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

Abstract

Hidradenitis suppurativa (HS) is a debilitating inflammatory skin disease with limited therapeutic options. 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. 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. 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. 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. 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. 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. ClinicalTrials.gov Identifier: NCT05139602.