Objectives Bimekizumab selectively neutralises both interleukin (IL)-17A and IL-17F. We report efficacy and safety in a phase IIb dose-ranging study in patients with active ankylosing spondylitis (AS). Methods Adults with AS (fulfilling modified New York criteria) were randomised 1:1:1:1:1 to bimekizumab 16 mg, 64 mg, 160 mg, 320 mg or placebo every 4 weeks for 12 weeks (double-blind period). At week 12, patients receiving bimekizumab 16 mg, 64 mg or placebo were re-randomised 1:1 to bimekizumab 160 mg or 320 mg every 4 weeks to week 48; other patients continued on their initial dose (dose-blind period). The primary end point was Assessment of SpondyloArthritis international Society (ASAS) 40 response at week 12 (non-responder imputation (NRI) for missing data). Results 303 patients were randomised: bimekizumab 16 mg (n=61), 64 mg (n=61), 160 mg (n=60), 320 mg (n=61) or placebo (n=60). At week 12, significantly more bimekizumab-treated patients achieved ASAS40 vs placebo (NRI: 29.5%–46.7% vs 13.3%; p<0.05 all comparisons; OR vs placebo 2.6–5.5 (95% CI 1.0 to 12.9)). A significant dose-response was observed (p<0.001). The primary end point was supported by all secondary efficacy outcomes. At week 48, 58.6% and 62.3% of patients receiving bimekizumab 160 and 320 mg throughout the study achieved ASAS40, respectively (NRI); similar ASAS40 response rates were observed in re-randomised patients. During the double-blind period, treatment-emergent adverse events occurred in 26/60 (43.3%) patients receiving placebo and 92/243 (37.9%) receiving bimekizumab. Conclusions Bimekizumab provided rapid and sustained improvements in key outcome measures in patients with active AS, with no unexpected safety findings versus previous studies. Trial registration number NCT02963506.

中文翻译：

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在活动性强直性脊柱炎患者中使用 bimekizumab 对白介素 17A 和白介素 17F 进行双重中和：一项为期 48 周的 IIb 期随机、双盲、安慰剂对照、剂量范围研究的结果

目的 Bimekizumab 选择性地中和白细胞介素 (IL)-17A 和 IL-17F。我们报告了一项针对活动性强直性脊柱炎 (AS) 患者的 IIb 期剂量范围研究的有效性和安全性。方法 将患有 AS（符合改良纽约标准）的成人按 1:1:1:1:1 随机分配至 bimekizumab 16 mg、64 mg、160 mg、320 mg 或安慰剂，每 4 周一次，持续 12 周（双盲期）。在第 12 周，接受 bimekizumab 16 mg、64 mg 或安慰剂的患者每 4 周至 48 周以 1:1 的比例重新随机分配至 bimekizumab 160 mg 或 320 mg；其他患者继续使用他们的初始剂量（剂量盲期）。主要终点是第 12 周时国际脊柱关节炎协会 (ASAS) 40 反应的评估（缺失数据的无反应者插补 (NRI)）。结果 303 名患者被随机分组​​：bimekizumab 16 mg (n=61)、64 mg (n=61)、160 mg (n=60)、320 mg (n=61) 或安慰剂 (n=60)。在第 12 周时，比美克珠单抗治疗的患者达到 ASAS40 的比例明显高于安慰剂（NRI：29.5%–46.7% 对 13.3%；所有比较 p<0.05；OR 对安慰剂 2.6–5.5（95% CI 1.0 到 12.9））。观察到显着的剂量反应（p<0.001）。所有次要疗效结果都支持主要终点。在第 48 周，在整个研究中接受 bimekizumab 160 和 320 mg 的患者中分别有 58.6% 和 62.3% 达到了 ASAS40（NRI）；在重新随机分组的患者中观察到类似的 ASAS40 反应率。在双盲期间，26/60 (43.3%) 接受安慰剂的患者和 92/243 (37.9%) 接受 bimekizumab 的患者发生了治疗中出现的不良事件。结论 Bimekizumab 在活动性 AS 患者的关键结果指标方面提供了快速和持续的改善，与之前的研究相比，没有意外的安全性发现。试验注册号 NCT02963506。