Department of Rheumatology, Peking Union Medical College Hospital, Peking Union Medical College and Chinese Academy of Medical Sciences, No. 1 Shuaifuyuan, Dongcheng District, Beijing, 100730, China.
National Clinical Research Center for Immunologic Diseases, Ministry of Science and Technology, No. 1 Shuaifuyuan, Dongcheng District, Beijing, 100730, China.
BioDrugs. 2020 Jun;34(3):381-393. doi: 10.1007/s40259-020-00408-z.
The aim of this study was to evaluate the efficacy and safety of the biosimilar candidate of adalimumab (HS016) compared with adalimumab (Humira) for the treatment of active ankylosing spondylitis.
A multicenter, randomized, double-blind, parallel, positive control, phase III clinical trial was conducted at 28 locations in China. Patients with active ankylosing spondylitis were randomized in a 2:1 ratio to subcutaneously receive 40 mg of either HS016 or adalimumab every other week for 24 weeks. The primary endpoint was to achieve at least a 20% improvement (ASAS20) in patients at 24 weeks according to the Assessment of Spondyloarthritis International Society criteria. The secondary endpoint included other efficacy assessment parameters, health evaluations, safety, pharmacokinetic, and immunogenicity parameters.
Following the random assignment of 648 patients into HS016 (n = 416) and adalimumab (n = 232) groups, no significant difference was found in the ASAS20 response rates at 24 weeks between the HS016 (364/416, 87.5%) and adalimumab (209/232, 90.1%) treatments and the difference between the response rates (- 2.59%; 90% confidence interval [CI] - 6.77 to 1.60) was within the predefined equivalence margin (± 15%). There were also no significant differences when the secondary endpoints were compared (all p > 0.05). Similarly, the rates of treatment-emergent adverse events (TEAEs) were not significantly different between the two groups, with most TEAEs being mild to moderate. Only nine severe cases were found, including seven within the HS016 group, three (0.7%) of which were tuberculosis cases. Plasma concentrations of HS016 and adalimumab from weeks 12 to 14 were similar during the steady-state period and steady-state maximal concentration (C) was equivalent for HS016 (7356.6 ng/mL) and adalimumab (7600.3 ng/mL). The accumulated proportion of patients with positive human anti-human antibodies (HAHAs) at week 24 was 326/412 (79.1%) in the HS016 group and 183/229 (79.9%) in the adalimumab group (p > 0.05), while the accumulated proportion of patients with positive neutralizing antibody (NAb) tests were 72/412 (17.5%) in the HS016 group and 43/229 (18.8%) in the adalimumab group (p > 0.05).
HS016 resembled adalimumab in efficacy and safety over the 24-week treatment period.
ChiCTR1900022520.
本研究旨在评估阿达木单抗生物类似药（HS016）与阿达木单抗（修美乐）治疗活动期强直性脊柱炎的疗效和安全性。
在中国 28 个中心进行了一项多中心、随机、双盲、平行、阳性对照、III 期临床试验。将活动性强直性脊柱炎患者按 2:1 的比例随机分配，皮下注射 40mg HS016 或阿达木单抗，每 2 周 1 次，共 24 周。主要终点是根据评估脊柱关节炎国际协会标准，在第 24 周时至少有 20%的患者达到缓解（ASAS20）。次要终点包括其他疗效评估参数、健康评估、安全性、药代动力学和免疫原性参数。
648 例患者随机分为 HS016（n=416）和阿达木单抗（n=232）组，第 24 周时 HS016（364/416，87.5%）和阿达木单抗（209/232，90.1%）治疗的 ASAS20 应答率无显著差异，应答率差值（-2.59%；90%置信区间[-6.77，1.60]）在预设的等效区间（±15%）内。次要终点的比较也无显著差异（均 P＞0.05）。同样，两组的治疗中出现的不良事件（TEAEs）发生率也无显著差异，大多数 TEAEs 为轻至中度。仅发现 9 例严重病例，其中 7 例发生在 HS016 组，3 例（0.7%）为结核病病例。稳态期第 12 周至第 14 周时，HS016 和阿达木单抗的血浆浓度相似，稳态时的最大浓度（C）也相当，HS016 为 7356.6ng/mL，阿达木单抗为 7600.3ng/mL。第 24 周时，HS016 组有 326/412（79.1%）例患者出现人抗人抗体（HAHAs）阳性，阿达木单抗组有 183/229（79.9%）例患者出现 HAHAs 阳性（P＞0.05）；HS016 组有 72/412（17.5%）例患者出现中和抗体（NAb）阳性，阿达木单抗组有 43/229（18.8%）例患者出现 NAb 阳性（P＞0.05）。
在 24 周的治疗期间，HS016 在疗效和安全性方面与阿达木单抗相似。
ChiCTR1900022520。
