Park Won, Yoo Dae Hyun, Jaworski Janusz, Brzezicki Jan, Gnylorybov Andriy, Kadinov Vladimir, Sariego Irmgadt Goecke, Abud-Mendoza Carlos, Escalante William Jose Otero, Kang Seong Wook, Andersone Daina, Blanco Francisco, Hong Seung Suh, Lee Sun Hee, Braun Jürgen
Inha University Hospital, Incheon, Republic of Korea.
Hanyang University Hospital, Seoul, Republic of Korea.
Arthritis Res Ther. 2016 Jan 20;18:25. doi: 10.1186/s13075-016-0930-4.
CT-P13 (Remsima®, Inflectra®) is a biosimilar of the infliximab reference product (RP; Remicade®) and is approved in Europe and elsewhere, mostly for the same indications as RP. The aim of this study was to compare the 54-week efficacy, immunogenicity, pharmacokinetics (PK) and safety of CT-P13 with RP in patients with ankylosing spondylitis (AS), with a focus on patient-reported outcomes (PROs).
This was a multinational, double-blind, parallel-group study in patients with active AS. Participants were randomized (1:1) to receive CT-P13 (5 mg/kg) or RP (5 mg/kg) at weeks 0, 2, 6 and then every 8 weeks up to week 54. To assess responses, standardized assessment tools were used with an intention-to-treat analysis of observed data. Anti-drug antibodies (ADAs), PK parameters, and safety outcomes were also assessed.
Of 250 randomized patients (n = 125 per group), 210 (84.0 %) completed 54 weeks of treatment, with similar completion rates between groups. At week 54, Assessment of Spondylo Arthritis international Society (ASAS)20 response, ASAS40 response and ASAS partial remission were comparable between treatment groups. Changes from baseline in PROs such as mean Bath Ankylosing Spondylitis Disease Activity Index (BASDAI; CT-P13 -3.1 versus RP -2.8), Bath Ankylosing Spondylitis Functional Index (BASFI; -2.9 versus -2.7), and Short Form Health Survey (SF-36) scores (9.26 versus 10.13 for physical component summary; 7.30 versus 6.54 for mental component summary) were similar between treatment groups. At 54 weeks, 19.5 % and 23.0 % of patients receiving CT-P13 and RP, respectively, had ADAs. All observed PK parameters of CT-P13 and RP, including maximum and minimum serum concentrations, were similar through 54 weeks. The influence of ADAs on PK was similar in the two treatment groups. Most adverse events were mild or moderate in severity. There was no notable difference between treatment groups in the incidence of adverse events, serious adverse events, infections and infusion-related reactions.
CT-P13 and RP have highly comparable efficacy (including PROs) and PK up to week 54. Over a 1-year period, CT-P13 was well tolerated and displayed a safety profile comparable to RP; no differences in immunogenicity were observed.
ClinicalTrials.gov identifier: NCT01220518 . Registered 4 October 2010.
CT-P13（Remsima®，Inflectra®）是英夫利昔单抗参比产品（RP；Remicade®）的生物类似药，已在欧洲及其他地区获批，主要用于与RP相同的适应症。本研究旨在比较CT-P13与RP在强直性脊柱炎（AS）患者中的54周疗效、免疫原性、药代动力学（PK）及安全性，重点关注患者报告结局（PROs）。
这是一项针对活动性AS患者的多中心、双盲、平行组研究。参与者按1:1随机分组，在第0、2、6周接受CT-P13（5mg/kg）或RP（5mg/kg）治疗，随后每8周一次，直至第54周。为评估反应，使用标准化评估工具对观察数据进行意向性分析。还评估了抗药抗体（ADA）、PK参数及安全性结局。
250例随机分组患者（每组n = 125例）中，210例（84.0%）完成了54周治疗，两组完成率相似。在第54周时，治疗组间脊柱关节炎国际协会（ASAS）20反应、ASAS40反应及ASAS部分缓解情况相当。治疗组间PROs自基线的变化相似，如平均巴斯强直性脊柱炎疾病活动指数（BASDAI；CT-P13为-3.1，RP为-2.8）、巴斯强直性脊柱炎功能指数（BASFI；-2.9对-2.7）及简短健康调查问卷（SF-36）评分（身体成分总结评分分别为9.26和10.13；精神成分总结评分分别为7.30和6.54）。在第54周时，接受CT-P13和RP治疗的患者中分别有19.5%和23.0%出现ADA。CT-P13和RP所有观察到的PK参数，包括最大和最小血清浓度，在54周内均相似。ADA对PK的影响在两个治疗组中相似。大多数不良事件为轻度或中度严重程度。治疗组间不良事件、严重不良事件、感染及输液相关反应的发生率无显著差异。
至第54周，CT-P13和RP具有高度可比的疗效（包括PROs）和PK。在1年期间，CT-P13耐受性良好，安全性与RP相当；未观察到免疫原性差异。
ClinicalTrials.gov标识符：NCT01220518。2010年10月4日注册。
