Phase 3 STOP-HS Trials Highlight Promise of Oral JAK1 Inhibition for Moderate to Severe Disease

Martina Porter, MD, vice chair of research and academics in the department of dermatology at Beth Israel Deaconess Medical Center and a dermatologist specializing in hidradenitis suppurativa (HS), discussed the phase 3 STOP-HS1 and STOP-HS2 trials evaluating the investigational oral selective JAK1 inhibitor povorcitinib for patients with moderate to severe HS.

The global phase 3 trials assessed 2 oral doses of povorcitinib (45 mg and 75 mg) with HiSCR50 at week 12 serving as the primary endpoint. Following the placebo-controlled induction period, participants either remained on their assigned active treatment or, if initially randomized to placebo, transitioned to a prespecified active dose through week 54, allowing investigators to evaluate both early and long-term treatment responses.¹

According to Porter, a STOP-HS investigator, one notable aspect of the study design was the exclusion of continuous antibiotic therapy, which has been permitted in several previous HS clinical trials. She also noted that the study population reflected an increasingly treatment-experienced HS population, with many participants having previously received biologic therapies, including TNF-α and IL-17 inhibitors. Compared with earlier pivotal HS trials, such as the PIONEER studies of adalimumab that enrolled biologic-naïve patients, the STOP-HS population likely represented patients with more severe, treatment-refractory disease.

Despite this more challenging patient population, both povorcitinib dose groups achieved statistically significant improvements at the primary endpoint. Approximately 40% of patients receiving either the 45 mg or 75 mg dose achieved HiSCR50 at week 12 compared with just under 30% of patients receiving placebo. 

“I think that means that we should see this drug get FDA approved and also get approved in Europe in the coming year,” Porter told Dermatology Times. “It'll allow us to have a totally different mechanism of action in an oral medication to use for HS, which is something we really don't have now.”

Beyond the primary endpoint, Porter emphasized the importance of evaluating both the timing and magnitude of clinical responses. Patients began achieving HiSCR50 as early as week 3, an outcome she believes is meaningful because early improvement helps reinforce treatment adherence and patient confidence. However, she noted that in clinical practice, a response closer to HiSCR75 is often associated with meaningful patient satisfaction and a greater willingness to continue therapy.

She cautioned that HS should be viewed as a chronic inflammatory disease requiring long-term management rather than rapid disease clearance. While early responses at weeks 3 and 12 are encouraging, maximal benefit with most HS therapies often occurs after 24 to 54 weeks of treatment, with some long-term extension studies demonstrating continued improvement over two to three years. Porter encouraged clinicians to maintain realistic expectations and avoid discontinuing effective therapies prematurely, particularly in patients with longstanding Hurley stage III disease, where meaningful improvement may require sustained treatment over time.

"I always tell patients and other people treating HS that this really, I think, is more of a marathon than a sprint,” she said. “It requires a lot of patience—on us and the patients—to really wait to see some of these improvements.”

Reference

1. Porter ML, Martorell A, Sayed CJ, et al. Povorcitinib for hidradenitis suppurativa: the randomized, double-blind, placebo-controlled STOP-HS1 and STOP-HS2 phase 3 trials. Nat Med. Published online July 23, 2026. doi:10.1038/s41591-026-04534-z