Filling the HS Treatment Gap: Ruxolitinib Targets Early-Stage Disease

Each June, Hidradenitis Suppurativa (HS) Awareness Week (June 1-7) highlights the substantial clinical burden and quality-of-life impact associated with HS, emphasizing the need for more effective, targeted therapeutic approaches for this chronic inflammatory disease. HS is characterized by recurrent nodules, abscesses, and sinus tract formation that significantly impair quality of life.^1,2 HS pathogenesis involves dysregulation of innate and adaptive immune pathways, including cytokines such as IL-1, IL-17, and tumor necrosis factor α, many of which signal through the JAK/STAT pathway.¹ Although there are no topical therapies approved by the FDA specifically for HS, several agents have demonstrated some clinical efficacy in early-stage disease. Topical clindamycin; benzoyl peroxide (BPO) and clindamycin combination; topical resorcinol; topical corticosteroids; and antiseptic washes all show limited evidence for successful treatment of mild to moderate HS, but none directly target the immunologic pathways.^3-10

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Ruxolitinib cream (Opzelura; Incyte) is a topical selective JAK1/2 inhibitor that has emerged as a potential therapeutic option by targeting multiple inflammatory pathways simultaneously.¹¹ In a 24-week, open-label pilot study involving 10 patients with mild HS (NCT04414514), 5 of the 6 who completed treatment achieved HS clinical response, defined as at least a 50% reduction in inflammatory lesion count without an increase in abscesses or draining fistulas (HiSCR50), by week 16 with favorable tolerability.¹¹ Biopsies showed reductions in STAT signaling and inflammatory markers, indicating target engagement.¹¹

Current FDA-approved biologic treatment options for moderate to severe HS include adalimumab (Humira; AbbVie), secukinumab (Cosentyx; Novartis), and bimekizumab (Bimzelx; UCB), with other systemic therapies being investigated (ie, upadacitinib [Rinvoq; AbbVie], povorcitinib [Incyte]).¹ These treatments are primarily for moderate to severe disease and/or systemic symptoms but carry adverse effects due to their systemic nature.¹ A gap has emerged in the treatment of patients with mild to moderate disease who do not require or tolerate systemic therapy.

The study by Porter et al recently published in the Journal of the American Academy of Dermatology addresses this gap by reporting outcomes of topical ruxolitinib cream use in patients with mild to moderate HS.¹²

Methods of the Study

Porter et al conducted a randomized, double-blind, vehicle-controlled phase 2 clinical trial (NCT05635838) evaluating ruxolitinib 1.5% cream applied twice daily in patients with mild to moderate HS.¹² Participants included adults with Hurley stage I or II disease without extensive sinus tract formation. After the double-blind, vehicle-controlled (DBVC) period, patients could enter the 16-week open-label extension (OLE) period, during which only sites with signs or symptoms (abscess and inflammatory nodule [AN] count ≥1 and/or skin pain numerical rating scale ≥1) were treated twice daily with 1.5% ruxolitinib cream.¹² In the OLE period, 21 patients (87.5%) in the 1.5% ruxolitinib cream group and 26 patients (81.3%) in the crossover group completed treatment.¹²

The primary end point was achievement of HiSCR50.¹² Secondary end points included changes in abscess and nodule counts, patient-reported outcomes, and histologic markers of inflammation. Safety assessments included monitoring for adverse events, local skin reactions, and laboratory abnormalities.¹²

Results of the Study

In total, 69 patients were randomly assigned and included in the study. The mean age was 29; 50.7% had Hurley stage I, and 49.3% had Hurley stage II. A change from baseline in AN count was significantly reduced with 1.5% ruxolitinib cream vs vehicle at week 16 (least squares mean, –3.61 vs –2.42; P=.0215). There was sustained improvement through week 32 with as-needed use. At week 32, response rates among patients who switched to ruxolitinib cream were similar to those initially randomly assigned to ruxolitinib cream (AN50, 88.5% vs 81.0%; AN75, 61.5% vs 66.7%; AN90/100, 38.5% vs 19.0%).

In addition, more patients achieved HiSCR50 with ruxolitinib cream at week 16 than with vehicle (79.2% vs 50.0%). At week 32, a similar proportion of patients who switched from vehicle for the OLE achieved HiSCR50 as those who were initially randomly assigned to ruxolitinib cream (88.5% vs 81.0%). There was a similar trend for HiSCR75 (ruxolitinib cream vs vehicle at week 16, 54.2% vs 25.0%, vehicle to ruxolitinib cream vs ruxolitinib cream at week 32, 61.5% vs 66.7%).

A numerically greater mean change from baseline in International Hidradenitis Suppurativa Severity Score System (IHS4) results was also observed with ruxolitinib cream vs vehicle at week 16 (−4.46 vs −2.66). Patients who switched to ruxolitinib cream in the OLE had similar improvements at week 32 compared with those initially randomly assigned to ruxolitinib cream (−4.50 vs −4.10). Skin pain and itch improvements were similar between the 2 groups, with about a 2-point increase.

The safety profile of ruxolitinib cream was favorable, with most adverse events being mild and localized. Common adverse effects included application site reactions and upper respiratory infections, with no significant systemic safety signals observed. Three patients discontinued ruxolitinib cream owing to adverse effects: 2 during the DBVC period due to contact dermatitis and hidradenitis, and the other during the OLE period due to a mammary fistula. No major cardiovascular adverse events were reported.

What Does This Mean for Patients?

This study demonstrates that topical ruxolitinib can be highly effective and well tolerated in patients with mild to moderate HS. As there are limited topical treatment options and no FDA-approved agents specifically for mild to moderate HS, topical ruxolitinib has the potential to be a favorable treatment option.

Prior topical agents for mild to moderate HS show some limited efficacy. Topical clindamycin 1% is the most widely studied topical agent in HS but has mainly demonstrated reduction in pustules, not inflammatory nodules or abscesses, and carries a risk of bacterial resistance.^3,4 To reduce resistance and possibly enhance efficacy, combination therapy with clindamycin and BPO has been explored with some efficacy, but has been studied in limited patient populations.⁶ Topical resorcinol has reported efficacy, yet larger prospective studies are needed.^7-9 Topical and intralesional corticosteroids are occasionally used to suppress local inflammation, although evidence is largely anecdotal.¹⁰ Antiseptic washes (ie, chlorhexidine, BPO) are recommended for hygiene and bacterial load reduction, yet lack formal trial data in HS.¹⁰

Several biologic therapies are available for those with moderate to severe disease burden, including adalimumab, secukinumab, and bimekizumab.¹ Systemic JAK inhibitors (ie, upadacitinib, povorcitinib) are in trials and have demonstrated efficacy for moderate to severe HS.^1,13 These therapies come with adverse effects and have limited evidence in mild to moderate disease.

Building on the current biologic therapies, the present study by Porter et alsuggests topical ruxolitinib is an effective treatment for mild to moderate HS.¹²

“This phase 2 study is important because it moves the HS treatment conversation earlier in the disease course. For patients with Hurley I/II disease without draining tunnels, ruxolitinib cream showed reductions in inflammatory lesions, fewer flares, sustained benefit, and a reassuring safety profile. This study supports further investigation of topical JAK inhibition as a targeted, nonantibiotic approach for milder HS, and phase 3 trials are ongoing,” said Melinda Gooderham, MD, FAAD, dermatologist and medical director at SKiN Centre for Dermatology in Peterborough, Ontario, Canada, and senior author of the study, in a statement.

This positions topical ruxolitinib as a first-in-class therapy for patients with mild to moderate HS. The favorable safety profile of topical ruxolitinib cream makes it an attractive option for patients who may not be candidates for systemic therapies or who prefer to avoid systemic immunosuppression.

Conclusion

This phase 2 trial of topical ruxolitinib cream demonstrates promising efficacy and safety in patients with mild to moderate HS, addressing a significant unmet need in the management of early-stage disease. By targeting the JAK/STAT pathway, topical ruxolitinib provides a novel mechanism of action to treat HS that may offer advantages over traditional topical therapies. These findings suggest that topical JAK inhibition could play a transformative role in HS management, particularly for patients with limited disease who require effective, well-tolerated treatment options. Phase 3 trials and real-world studies will be vital to build on these results and help define the ideal role of ruxolitinib cream within the HS treatment paradigm.

Joshua Burshtein, MD, is a resident physician in the Department of Dermatology at the University of Illinois College of Medicine.

References

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11. Schell SL, Sennett ML, Feehan RP, et al. Pilot study of topical ruxolitinib demonstrates efficacy and blunting of heterogeneous inflammatory processes in mild hidradenitis suppurativa. Br J Dermatol. 2025;192(5):845-856. doi:10.1093/bjd/ljae495
12. Porter ML, Ferreira-Cornwell MC, Wang M, Nawaz H, Gooderham MJ. Efficacy and safety of ruxolitinib cream in patients with mild to moderate hidradenitis suppurativa: results from a randomized, double-blind, vehicle-controlled phase 2 study. J Am Acad Dermatol. 2026;94(3):879-887. doi:10.1016/j.jaad.2025.10.149
13. Heidari A, Ghane Y, Heidari N, Sadeghi S, Goodarzi A. A systematic review of Janus kinase inhibitors and spleen tyrosine kinase inhibitors for hidradenitis suppurativa treatment. Int Immunopharmacol. 2024;127:111435. doi:10.1016/j.intimp.2023.111435