Lutikizumab in Adults With Moderate to Severe Hidradenitis Suppurativa After Anti-TNF Therapy Failure: A Phase 2 Randomized Clinical Trial.

Importance: Hidradenitis suppurativa (HS) is a debilitating inflammatory skin disease with limited therapeutic options. Objective: To assess the efficacy and safety of lutikizumab, a dual-variable domain interleukin 1α/1β antagonist, for adult participants with moderate to severe HS who experienced anti-tumor necrosis factor (TNF) therapy failure. Design, Setting, and Participants: This phase 2, double-blind, placebo-controlled randomized clinical trial was conducted at 45 sites in 8 countries or territories (Australia, Canada, Germany, Greece, Japan, Puerto Rico, Spain, and the US) between December 28, 2021, and November 27, 2023, and included a 35-day screening period, a 16-week treatment period, and a 9-week safety follow-up. Data were analyzed in December 2023. Participants 18 years or older with a diagnosis of HS for 12 months or longer who experienced anti-TNF treatment failure were enrolled. Interventions: Eligible participants were randomized 1:1:1:1 to receive lutikizumab, 300 mg, every week; lutikizumab, 300 mg, every other week; lutikizumab, 100 mg, every other week; or placebo, every week. The trial drug was administered starting at baseline and through week 16. Main Outcomes and Measures: The primary end point was achieving a Hidradenitis Suppurativa Clinical Response (HiSCR 50) at week 16. The secondary efficacy objective was achieving at least a 30% reduction and at least 1-unit reduction from baseline in Patient's Global Assessment of skin pain (Numerical Rating Scale [NRS] 30) after 16 weeks of treatment among among patients with a baseline NRS 3 or greater. Additional end points included achieving HiSCR 75 and HiSCR 90, change and percentage change from baseline in draining tunnels, and change from baseline in Dermatology Life Quality Index total scores. Results: A total of 153 participants received at least 1 dose of the trial medication (94 female individuals [61.4%]; mean [range] age, 40.5 [19-75] years; 108 patients [70.6%] at Hurley stage III). At week 16, 19 (48.7%), 22 (59.5%), and 10 participants (27.0%) receiving lutikizumab, 300 mg, every week; lutikizumab, 300 mg, every other week; and lutikizumab, 100 mg, every other week, respectively, achieved HiSCR50 at week 16 compared with placebo (35.0%); posterior probabilities of positive treatment effect vs placebo were 89.3%, 98.5%, and 22.8%, respectively, using a bayesian analysis. Among participants with baseline NRS scores of 3 or greater, 10 (34.5%) who received lutikizumab, 300 mg, every other week and 8 (34.8%) who received lutikizumab, 300 mg, every week achieved an NRS30 response compared with 4 (12.9%) who received placebo. There were no deaths or treatment-emergent adverse events of neutropenia, serious hypersensitivity reactions, major adverse cardiovascular events, or opportunistic infections reported. Conclusions and Relevance: In this phase 2 randomized clinical trial, lutikizumab, 300 mg, every week and 300 mg every other week showed positive treatment effects vs placebo in a hard-to-treat moderate to severe HS population that experienced anti-TNF therapy failure. Trial Registration: ClinicalTrials.gov Identifier: NCT05139602.