Department for Internal Medicine I, University Hospital Schleswig-Holstein, Kiel, Germany.
Gastroenterology Department, Chaim Sheba Medical Center and Sackler School of Medicine, Tel Aviv University, Tel-Hashomer, Israel.
Gastroenterology. 2021 Jun;160(7):2340-2353. doi: 10.1053/j.gastro.2021.02.068. Epub 2021 Mar 5.
BACKGROUND & AIMS: This study compared pharmacokinetics, symptomatic and endoscopic efficacy, safety, and immunogenicity of a subcutaneous formulation of the infliximab biosimilar CT-P13 (CT-P13 SC) vs intravenous CT-P13 (CT-P13 IV) in patients with inflammatory bowel disease (IBD).
This randomized, multicenter, open-label, parallel-group, phase 1 study enrolled tumor necrosis factor inhibitor-naïve patients with active ulcerative colitis (total Mayo score 6-12 points with endoscopic subscore ≥2) or Crohn's disease (Crohn's Disease Activity Index 220-450 points) at 50 centers. After CT-P13 IV induction at Week (W) 0/W2, patients were randomized (1:1) to receive CT-P13 SC every 2 weeks (q2w) from W6 to W54 or CT-P13 IV every 8 weeks from W6 to W22. At W30, all patients receiving CT-P13 IV switched to CT-P13 SC q2w until W54. The primary endpoint was noninferiority of CT-P13 SC to CT-P13 IV for observed predose CT-P13 concentration at W22 (C), concluded if the lower bound of the 2-sided 90% confidence interval (CI) for the ratio of geometric least-squares means exceeded 80%.
Overall, 66 and 65 patients were randomized to CT-P13 SC and CT-P13 IV, respectively. The primary endpoint of noninferiority was met with a geometric least-squares means ratio for C of 1154.17% (90% CI 786.37-1694.00; n = 59 [CT-P13 SC]; n = 57 [CT-P13 IV]). W30/W54 clinical remission rates were comparable between arms. Other efficacy, safety, and immunogenicity assessments were also broadly comparable between arms, including after switching.
The pharmacokinetic noninferiority of CT-P13 SC to CT-P13 IV, and the comparable efficacy, safety, and immunogenicity profiles, support the potential suitability of CT-P13 SC treatment in IBD. ClinicalTrials.gov ID: NCT02883452.
本研究比较了英夫利昔单抗生物类似药 CT-P13 的皮下制剂（CT-P13 SC）与静脉 CT-P13（CT-P13 IV）在炎症性肠病（IBD）患者中的药代动力学、症状和内镜疗效、安全性和免疫原性。
这是一项随机、多中心、开放性、平行组、Ⅰ期研究，共纳入 50 个中心的肿瘤坏死因子抑制剂初治活动期溃疡性结肠炎（总 Mayo 评分 6-12 分，内镜亚评分≥2）或克罗恩病（克罗恩病活动指数 220-450 分）患者。在 CT-P13 IV 诱导治疗第 0 周（W0）/第 2 周（W2）后，患者按 1:1 比例随机（W6 至 W54 时接受 CT-P13 SC 每 2 周[q2w]治疗；W6 至 W22 时接受 CT-P13 IV 每 8 周治疗）。在 W30 时，所有接受 CT-P13 IV 治疗的患者均转换为 CT-P13 SC q2w 治疗直至 W54。主要终点是 CT-P13 SC 与 CT-P13 IV 在 W22 时观察到的预给药 CT-P13 浓度（C）的非劣效性，如果双侧 90%置信区间（CI）的下限比值超过 80%，则认为该终点达到。
总体而言，66 例和 65 例患者分别被随机分配至 CT-P13 SC 组和 CT-P13 IV 组。C 的几何均数比值为 1154.17%（90%CI 786.37-1694.00；n=59 [CT-P13 SC]；n=57 [CT-P13 IV]），达到了主要终点的非劣效性。W30/W54 临床缓解率在两组间相当。其他疗效、安全性和免疫原性评估结果在两组间也大致相当，包括转换治疗后。
CT-P13 SC 与 CT-P13 IV 的药代动力学非劣效性，以及相当的疗效、安全性和免疫原性特征，支持 CT-P13 SC 治疗 IBD 的潜在适用性。临床试验注册号：NCT02883452。
