SCOTTSDALE, ARIZ. – The Janus kinase (JAK) inhibitor tofacitinib dramatically improved several cases of alopecia areata (AA), although some patients relapsed to worse than baseline after completing treatment in a small open label pilot trial.
“Regrowth was demonstrated in 11 out of 12 patients on tofacitinib. Seven out of 12 patients achieved more than 50% regrowth,” Dr. Shawn Sidharthan reported at the annual meeting of the Society for Investigative Dermatology.
Worldwide, alopecia areata, which is caused by immune-mediated destruction of hair follicles, has a lifetime incidence of about 2% (Clin Cosmet Investig Dermatol. 2015;8:397-403). But there are no Food and Drug Administration–approved treatments for AA. Tofacitinib (Xeljanz), which is approved by the FDA for moderate to severe rheumatoid arthritis in adults, is a JAK1 and JAK3 inhibitor that curbs the interferon-gamma response inflammatory pathway, said Dr. Sidharthan of the department of dermatology and genetics at Columbia University, New York.
AA shares the same interferon response pathway, and tofacitinib prevented alopecia in mice and led to hair regrowth in a patient with alopecia universalis, he noted.
The single-arm trial included seven patients with moderate to severe patchy AA and five patients with alopecia totalis or alopecia universalis. Patients were treated for 6 months. They initially received 5 mg tofacitinib orally twice daily, which was increased to 10 mg twice daily to improve response. The investigators evaluated patients based on SALT (Severity of Alopecia Tool) scores and the Alopecia Areata Disease Activity Index (ALADIN), which uses three-dimensional bioinformatics to identify groups of genes linked to alopecia.
Seven of 12 patients experienced at least 50% regrowth, including six patients who only improved on 10 mg tofacitinib twice daily, Dr. Sidharthan said. Three additional patients “had good regrowth, but not 50%,” he reported. Among the two remaining patients, one had full regrowth, but dropped out of the study because of uncontrolled hypertension, and one patient with alopecia universalis had little or no regrowth.
Notably, two patients began shedding hair after stopping tofacitinib during the observation period of the study, and their final SALT scores were worse than baseline, Dr. Sidharthan said.
Laboratory monitoring of the cohort revealed no severe adverse events, but one patient paused treatment because of thrombocytopenia. The patient’s platelet count normalized after 2 weeks off tofacitinib, and remained normal when the dose was gradually increased to 10 mg twice daily. Another patient developed leukocytosis that resolved during the off-treatment observation period. One patient who did not comply with instructions to avoid alcohol had elevated liver function tests and was taken off the study. Two patients experienced self-limiting diarrhea, and one patient developed trace hematuria, Dr. Sidharthan noted.
In the study, ALADIN scores correlated with clinical response, he said.
He and his coinvestigators concluded that the overall results “provide a strong rationale for larger clinical trials using JAK inhibitors in alopecia areata,” he said.
Dr. Sidharthan noted that another oral JAK inhibitor, ruxolitinib (Jakafi), led to nearly full hair regrowth in three patients with alopecia in a Columbia University study (Nat Med. 2014 Sep; 20:1043-9).
The Locks of Love Foundation funded the research. Dr. Sidharthan, a clinical research fellow in dermatology at Columbia, had no disclosures.