Objective To demonstrate clinical equivalence of adalimumab biosimilar candidate BI 695501 with Humira. Methods Patients with active rheumatoid arthritis on stable methotrexate were randomised to BI 695501 or Humira in a double-blind, parallel-group, equivalence study. At week 24, patients were rerandomised to continue BI 695501 or Humira, or switch from Humira to BI 695501. The coprimary endpoints were the percentage of patients achieving the American College of Rheumatology 20% response criteria (ACR20) at weeks 12 and 24. Further efficacy and safety endpoints and immunogenicity were assessed up to week 58. Results 645 patients were randomised. At week 12, 67.0% and 61.1% (90% CI –0.9 to 12.7) of patients receiving BI 695501 (n=324) and Humira (n=321), respectively, achieved ACR20; at week 24 the corresponding values were 69.0% and 64.5% (95% CI –3.4 to 12.5). These differences were within prespecified margins (week 12: 90% CI (–12% to 15%); week 24: 95% CI (−15% to 15%)), demonstrating therapeutic bioequivalence. 593 patients were rerandomised at week 24. Up to week 48, mean change from baseline in Disease Activity Score 28-erythrocyte sedimentation rate and ACR20/ACR50/ACR70 response rates were similar across the switched (n=147), continuous BI 695501 (n=298) and continuous Humira (n=148) groups. Similar immunogenicity (antidrug antibodies (ADAs), ADA titres and neutralising antibodies) was seen between BI 695501 and Humira (to week 24) and across rerandomised groups (to week 48). Safety and tolerability profiles were similar between groups. Conclusions BI 695501 demonstrated similar efficacy, safety and immunogenicity to Humira; switch from Humira to BI 695501 had no impact on efficacy, safety and immunogenicity. Trial registration number NCT02137226, Results.

中文翻译：

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阿达木单抗生物仿制药 BI 695501 和 Humira 参比产品在中度至重度活动性类风湿关节炎患者中的相似疗效、安全性和免疫原性：III 期随机 VOLTAIRE-RA 等效性研究结果


目的 证明阿达木单抗候选生物类似药 BI 695501 与 Humira 的临床等效性。方法 在一项双盲、平行组等效研究中，接受稳定甲氨蝶呤治疗的活动性类风湿关节炎患者被随机分配至 BI 695501 或 Humira 组。在第 24 周，患者被重新随机分配继续使用 BI 695501 或 Humira，或从 Humira 切换到 BI 695501。共同主要终点是在第 12 周和第 24 周达到美国风湿病学会 20% 缓解标准 (ACR20) 的患者百分比。评估疗效和安全性终点以及免疫原性直至第 58 周。结果 645 名患者被随机分组​​。第 12 周时，接受 BI 695501 (n=324) 和 Humira (n=321) 治疗的患者分别有 67.0% 和 61.1% (90% CI –0.9 至 12.7) 达到 ACR20；第 24 周时的相应值为 69.0% 和 64.5%（95% CI –3.4 至 12.5）。这些差异在预先设定的范围内（第 12 周：90% CI（–12% 至 15%）；第 24 周：95% CI（−15% 至 15%）），证明了治疗生物等效性。 593 名患者在第 24 周被重新随机分组。截至第 48 周，疾病活动评分 28-红细胞沉降率和 ACR20/ACR50/ACR70 反应率相对于基线的平均变化在切换组 (n=147)、连续 BI 695501 (n =298) 和连续 Humira (n=148) 组。 BI 695501 和 Humira（至第 24 周）以及重新随机分组（至第 48 周）之间观察到类似的免疫原性（抗药物抗体 (ADA)、ADA 效价和中和抗体）。各组之间的安全性和耐受性相似。结论 BI 695501 表现出与 Humira 相似的功效、安全性和免疫原性；从 Humira 转为 BI 695501 对疗效、安全性和免疫原性没有影响。试验注册号NCT02137226，结果。