The dual-variable domain interleukin (IL) 1α/1β antagonist lutikizumab improves clinical response and pain in patients with moderate-to-severe hidradenitis suppurativa after the failure of anti-tumour necrosis factor (TNF) therapy, a phase 2 trial has shown.
Conducted across 45 sites in eight countries and published in JAMA Dermatology, the double-blind, placebo-controlled trial aimed to address the limited therapeutic options available for this debilitating inflammatory skin disease.
The trial enrolled 153 adults (mean age 40.5 years; 61.4% female) with clinically diagnosed hidradenitis suppurativa for one year or longer, all of whom had experienced inadequate response, intolerance or loss of response to anti-TNF therapy.
They were randomised to receive lutikizumab 300 mg weekly, 300 mg every other week, 100 mg every other week, or placebo for 16 weeks.
Most participants (70.6%) had severe disease, with a mean abscess and inflammatory nodule count of 18.2 and approximately six draining tunnels at baseline, reflecting a high-burden population.
Efficacy and safety of lutikizumab
Hidradenitis Suppurativa Clinical Response 50 (HiSCR50) was the primary outcome, achieved by 59.5% of patients receiving 300 mg every other week and 48.7% receiving 300 mg weekly, compared with 35.0% in the placebo group.
Secondary outcomes showed consistent benefits. Among participants with baseline pain scores of 3 or higher, 34.5% of patients receiving 300 mg every other week and 34.8% receiving that dose weekly, achieved at least a 30% reduction in the Numerical Rating Scale, compared with 12.9% in the placebo group.
HiSCR75 was achieved in up to 45.9% of patients, and HiSCR90 in up to 25.6% in the higher-dose groups, compared with 17.5% and 5.0%, respectively, with placebo.
Additional improvements included reductions in draining tunnel counts and clinically meaningful improvements in Dermatology Life Quality Index scores, with least-squares mean differences of up to −3.8.
The safety profile of lutikizumab was broadly comparable to the placebo. Treatment-emergent adverse events occurred in 64.9–78.4% of treated patients, compared with 75.0% in the placebo group, and were predominantly mild or moderate.
Serious adverse events were infrequent with no deaths, opportunistic infections, neutropenia, major adverse cardiovascular events or serious hypersensitivity reactions reported.
Clinically meaningful improvements in hidradenitis suppurativa
Notably, the trial focused exclusively on a difficult-to-treat population with prior anti-TNF failure, enhancing the clinical relevance of the findings. However, the authors acknowledged that several limitations should be considered.
The sample size was relatively small, with a limited treatment duration of 16 weeks, which restricted assessment of long-term efficacy and safety. Approximately 20% of the data were missing, and some baseline imbalances between treatment groups may have influenced the comparative outcomes, they said.
Despite these limitations, the authors concluded that dual IL-1α/β neutralisation with lutikizumab delivered clinically meaningful improvements in both objective disease measures and patient-reported outcomes by targeting inflammatory pathways not currently addressed by existing biologics.
Further investigation is warranted, and the authors highlighted that a phase 3 trial is currently underway to assess long-term efficacy, response durability and broader applicability, including in adolescent populations.
Reference
Kimball AB et al. Lutikizumab in adults with moderate to severe hidradenitis suppurativa after anti-TNF therapy failure: a phase 2 randomised clinical trial. JAMA Dermatol 2026;Mar 18:doi:10.1001/jamadermatol.2026.0155.