Patients with alopecia areata (AA) who do not respond to treatment with one of the three approved JAK inhibitors may get a response by switching to one of the other JAK inhibitors, a small study has shown.

“What dermatologists need to know is that if at first your patient does not successfully grow their hair, then try, try again, of course optimizing treatment from the start,” the corresponding author, Brett King, MD, PhD, dermatologist in Fairfield, Connecticut, told Medscape Medical News. 

The case series, published online as a research letter in JAMA Dermatology, included 13 patients of various ethnicities who did not respond to initial JAK inhibitor therapy, with five moving on to a fourth JAK inhibitor before getting a response. After the second, third, or fourth JAK inhibitor, all patients had a response, measured by achievement of a Severity of Alopecia Tool (SALT) score ≤ 20.

Six patients were started on 5 mg tofacitinib twice daily, two on 10 mg tofacitinib twice daily, three on 50 mg ritlecitinib daily, and two on 4 mg baricitinib daily. For the second round, they were switched to various doses and agents. Two of the patients who started on 5 mg tofacitinib were then given the 10-mg formulation but failed at that, too. Two patients started on 5 mg tofacitinib twice daily switched to 4 mg baricitinib daily for their second JAK inhibitor, with one achieving their treatment goal but the other needing two different doses of upadacitinib — 15 and 30 mg daily — before reaching their SALT goal. None of the patients followed the regimen steps through to treatment response.

The three JAK inhibitors approved by the FDA for AA are baricitinib, ritlecitinib, and deuruxolitinib.

The results may portend the possibility of personalized medicine for aiding treatment decisions in patients with AA, said King, who was previously with the Department of Dermatology, Yale University, New Haven, Connecticut. 

“This work might anticipate a future of personalized medicine when biomolecular analysis of a scalp biopsy details a patient’s response to one or another JAK inhibitor or, hopefully, a list of treatments for alopecia areata,” he added. “At this moment in time, however, we are not there.”

He and the two other authors acknowledged the small sample size but wrote, “our results show successful treatment of AA with several different JAKis [JAK inhibitors] after failure of one, two, or even three other JAKis, which carries important clinical implications: Achieving optimal treatment outcomes will require use of all of the JAKis.”

Two Features Key to AA Treatment

In treating AA, clinicians must keep in mind two clinical features of the disease that help determine treatment response, King told Medscape Medical News.

The first is whether the patient has scalp hair at the start of treatment or begins treatment with no scalp hair. “Up to 60% or more of patients who have scalphair at the start of treatment will grow hair with a JAKi, whereas about 40% of similar patients with no hair at the start of treatment will grow hair,” he said.

The other key feature is how long the patient has had severe hair loss, not necessarily how long they have had AA, when they start treatment. “People who get treatment in the first four years of a severe episode respond better than those who get treatment later than that,” King said. 

“Putting these two clinical features together, patients with hair and duration of current episode of severe loss less than 4 years respond better and faster to treatment than others,” he noted. 

King added that 6 months “and sometimes even 9 months” is the minimum threshold for determining the effectiveness of treatment with any JAK inhibitor, “looking for 30% or more scalp hair regrowth from baseline during that period or regrowth of eyebrows or eyelashes.”

In the study, 85% of the nonresponders also received 2.5-10 mg concomitant oral minoxidil daily. “There is growing evidence supporting that adding oral minoxidil with JAK inhibitor improves efficacy and may accelerate hair growth, and so combination treatment should always be considered,” he said. He cited two small studies — one in adults and the other in pediatric patients — that support this approach.

King reported having financial relationships with Pfizer, AbbVie, Eli Lilly, Sun Pharmaceuticals, AltruBio, Almirall, Amgen, AnaptysBio, Apogee Therapeutics, Aquestive, BiologicsMD, Bristol Myers Squibb, Equillium, Galderma, GSK, Incyte Corp., Janssen Pharmaceuticals, LEO Pharma, Merck, Novartis, Otsuka/Visterra, Q32 Bio, Regeneron, Sanofi Genzyme, Soterios, Takeda, TWi Biotechnology, and Ventyx Biosciences. One of the other authors reported receiving honoraria and fees from Pfizer; another author reported receiving honoraria and fees from AbbVie, Arcutis, BiologicsMD, Dermavant, Incyte, Eli Lilly, LEO Pharma, GSK, Novartis, Pfizer, Regeneron, Sanofi Genzyme, Takeda, and Sun Pharmaceuticals outside the submitted work.

Richard Mark Kirkner is a medical journalist based in Philadelphia.