were given 20-mg of oral ruxolitinib, twice daily, for 3 to 6 months. To assess the durability of treatment response, the patients were followed for an additional 3 months.

The results of the trial showed that 9 of the patients had hair regrowth of 50% or greater. By the end of the treatment period, 77% of patients who responded to the therapy achieved hair regrowth of more than 95%.

In the follow-up period, one-third of responders had significant hair loss after the medication was stopped, however, their hair loss did not reach pre-treatment levels.

"Although our study was small, it provides crucial evidence that JAK inhibitors may constitute the first effective treatment for people with alopecia areata,” said researcher Julian Mackay-Wiggan, MD, MS. “This is encouraging news for patients who are coping with physical and emotional effects of this disfiguring autoimmune disease.”

For the study, skin biopsies were performed on each participant before, during, and after treatment. Researchers found that the responders had a reduction in levels of interferon signaling and cytotoxic T lymphocytes, which are indicators of inflammatory response, and higher levels of hair keratins — proteins that indicate hair growth. The levels were similar to those found in people without alopecia areata, according to the study.

Before treatment was started, patients who did not respond to therapy had lower levels of inflammatory signaling, which suggests the possibility of being able to distinguish between responders and nonresponders.

“We are very excited about the use of biomarkers to follow the response of patients to this treatment,” said researcher Angela M. Christiano, PhD, co-author of the tofacitinib paper. “This will allow us to monitor improvements in their gene expression signatures even before hair growth appears.”

In regards to treatment, the drug was found to be well-tolerated in study participants, with no serious adverse events. Those that did occur were infrequent, and included lower hemoglobin levels, bacterial skin infections, and skin allergy symptoms; however, these symptoms were resolved after the dose was adjusted.

“Our findings suggest that initial treatment induces a high rate of disease remissions in patients with moderate to severe alopecia areata but maintenance therapy may be needed,” Mackay-Wiggan said. “While larger, randomized trials are needed to confirm the safety and efficacy of ruxolitinib in people with moderate to severe alopecia areata, our initial results are very encouraging.”

In a different study that used the JAK inhibitor tofacitinib, a series of patients with moderate-to-severe alopecia areata responded to this treatment.

“Together, the 2 studies show that we’re on the right track,” Christiano said.

The next step for the research team is to expand their studies to include the testing of these drugs in other conditions where they may show efficacy, such as androgenetic alopecia, scarring alopecias, and vitiligo.

“We expect JAK inhibitors to have widespread utility across many forms of hair loss based on their mechanism of action in both the hair follicle and immune cells,” Christiano said.