Efficacy and Safety of Recibokibart, an Interleukin-36 Receptor Antibody, in Generalized Pustular Psoriasis: A Phase 2 Randomized Trial.

BACKGROUND: Generalized pustular psoriasis (GPP) is a rare, severe inflammatory skin disease characterized by acute flares. Recibokibart is a humanized IgG1 monoclonal antibody targeting the interleukin-36 (IL-36) receptor. In a phase 1b open-label study, a single intravenous dose of recibokibart was associated with an acceptable safety profile and rapid improvements in pustulation, overall skin disease severity, and systemic inflammatory markers through 12 weeks. OBJECTIVES: This study aimed to evaluate the efficacy and safety of recibokibart in patients with acute flares of GPP. METHODS: In this multicenter, randomized, double-blind, placebo-controlled phase 2 trial conducted in China, patients with moderate-to-severe acute GPP were randomly assigned in a 2:1 ratio to receive a single intravenous dose of recibokibart (1050 mg) or placebo at day 1. Patients with persistent disease activity at day 8 were eligible to receive open-label recibokibart, and patients with recurrent flares after achieving a Generalized Pustular Psoriasis Physician Global Assessment (GPPGA) total score of 0 or 1 could receive an additional open-label dose. The primary efficacy endpoint was the proportion of patients who achieved a GPPGA pustulation sub-score of 0 or 1 at week 1 (day 8). RESULTS: A total of 33 patients were randomized (recibokibart, n=22; placebo, n=11). At week 1 (day 8), the primary endpoint of achieving a GPPGA pustulation sub-score of 0 or 1 was met by 86.4% of patients in the recibokibart group versus 9.1% in the placebo group (between-group difference, 77.3%; 95% CI, 42.5-88.9; P<0.0001). At week 1 (day 8), greater improvements were observed with recibokibart across key secondary endpoints, including achievement of a GPPGA total score of 0 or 1 (63.6% vs. 0%), complete pustule clearance (54.5% vs. 0%), and mean percentage change from baseline in GPPASI (-59.3% vs. 0%). By week 4, 72.7% of patients treated with recibokibart achieved GPPASI 75. Clinical improvements were observed as early as 24 hours after treatment and were maintained through week 12, although assessments after day 8 included patients who received open-label treatment. The most frequently reported adverse events with recibokibart included hypoproteinemia, hypertriglyceridemia, hyperlipidemia, and pruritus. CONCLUSIONS: A single intravenous dose of recibokibart resulted in rapid improvement in pustular and overall skin disease severity in patients with acute GPP flares, with an acceptable safety profile.