JAK Inhibitors Promising for Alopecia Areata

Marcia Frellick

September 17, 2018

PARIS — Two investigational oral Janus kinase (JAK) inhibitors are safe and effective for patients with moderate to severe hair loss, according to 24-week interim findings from a randomized, double-blind, placebo-controlled, multicenter phase 2 trial.

"I think now our patients with alopecia areata have reason to be optimistic," said investigator Rodney Sinclair, MD, from Sinclair Dermatology in Melbourne, Australia.

Even patients with alopecia totalis — complete hair loss of the scalp — and alopecia universalis — loss of hair on the entire body — responded to PF-06651600 (a JAK3 inhibitor) and PF-06700841 (a JAK1/tyrosine kinase 2 inhibitor), he reported here at the 27th European Academy of Dermatology and Venereology Congress.

Alopecia, the autoimmune disease that affects up to 147 million around the world, is one of the most common presentations at dermatology clinics. However, as yet, there are no reliable treatments, especially for people with severe, chronic disease.

"Although up to 50% of patients recover from an episode either spontaneously or with treatment, 50% don't recover and they continue to have chronic relapsing disease," said Sinclair.

He and his colleagues assessed 115 patients, 18 to 75 years of age, who had alopecia areata for more than 6 months that affected more than 50% of the scalp. One-third of the patients received once-daily PF-06651600 200 mg for 4 weeks followed by a maintenance phase of 50 mg for 20 weeks; one-third received once-daily PF-06700841 60 mg for 4 weeks followed by a maintenance phase of 30 mg for 20 weeks; and one-third received placebo.

The primary efficacy end point was average change in Severity of Alopecia Tool (SALT) score from baseline to week 24.

At week 24, the placebo-adjusted average improvement in SALT score was 33.6% for PF-06651600 (95% confidence interval [CI], 21.4 - 45.7; P < .001) and 49.5% for PF-06700841 (95% CI, 37.1 - 61.8; P < .001). Differences became significant from placebo at week 6 and week 4, respectively.

The secondary end point was the percentage of patients whose SALT score improved from baseline to week 24.

Table. Percentage of Patients With Better SALT Scores at Week 24
Improvement in SALT Score PF-06651600 Group, % PF-06700841 Group, %
30% 47.9 59.6
50% 37.5 48.9
75% 27.0 38.3
90% 25.0 31.9
100% 12.5 12.0


"Importantly, from a patient perspective, a significant number of patients achieved SALT 90 or SALT 100 in the active treatment arms," Sinclair pointed out.

These results are "encouraging," especially because the improvements were seen in those with the most severe forms of alopecia areata, said Jamie MacKelfresh, MD, from the Emory University School of Medicine in Atlanta.

"We need more randomized studies like this, looking at JAK inhibitors in the treatment of alopecia areata," she told Medscape Medical News. "However, the results are still over a relatively short amount of time and in a relatively small number of people. More studies will be needed to establish the use and safety of these medications."

Both JAK inhibitors were well tolerated by the study participants, and there were no cases of herpes zoster reactivation.

Adverse events were similar, and mostly mild, in the three groups. However, two patients in the PF-06700841 group experienced the serious event of rhabdomyolysis. Both discontinued treatment and the adverse effects quickly resolved.

The study was funded by Pfizer. Most of the investigators involved in this study are employed by or are consultants for Pfizer. Sinclair reports ties to Leo Pharma, Amgen, Novartis, Merck, Celgene, Coherus Biosciences, Janssen, Regeneron, MedImmune, GlaxoSmithKline, Cutanea, Samson Clinical, Boehringer Ingelheim, Pfizer, MSD, Oncobiologics, Roche, Eli Lilly, Bayer, and Sun Pharma. MacKelfresh has disclosed no relevant financial relationships.

27th European Academy of Dermatology and Venereology (EADV) Congress: Abstract D3T01. Presented September 15, 2018.

Follow Medscape Dermatology on Twitter @MedscapeDerm and Marcia Frellick @mfrellick


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