Emery Paul, Vencovský Jiří, Sylwestrzak Anna, Leszczyński Piotr, Porawska Wieslawa, Stasiuk Barbara, Hilt Joanna, Mosterova Zdenka, Cheong Soo Yeon, Ghil Jeehoon
Arthritis Research, Leeds Institute of Rheumatic and Musculoskeletal Medicine, University of Leeds, Leeds, UK.
NIHR Leeds Musculoskeletal Biomedical Research Unit, Leeds Teaching Hospitals NHS Trust, Leeds, UK.
Ann Rheum Dis. 2017 Nov 13;76(12):1986-1991. doi: 10.1136/annrheumdis-2017-211591.
SB4 (Benepali, Brenzys) is a biosimilar of reference etanercept (ETN). In a randomised, double-blind, 52-week study, SB4 demonstrated comparable efficacy and safety to ETN in patients with rheumatoid arthritis (RA). The open-label extension period evaluated long-term efficacy, safety and immunogenicity when continuing SB4 versus switching from ETN to SB4.
In the randomised, double-blind phase, patients received weekly subcutaneous administration of 50 mg SB4 or ETN with background methotrexate for up to 52 weeks. Patients in the Czech Republic and Poland who completed the 52-week visit were enrolled in the open-label extension period and received SB4 for 48 additional weeks. Efficacy, safety and immunogenicity were assessed up to week 100.
Of 245 patients entering the extension period, 126 continued to receive SB4 (SB4/SB4) and 119 switched to SB4 (ETN/SB4). American College of Rheumatology (ACR) response rates were sustained and comparable between SB4/SB4 and ETN/SB4 with ACR20 response rates at week 100 of 77.9% and 79.1%, respectively. Other efficacy results, including radiographic progression, were also comparable between the groups. After week 52, rates of treatment-emergent adverse events were 47.6% (SB4/SB4) and 48.7% (ETN/SB4); one patient/group developed non-neutralising antidrug antibodies. No cases of active tuberculosis or injection-site reactions were reported during the extension period. One patient (SB4/SB4) died of hepatic cancer.
SB4 was effective and well tolerated over 2 years in patients with RA. Efficacy, safety and immunogenicity were comparable between the SB4/SB4 and ETN/SB4 groups, showing no risk associated with switching patients from ETN to SB4.
NCT01895309; 2012-005026-30.
SB4（Benepali、Brenzys）是参比依那西普（ETN）的生物类似药。在一项随机、双盲、为期52周的研究中，SB4在类风湿关节炎（RA）患者中显示出与ETN相当的疗效和安全性。开放标签延长期评估了持续使用SB4与从ETN转换为SB4时的长期疗效、安全性和免疫原性。
在随机、双盲阶段，患者每周皮下注射50mg SB4或ETN，并联合背景甲氨蝶呤，持续长达52周。在捷克共和国和波兰完成52周访视的患者进入开放标签延长期，再接受48周的SB4治疗。评估至第100周时的疗效、安全性和免疫原性。
进入延长期的245例患者中，126例继续接受SB4治疗（SB4/SB4组），119例转换为SB4治疗（ETN/SB4组）。美国风湿病学会（ACR）反应率得以维持，SB4/SB4组和ETN/SB4组相当，第100周时ACR20反应率分别为77.9%和79.1%。其他疗效结果，包括影像学进展，在两组间也相当。52周后，治疗中出现的不良事件发生率在SB4/SB4组为47.6%，在ETN/SB4组为48.7%；每组各有1例患者产生非中和性抗药抗体。延长期内未报告活动性结核或注射部位反应病例。1例患者（SB4/SB4组）死于肝癌。
SB4在RA患者中2年的治疗效果良好且耐受性佳。SB4/SB4组和ETN/SB4组在疗效、安全性和免疫原性方面相当，表明将患者从ETN转换为SB4无风险。
NCT01895309；2012-005026-30。
