VIENNA — Treatment with two novel oral JAK inhibitors showed promise in patients with moderate‐to‐severe alopecia areata, researchers reported here.
After 24 weeks of treatment with an oral JAK3 inhibitor (PF‐06651600) or an oral TYK2/JAK1 inhibitor (PF‐06700841), about 60% and about 48% of patients achieved a 30% mean change in the Severity of Especial Tool (SALT) score (P<0.001), respectively, versus no improvement among patients on placebo, according to Emma Guttman-Yassky, MD, PhD, of the the Icahn Medical School at Mount Sinai in New York, and colleagues.
Also, >12% of patients taking either drug achieved a SALT 100 or nearly complete hair restoration of the scalp, she said in a presentation at the Inflammatory Skin Disease Summit (ISDS).
Both agents “achieved the study’s primary and secondary endpoint. The clinical effects of both drugs were accompanied by significant increases in hair-keratin-associated genes in the biopsy substudy samples,” Guttman-Yassky stated. However, she pointed out that the agents were compared with placebo, and not with each other.
In addition, “the number of patients with adverse events was comparable across all groups,” she said. Specifically, two patients taking the TYK2/JAK1 inhibitor were diagnosed with rhabdomyolysis, but Guttman-Yassky also noted that those patients engaged in heavy exercise, and they did not have to be removed from the study. There were no serious adverse events observed among the patients on the JAK3 inhibitor or on placebo.
For the ongoing phase II trial, 142 adult patients with alopecia areata affecting ≥50% of their scalp were randomized 1:1:1 to receive the JAK3 inhibitor (200 mg once daily for 4 weeks, followed by 50 mg QD for 20 weeks), or the TYK2/JAK1 inhibitor (60 mg QD for 4 weeks, followed by 30 mg QD for 20 weeks), or placebo.
The researchers reported that, at week 24, both agents demonstrated efficacy in achieving the primary endpoint, with statistically significant separation from placebo at week 6 and week 4:
- JAK3 inhibitor: SALT mean change from baseline (CFB) 33.6 (95% CI 21.4, 43.7, P<0.0001)
- TYK2/JAK1 inhibitor: SALT mean CFB 49.5 (95% CI 37.1, 61.8, P<0.0001)
Guttman-Yassky said patients also reported improvements in eyelash and eyebrow growth, and both agents were significantly better than placebo (P<0.05).
She suggested that the agents might fulfill the “unmet need for a reliably effective therapy with a benefit-risk ratio that is appropriate for long-term use in patients with alopecia areata.”
ISDS session co-chair Erwin Tschachler, MD, of the Medical University of Vienna, told MedPage Today, “This is an important study that needs to be pursued to find out what happens after you discontinue treatment, and how long can you give treatment to these patients… what we need to know about the patients taking these drugs is what will happen to them in 2 years?”
The study was supported by Pfizer.
Guttman-Yassky disclosed relevant relationships with AbbVie, Allergan, Amgen, Asana Biosciences, Celgene, Concert, Dermavant, Dermira, DS Biopharma, Eli Lilly, EMD Serono, Escalier, Fix Bio, Galderma, Glenmark, Innovaderm Research, Janssen, Kyowa, LEO Pharma, Mitsubishi Tanabe, Novan, Novartis, Pfizer, Ralexar Therapeutics, Regeneron, Sanofi-Aventis, and Union Therapeutics.
Tschachler disclosed no relelvant relationships with industry.