1441: Efficacy and Safety of Vunakizumab in Patients with Active Ankylosing Spondylitis by Cigarette Smoking Status: A Post Hoc Analysis of a Randomized, Double-blind, Phase 2/3 Study

Background/Purpose: Vunakizumab, a humanized anti-interleukin-17A monoclonal antibody, has shown significant efficacy and favorable safety in patients with active ankylosing spondylitis (AS), leading to its approval in China. This analysis aims to evaluate the impact of cigarette smoking status on the efficacy and safety of vunakizumab in patients with active AS.

Methods: This post hoc analysis used data from a randomized, double-blind, adaptive, seamless, phase 2/3 trial (NCT04840485) of vunakizumab in adult patients with active AS who were confirmed by radiographic evidence and met the modified New York criteria. In phase 2, eligible patients were randomized (2:2:1) to receive subcutaneous vunakizumab 120 mg, 240 mg, or placebo at weeks 0, 2, 4, 8, and 12. In phase 3, patients were randomized (2:1) to receive vunakizumab 120 mg (the optimal dose selected from phase 2) or placebo. In both phases, all patients continued to receive subcutaneous vunakizumab every 4 weeks from week 16 to week 32. The primary endpoint was the proportion of patients with at least 20% improvement in Assessment of SpondyloArthritis International Society (ASAS20) response criteria at week 16. This analysis pooled baseline, efficacy and safety data for patients receiving vunakizumab 120 mg or placebo in phase 2 and 3. Subgroup analyses were performed based on smoking status (never/former smoker or current smoker). Efficacy outcomes included ASAS20, ASAS40 and ASAS5/6. Logistic regression models were used to estimate the treatment difference in each subgroup, with stratification factors (weight, prior exposure to tumor necrosis factor-α inhibitors) as covariates. Safety was also assessed.

Results: A total of 440 patients were included in the analysis. Of these, 279 patients were never/former smokers (vunakizumab, n=182; placebo, n=97), and 161 patients were current smokers (vunakizumab, n=112; placebo, n=49). Baseline demographics and clinical characteristics were comparable between treatment arms within smoking status subgroups. The efficacy outcomes (ASAS20, ASAS40, ASAS5/6) from week 2 to week 16 are presented in Table 1. At week 16, among never/former smokers, the ASAS20 response rates were 67.58% for vunakizumab and 46.39% for placebo (OR: 2.44; 95% confidence interval [CI]: 1.47, 4.06; nominal P=0.0006); among current smokers, the ASAS20 response rates were 62.50% for vunakizumab and 34.69% for placebo (OR: 3.26; 95% CI: 1.61, 6.63; nominal P=0.0011). Moreover, vunakizumab showed a rapid onset of action, with a higher ASAS20 response rate observed as early as week 2 compared to placebo in both subgroups. This elevated ASAS20 response was sustained through week 32 in both subgroups (Figure 1). Furthermore, no treatment-subgroup interaction term was observed for ASAS20, ASAS40 and ASAS5/6 responses from week 2 to week 16 (Table 1). The incidence of treatment-emergent adverse events (TEAEs) was similar across treatment arms within smoking status subgroups. During the 32-week treatment period, the majority of TEAEs were mild to moderate in severity.

Conclusion: Vunakizumab 120 mg showed significant efficacy and favorable safety in patients with active AS, regardless of cigarette smoking status.