Vunakizumab for Radiographic Axial Spondyloarthritis: A Randomized Clinical Trial.

Importance: A notable proportion of patients with ankylosing spondylitis (ie, radiographic axial spondyloarthritis [r-axSpA]) experience either inadequate responses or intolerance to available therapies, highlighting the need for additional treatment options that offer sustained disease control. Objective: To evaluate the efficacy and safety of vunakizumab, a novel anti-interleukin (IL) 17A monoclonal antibody, in r-axSpA. Design, Setting, and Participants: This randomized, double-blind, placebo-controlled, phase 2 to 3 clinical trial was conducted in 38 hospitals in China. A total of 548 adult patients (aged ≥18 years) with active r-axSpA were enrolled between June 9, 2021, and March 30, 2023. Data were analyzed from November 3, 2023, to January 14, 2024. Interventions: In phase 2, patients were randomized 2:2:1 to receive a subcutaneous dose of vunakizumab, 120 mg, vunakizumab, 240 mg, or placebo; vunakizumab, 120 mg was determined to be the recommended dose after interim analysis. In phase 3, patients were randomized 2:1 to receive vunakizumab, 120 mg or placebo at weeks 0, 2, 4, 8, and 12; from week 16, all patients received vunakizumab, 120 mg every 4 weeks through week 32. Main Outcomes and Measures: The primary end point was the proportion of patients with improvement of 20% or greater in Assessment of Spondyloarthritis International Society response criteria (ASAS20) at week 16. Secondary end points were ASAS20 at week 32, improvement of 40% or greater in ASAS response criteria (ASAS40) at weeks 16 and 32, improvement of 20% or greater in 5 of 6 ASAS domains (ASAS5/6) at weeks 16 and 32, and changes from baseline at weeks 16 and 32 in Bath Ankylosing Spondylitis Disease Activity Index score, Bath Ankylosing Spondylitis Functional Index score, Bath Ankylosing Spondylitis Metrology Index score, 36-Item Short Form Survey score, and Ankylosing Spondylitis Quality of Life Questionnaire score. Results: During the entire study, 548 patients were randomized (mean [SD] age, 33.0 [8.9] years; 440 [80.3%] male), including 294 receiving vunakizumab, 120 mg and 146 receiving placebo. At week 16, the ASAS20 response rate was significantly higher with vunakizumab, 120 mg vs placebo (193 [65.6%] vs 62 [42.5%], respectively; difference, 23.2% [95% CI, 11.8%-34.0%]; P < .001); the ASAS40 response rate also favored vunakizumab, 120 mg vs placebo (136 [46.3%] vs 35 [24.0%], respectively; difference, 22.3% [95% CI, 13.3%-31.3%]; P < .001). Responses with vunakizumab were sustained through 32 weeks. During the placebo-controlled period, incidence of adverse events (246 [83.7%] vs 119 [81.5%]) were comparable in the vunakizumab, 120 mg and placebo groups. Conclusions and Relevance: In this randomized clinical trial of patients with r-axSpA, vunakizumab, 120 mg significantly improved signs and symptoms of r-axSpA at week 16 compared with placebo, with sustained efficacy through 32 weeks, and demonstrated a tolerable safety profile. These findings support vunakizumab, 120 mg as a new treatment option for active r-axSpA. Trial Registration: ClinicalTrials.gov Identifier: NCT04840485.