双盲试验54周后生物类似药SB2与参比英夫利昔单抗的对比：临床、结构及安全性结果
Comparing biosimilar SB2 with reference infliximab after 54 weeks of a double-blind trial: clinical, structural and safety results.
作者信息
Smolen Josef S, Choe Jung-Yoon, Prodanovic Nenad, Niebrzydowski Jaroslaw, Staykov Ivan, Dokoupilova Eva, Baranauskaite Asta, Yatsyshyn Roman, Mekic Mevludin, Porawska Wieskawa, Ciferska Hana, Jedrychowicz-Rosiak Krystyna, Zielinska Agnieszka, Choi Jasmine, Rho Young Hee
机构信息
Division of Rheumatology, Department of Medicine, Medical University of Vienna, Vienna, Austria.
Division of Rheumatology, Daegu Catholic University Medical Center, Daegu, South Korea.
出版信息
Rheumatology (Oxford). 2017 Oct 1;56(10):1771-1779. doi: 10.1093/rheumatology/kex254.
OBJECTIVES
SB2 is a biosimilar to the reference infliximab (INF). Similar efficacy, safety and immunogenicity between SB2 and INF up to 30 weeks were previously reported. This report investigates such clinical similarity up to 54 weeks, including structural joint damage.
METHODS
In this phase III, double-blind, parallel-group, multicentre study, patients with moderate to severe RA despite MTX were randomized (1:1) to receive 3 mg/kg of either SB2 or INF at 0, 2, 6 and every 8 weeks thereafter. Dose escalation by 1.5 mg/kg up to a maximum dose of 7.5 mg/kg was allowed after week 30. Efficacy, safety and immunogenicity were measured at each visit up to week 54. Radiographic damage evaluated by modified total Sharp score was measured at baseline and week 54.
RESULTS
A total of 584 patients were randomized to receive SB2 (n = 291) or INF (n = 293). The rate of radiographic progression was comparable between SB2 and INF (mean modified total Sharp score difference: SB2, 0.38; INF, 0.37) at 1 year. ACR responses, 28-joint DAS, Clinical Disease Activity Index and Simplified Disease Activity Index were comparable between SB2 and INF up to week 54. The incidence of treatment-emergent adverse events and anti-drug antibodies were comparable between treatment groups. Such comparable trends of efficacy, safety and immunogenicity were consistent from baseline up to 54 weeks. The pattern of dose increment was also comparable between SB2 and INF.
CONCLUSION
SB2 maintained similar efficacy, safety and immunogenicity with INF up to 54 weeks in patients with moderate to severe RA. Radiographic progression was comparable at 1 year.
TRIAL REGISTRATION
ClinicalTrials.gov (http://clinicaltrials.gov; NCT01936181) and EudraCT (https://www.clinicaltrialsregister.eu; 2012-005733-37).
目的
SB2是英夫利昔单抗（INF）的生物类似药。此前报道了SB2与INF在长达30周内具有相似的疗效、安全性和免疫原性。本报告调查了长达54周的临床相似性，包括结构性关节损伤。
方法
在这项III期、双盲、平行组、多中心研究中，尽管使用了甲氨蝶呤（MTX）但仍患有中度至重度类风湿性关节炎（RA）的患者被随机分组（1:1），在第0、2、6周及之后每8周接受3mg/kg的SB2或INF治疗。在第30周后允许以1.5mg/kg的剂量递增，直至最大剂量7.5mg/kg。在直至第54周的每次访视时测量疗效、安全性和免疫原性。在基线和第54周时通过改良总Sharp评分评估放射学损伤。
结果
共有584例患者被随机分组接受SB2（n = 291）或INF（n = 293）治疗。在1年时，SB2和INF之间的放射学进展率相当（平均改良总Sharp评分差异：SB2为0.38；INF为0.37）。直至第54周，SB2和INF之间的美国风湿病学会（ACR）反应、28关节疾病活动评分（DAS）、临床疾病活动指数（CDAI）和简化疾病活动指数（SDAI）相当。治疗中出现的不良事件和抗药物抗体的发生率在治疗组之间相当。从基线到54周，疗效、安全性和免疫原性的这种可比趋势是一致的。SB2和INF之间的剂量增加模式也相当。
结论
在中度至重度RA患者中，SB2在长达54周内与INF保持相似的疗效、安全性和免疫原性。1年时的放射学进展相当。
试验注册
ClinicalTrials.gov（http://clinicaltrials.gov；NCT01936181）和欧洲临床试验数据库（EudraCT）（https://www.clinicaltrialsregister.eu；2012-005733-37）。
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