JAK3 inhibitors zoom in as potential cure for spot baldness
Treatment with two investigational, oral JAK inhibitors may be beneficial in individuals with moderate‐to‐severe alopecia areata (spot baldness), an autoimmune disease that can cause a lot of anxiety, according to an ongoing phase II study.
Both agents might help fulfill the “unmet need for reliably effective therapy, with a benefit-risk ratio that is appropriate for long-term use in patients with alopecia areata,” said lead investigator Dr Emma Guttman-Yassky from the Icahn Medical School at Mount Sinai in New York, US. Currently, there is no cure for alopecia areata and efforts are directed at speeding hair regrowth through cortisone injections.
In the study, about 60 and 48 percent of patients achieved a 30 percent mean change in the Severity of Especial Tool (SALT) score (the sum of percentage of hair loss in vertex, right profile, left profile and posterior aspect of the scalp) after 24 weeks of treatment with the oral JAK3 inhibitor PF‐06651600 or the oral TYK2/JAK1 inhibitor PF‐06700841. By contrast, there was no improvement among patients on placebo. [ISDS 2018, abstract 125]
On top of that, >12 percent of patients taking either drug achieved a SALT 100 or nearly complete hair restoration of the scalp, said Guttman-Yassky.
Both investigational drugs achieved the primary (mean change from baseline in SALT score) and secondary endpoints (SALT30, 50, 75, 90, 100) at week 24. These benefits were accompanied by significant increases in hair-keratin-associated genes in the biopsy substudy samples, said Guttman-Yassky.
Adverse events were similar in the groups studied at week 24; two had rhabdomyolysis. However, Guttman-Yassky was quick to note that this was only because the two had engaged in heavy exercise and were not removed from the study. No serious adverse events occurred among those on the JAK3 inhibitor or placebo.
In the study, 142 adult patients with alopecia areata affecting ≥50 percent of their scalp were randomized 1:1:1 to the JAK3 inhibitor (200 mg once daily [QD] 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.
At week 24, both agents demonstrated efficacy in achieving the primary endpoint, with statistically significant separation from placebo at week 6 and week 4. SALT mean change from baseline was 33.6 for the JAK 3 inhibitor and 49.5 percent for the TYK2/JAK1 inhibitor, p<0.0001 for both). Of note, participants also reported improvements in eyelash and eyebrow growth and better than placebo (p<0.05).
ISDS session co-chair Dr Erwin Tschachler from the Medical University of Vienna in Vienna, Austria said the study needs to be followed up to determine what would happen after participants discontinue the treatment, and what is the ideal treatment duration for both oral agents.