Hidradenitis Suppurativa: State of the Art

The interleukin-17A/F (IL-17A/F)-targeting nanobody sonelokimab demonstrated high efficacy in patients with moderate-to-severe hidradenitis suppurativa (HS) over 40 weeks. Approximately 30% of patients achieved complete clearance across studies, accompanied by marked improvements in patient-reported disease burden.

Hidradenitis suppurativa (HS) remains one of the most therapeutically challenging conditions in dermatology, with a clear need for novel treatment options. Sonelokimab is a tri-specific nanobody that binds IL-17A and IL-17F and incorporates an anti-albumin moiety to prolong systemic exposure. As Prof. Alexa Kimball (Beth Israel Deaconess Medical Center, MA, USA) explained, the small molecular size of nanobodies may confer enhanced tissue penetration, favourable pharmacokinetics, and potentially improved safety compared with conventional monoclonal antibodies [1]. These properties previously translated into positive phase 2 results in HS, as well as in psoriasis and psoriatic arthritis [2].

The replicate phase 3 VELA-1 (NCT06411899) and VELA-2 (NCT06411379) trials randomised 838 adults with moderate-to-severe HS in a 2:1 ratio to sonelokimab or placebo. The primary endpoint, Hidradenitis Suppurativa Clinical Response by at least 75% (HiSCR75) at week 16, was achieved by approximately one-third of sonelokimab-treated patients, compared with 18%–25% in the placebo group. The current interim analysis extended follow-up to week 40 and included monthly maintenance dosing.

At week 40, 62% of patients achieved HiSCR75 across both trials, while 74%–79% reached HiSCR50. Deeper responses were also observed, with HiSCR90 achieved by 36%–40% of patients and complete clearance (HiSCR100) by approximately 30% of the pooled population. Lesion-specific analyses demonstrated reductions of 71–75% in inflammatory nodules, 72–79% in abscesses, and 60–69% in draining tunnels.

Patient-reported outcomes mirrored these clinical improvements. At baseline, 59% of patients were classified as having “very severe” disease according to the Hidradenitis Suppurativa Quality of Life (HiSQOL) measure; by week 40, 63% had improved to “mild or none.”

Tolerability remained favourable. Although the full 52-week safety data are pending, week 16 results showed serious treatment-emergent adverse events in 2.5% of sonelokimab-treated patients. The most common adverse events were nasopharyngitis (8.6%) and oral candidiasis (7.3%). Follow-up to week 52 is ongoing, alongside a long-term extension of the VELA programme and a separate trial in adolescents (12–17 years). Notably, up to 43% of patients experienced a marked reduction in pain.

With monthly dosing, biologic-comparable HiSCR100 rates of approximately 30%, and consistent improvements in quality of life, sonelokimab represents a promising option for the long-term management of moderate-to-severe HS.

Kimball A. Sonelokimab in moderate-to-severe hidradenitis suppurativa: 40-week results from the phase III VELA-1 and VELA-2 trials. S034: Late-breaking Research Session 2. AAD 2026, 27–31 March, Denver, CO, USA.
Sayed CJ, et al. J Am Acad Dermatol 2025;93(3) Suppl. AB2221.

Week 54 data from the STOP-HS trial demonstrate sustained and increasing response rates with povorcitinib therapy. Improvements were observed across Hidradenitis Suppurativa Clinical Response (HiSCR), symptom burden, and quality-of-life measures.

In the pivotal STOP-HS1 (NCT05620823) and STOP-HS2 (NCT05620836) trials, the Janus Kinase 1 (JAK1) inhibitor povorcitinib met the primary endpoint of HiSCR50 at week 12 in patients with hidradenitis suppurativa (HS). Given the chronic, relapsing nature of HS, long-term efficacy is a key consideration. Data up to week 54, presented by Dr Martina Porter (Beth Israel Deaconess Medical Center, MA, USA), provided further insight into sustained treatment effects [1].

The 2 studies enrolled 1,227 adult patients with Hurley stage 2 or 3 disease, corresponding to moderate-to-severe HS. Following the 12-week placebo-controlled phase, patients initially assigned to placebo switched to povorcitinib (75 mg or 45 mg once daily), while those already receiving povorcitinib continued their assigned dose during a 42-week extension period.

At baseline, the mean age was 37 years, 62.8% of participants were female, and 35.1% had Hurley stage 3 disease. Patient-reported outcomes included a mean Dermatology Life Quality Index (DLQI) score of 12.9 and a skin pain numerical rating scale (NRS) score of 5.0.

Long-term results showed continued increases in the proportion of patients achieving HiSCR50 through week 54. At week 12, HiSCR50 rates in STOP-HS1 were 40.6% (75 mg), 40.2% (45 mg), and 29.7% (placebo), and in STOP-HS2 were 42.3%, 42.3% and 28.6%, respectively. By week 54, these rates had increased to 61.9% (75 mg) and 60.2% (45 mg) among patients who continued povorcitinib in STOP-HS1, and to 68.1% and 68.3% among those who switched from placebo. Corresponding results in STOP-HS2 were 57.3% and 64.3% for continuous treatment, and 71.4% and 67.5% for those switching from placebo.

Depending on the dose and study group, higher response thresholds were also observed, with HiSCR90 rates ranging from 23.2% to 36.2% and HiSCR100 rates ranging from 17.9% to 29%. Reductions in abscesses, draining tunnels, and inflammatory nodules were sustained through week 54, with 16.1%–20.2% of patients achieving complete clearance of these lesion types.

Patient-reported outcomes showed clinically meaningful improvements, including a ≥3-point reduction in skin pain NRS (40.5%–46.8%) and a ≥4-point decrease in DLQI (59.4%–64.7%).

According to Dr Porter, both doses of povorcitinib were generally well-tolerated through 54 weeks of treatment, with safety data available for over 1,000 treated patients. The most common adverse events were acne, nasopharyngitis, and upper respiratory tract infections. Serious treatment-emergent adverse events (TEAEs) occurred in 3.7%–6.4% of patients. There was 1 fatal TEAE, 1 case of major adverse cardiovascular event, 8 thromboembolic events, and 23 cases of herpes zoster; no malignancies were reported.

Porter ML, et al. Povorcitinib in patients with moderate to severe hidradenitis suppurativa: 54-week efficacy and safety results from the STOP-HS1 & STOP-HS2 phase 3 studies. S034 Late-Breaking Research: Session 2. AAD 2026, 27–31 March, Denver, CO, USA.

Sonelokimab delivers deep skin clearance and improves the quality of life in HS patients

HS: Extended povorcitinib treatment yields progressive responses through 54 weeks