Novel JAK inhibitor induces ‘dose-related’ response in alopecia areata
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Higher doses of a novel Janus kinase inhibitor were associated with improved response over 24 weeks in a cohort of patients with alopecia areata, according to a study.
Brett King, MD, PhD, of the department of dermatology at Yale University School of Medicine in New Haven, Connecticut, explained why Janus kinase (JAK) activation using drugs such as CTP-543 (deuruxolitinib, Concert Pharmaceuticals) may have a pathological role in alopecia areata (AA).
“Messaging between hair follicles and T cells in AA happens via interferon-gamma and interleukin (IL)-15, among other cytokines, which signal through the JAK-STAT pathway,” King told Healio. “JAK inhibitors modulate the activity of interferon-gamma and IL-15, meaning they interrupt the messaging that makes hair loss happen, leading to hair regrowth in AA.”
In the phase 2, randomized, double-blind, placebo-controlled, sequential-design study, King and colleagues investigated oral CTP-543, a deuterated compound that selectively inhibits JAK1 and JAK2, in 149 patients with chronic, moderate to severe AA.
Study protocols called for 30 patients to receive 4 mg of the study drug twice daily, 38 at 8 mg twice daily, 37 at 12 mg twice daily and 44 patients in the placebo group. The treatment duration was 24 weeks.
Results showed that 21% of patients in the 4 mg group, 47% of those in the 8 mg group, 58% of those in the 12 mg group and just 9% of patients in the placebo group reached at least a 50% reduction in Severity of Alopecia Tool (SALT) scores from baseline through 24 weeks.
The researchers noted that this was a “dose-related increase” in efficacy of CTP-543 with a statistically significant increase in response compared with placebo in the 8 mg and 12 mg groups (P < .001).
“Deuruxolitinib at doses of 8 mg and 12 mg twice daily is effective,” King said. “These results are supported by readouts from two phase 3 clinical trials.”
Response began as early as 12 weeks after treatment initiation for the two higher doses, according to the findings.
Safety data showed no new events apart from those conventionally attributed to JAK inhibitors.
“Deuruxolitinib works great for treatment of AA, and it will be exciting to see both longer-term data and dose down-titration data,” King said. “As for safety, the results the current study raise look good but, of course, longer term data in more people are necessary to better understand the safety profile.”