Alopecia Areata Breakthrough: Two Studies Suggest JAK inhibitors May Spur Hair Regrowth

Thursday, September 22, 2016 | Research and Publications , Pfizer


Taken together, two new studies suggest that JAK inhibitors may play a role in treating alopecia areata.

Two JAK inhibitors are already approved by the U.S. FDA, XELJANZ® (tofacitinib citrate) for rheumatoid arthritis and Jakavi® (ruxolitinib) for bone marrow malignancies.

In a study of 66 adults with alopecia areata, more than half saw hair regrowth and one-third recovered more than 50 percent of their initial scalp hair loss after three months of taking tofacitinib citrate 5 mg, twice daily.

In a second open-label study out of Columbia University Medical Center (CUMC) in New York City,  75 percent of patients with moderate-to-severe alopecia areata had significant hair regrowth after treatment with ruxolitinib.

Both reports appear in Journal of Clinical Investigation/Insight.

The tofacitinib study builds on earlier work that showed this drug could be used to treat alopecia area. Tofacitinib appears to stop the immune system’s attack on the hair follicle in alopecia areata, the researchers suggest.

 “The only missing pieces are, one, the results of treatment over longer periods of time and, two, looking at treatment of the pediatric age group, where the disease frequently shows up first and can be particularly devastating,” says study author Brett A. King, M.D., a dermatologist at Yale School of Medicine in New Haven, Conn.  “We’ll have those results soon.”

This study was limited by short duration; side effects were mild.

The Ruxolitinib Study

In the second study, twelve patients with moderate-to-severe alopecia areata were given 20 mg of oral ruxolitinib, twice a day, for 3 to 6 months. Participants were followed for an additional 3 months to assess the durability of treatment response.

Nine of the patients had hair regrowth of 50 percent or greater. By the end of the treatment period, 77 percent of those who responded to the therapy achieved hair regrowth of more than 95 percent. A third of the responders had significant hair loss in the follow-up period after the medication was stopped, although 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,” says study author Julian Mackay-Wiggan, MD, MS, associate professor and director of the clinical research unit in dermatology at CUMC and a dermatologist at NewYork-Presbyterian/Columbia.

Previously, the Columbia researchers 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. Subsequent experiments with mouse and human hair follicles showed that JAK inhibitors can reawaken these dormant follicles by blocking inflammatory signaling.

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

Biomarkers for Response IDed

Skin biopsies performed before, during, and after treatment also revealed that responders had a reduction in levels of interferon signaling and cytotoxic T lymphocytes—indicators of an inflammatory response—and higher levels of hair keratins, which are proteins that indicate hair growth. These levels were similar to those in people without alopecia areata.

Before starting treatment, patients who ultimately did not respond to therapy had lower levels of inflammatory signatures, suggesting that it may be possible to distinguish between responders and nonresponders.

“We are very excited about the use of biomarkers to follow the response of patients to this treatment,” says Angela M. Christiano, PhD, the Richard and Mildred Rhodebeck Professor of Dermatology and professor of genetics and development at CUMC. “This will allow us to so monitor improvements in their gene expression signatures even before hair growth appears.”

The drug was well tolerated in all participants, with no serious adverse events.

The CUMC research team now plans to expand their studies to include testing these drugs in other conditions such as vitiligo, scarring alopecias and androgenetic alopecia (pattern baldness) where they may also show efficacy. “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,” says Dr. Christiano.

PHOTO CAPTION: Hair regrowth after ruxolitinib treatment of a patient with alopecia areata.

PHOTO CREDIT:  Lab of Dr. Angela Christiano/Columbia University Medical Center

Next Story

Comments

You must be logged in to leave a comment.