PARIS — Interim data from two pivotal phase 3 trials, STOP-HS1 and STOP-HS2, further support the JAK inhibitor povorcitinib as a potential treatment for moderate-to-severe hidradenitis suppurativa (HS).

“These are the largest studies of JAK inhibition in HS to date,” said Martina Porter, MD, who presented the interim findings from the identically designed trials here at the European Academy of Dermatology and Venereology 2025 Congress.

Porter, a dermatologist at Beth Israel Deaconess Medical Center and an assistant professor at Harvard Medical School in Boston, presented primary endpoint data from the 12-week placebo-controlled portion of the trials and some interim findings from the first 12 weeks of the extended follow-up period. 

At 12 weeks, HiSCR50 (HS clinical response: 50% reduction in inflammatory lesions from baseline) occurred in around 40% of participants who were randomized to once-daily treatment with povorcitinib 45 mg or 75 mg. Only about 28% of the placebo-treated patients met this endpoint. 

At 24 weeks, halfway through the trials’ planned extension phases, HiSCR50 was seen in around 60% of participants who had continued povorcitinib at either dose and in around 54% of those who had been switched to povorcitinib after placebo.

Porter reported that the higher dose of povorcitinib was “especially effective in achieving early responses as well as higher thresholds of clinical outcomes such as HiSCR100 and dT 100 [100% reduction/resolution of draining tunnels] through week 24,” and that “both doses were well tolerated with a very low frequency of lab abnormalities.” 

“Considering so far we only have biologics to use,” she said, “I think this is a very promising therapy and could be very impactful for our patients going forward.”

First JAK Inhibitor for HS?

According to a press release issued by povorcitinib’s developer, Incyte Corporation, these data support the planned regulatory submissions for povorcitinib in HS in Europe in 2025 and the United States in early 2026. 

Currently, there are no JAK inhibitors approved for use in the treatment of HS in Europe, although several are approved for other dermatological uses: ruxolitinib (Opzelura) cream for nonsegmental vitiligo; delgocitinib (Anzupgo) cream for chronic hand eczema; baricitinib (Olumiant), upadacitinib (Rinvoq), and abrocitinib (Cibinqo) for atopic dermatitis; ritlecitinib (Litfulo) and baricitinib for alopecia areata; and deucravacitinib (Sotyktu) for psoriasis.

Commenting to Medscape Medical News, Zenas Yiu, MBChB, PhD, clinical senior lecturer in dermatology and pharmacoepidemiology at the University of Manchester and honorary consultant dermatologist for the Northern Care Alliance NHS Foundation Trust in Salford, UK, said, “I am hoping JAK inhibitors will become a valuable addition to our treatment options for hidradenitis suppurativa, which is such a difficult condition to treat.” 

Yiu added that, “I anticipate it will be used as an option after adalimumab should it be approved. With the current paucity of options, any treatment with demonstrable efficacy would be helpful to be trialed.”

Yiu pointed out that povorcitinib targets JAK1, “which is a more broad-reaching target with potentially more downstream effects than the biologics which target either one or two cytokines on the pathway. In a heterogenous condition such as HS, this is welcomed.” 

The STOP-HS Trials

Altogether, STOP-HS1 and STOP-HS2 included 1227 adult patients with moderate-to-severe HS who were recruited across Europe, North America, and Japan from almost 200 sites.

For inclusion, the study participants must have had a diagnosis of moderate-to-severe HS defined as an abscess and inflammatory nodule count of five or more in two or more areas and be at Hurley stage II or III. They also must have received a diagnosis at least 3 months before the trial and been given systemic therapy with oral antibiotics or biologics. 

Participants were randomly allocated equally to start once-daily treatment with either povorcitinib 45 mg, povorcitinib 75 mg, or placebo. After an initial 12-week double-blind phase, patients were rerandomized to either continue their original dose of povorcitinib or, if they had been started on placebo, to now receive one or other dose of povorcitinib for an additional 42 weeks. 

Overall, the median age of participants was around 37 years, about 62% were women, nearly three-quarters were White, 14% were Black, and 12% were other ethnicities. 

In STOP-HS1, the percentage of povorcitinib-treated patients achieving HiSCR50 at 12 weeks was 40.2% (vs 29.7% for placebo; P = .024); at 24 weeks, it was 52.9% for those who switched from placebo and 64.0% for those who had continued povorcitinib 45 mg treatment. Corresponding values for those taking the 75 mg dose were 40.6% (vs 29.7% for placebo; P = .0214) at 12 weeks and 50.0% and 62.7% at 24 weeks. 

Similar results were obtained in the STOP-HS2 trial with both the 45 mg (42.3% vs 28.6% for placebo; P = .0035 at 12 weeks; 57.1% and 58.0% at 24 weeks) and 75 mg (42.3% vs 28.6% for placebo; P = .0033 at 12 weeks; 56.3% and 58.5% at 24 weeks) doses at 12 and 24 weeks, respectively. 

HiSCR75 was achieved by around 24% of povorcitinib-treated patients and about 15% placebo-treated patients at 12 weeks, but this result was only significant in the STOP-HS2 trial. 

Porter reported that, across both trials, povorcitinib treatment was associated with continued improvements at week 24, which was particularly noticeable with the 75 mg dose: HiSCR75 was achieved by 31.0%-40.3%, HiSCR90 by 13.8%-27.7%, and HiSCR100 by 9.2%-21.3%.

More povorcitinib- than placebo-treated patients also achieved at least a three-point decrease from baseline in a skin pain numerical rating score at 3 and 12 weeks, at 17.4% and 22.6% for 45 mg dose, 14.8% and 21.1% for the 75 mg dose, and 6% and 10% for placebo.

The mean change in dT from baseline to 3 weeks and baseline to 12 weeks in the STOP-HS1 were -24.7 and -28.6 for the 45-mg dose, respectively, -27.8 and -37.2 for the 75-mg dose, and -8.2 and -10.4 for placebo. Respective values in the STOP-HS2 trial were -20.5 and -42.9, -27.0 and -42.7, and -1.4 and -15.0.

Porter added that during the placebo-controlled period there were significantly fewer flares in HS among people treated with povorcitinib (20.7%-26.2%) vs placebo (33.5%-33.7%).

The most frequent treatment-emergent events were acne, headache, and nasopharyngitis.

Yiu told Medscape Medical News that the HiSCR50 difference at week 12 was modest (10%-12%) and that this time point may be too early to judge the full effect. He also flagged a methodological concern: The trials used nonresponder imputation through week 12 but switched to as‑observed analyses for weeks 12-24, after the sample size fell (STOP‑HS1: 608 → 482; STOP‑HS2: 619 → 488). He explained that inconsistency can bias the extension results in favor of the intervention and may account for the unexpectedly large crossover gains (20% between weeks 12-24). Yiu recommended using consistent methods — for example, multiple imputation — to preserve an intention‑to‑treat estimate and make the extension data interpretable.

The STOP-HS1 and STOP-HS2 studies were funded by Incyte Corporation. Porter acknowledged receiving research grants or funding, and honoraria or consultation fees from Incyte and many other pharmaceutical and biopharmaceutical companies including: AbbVie, Alumis, AnaptysBio, Arcutis, Avalo, Bayer, Bristol-Myers Squibb, Eli Lilly & Company, FIDE, Janssen Pharmaceuticals, Merck, MoonLake Immunotherapeutics AG, Navigator Biosciences, Novartis, Oasis Pharmaceuticals, Pfizer, Prometheus Laboratories, Regeneron, Sonoma Biotherapeutics, Sanofi, Sonoma Biotherapeutic, Trifecta Clinical/WCG, UCB, and ZuraBio. 

Yiu reported no relevant financial relationships. 

Sara Freeman is a freelance medical journalist based in London, England.