Thorne Carter, Takeuchi Tsutomu, Karpouzas George Athanasios, Sheng Shihong, Kurrasch Regina, Fei Kaiyin, Hsu Benjamin
Janssen Research & Development, LLC, Spring House, Pennsylvania, USA.
University of Toronto and Southlake Regional Health Centre, Newmarket, Ontario, Canada.
RMD Open. 2018 Nov 16;4(2):e000731. doi: 10.1136/rmdopen-2018-000731. eCollection 2018.
The phase III, multicentre, randomised, double-blind, placebo-controlled, parallel-group SIRROUND-D study evaluated long-term efficacy and safety of the interleukin (IL)-6 inhibitor, sirukumab, in patients with active rheumatoid arthritis (RA) refractory to disease-modifying antirheumatic drugs (DMARDs).
Patients were randomised 1:1:1 to sirukumab 100 mg every 2 weeks (q2w), 50 mg every 4 weeks or placebo q2w subcutaneously. Patients initially randomised to placebo were rerandomised at Weeks 18, 40 or 52 to one of the sirukumab groups until Week 104.
Of 1670 randomised patients, 1402 were included in the full analysis set and 1269 in the radiographic analysis set at Week 104. American College of Rheumatology scores, Disease Activity Score based on C-reactive protein, Clinical Disease Activity Index and clinically meaningful improvements in patient-reported outcomes were sustained at Week 104 among patients initially randomised to sirukumab. Placebo patients subsequently rerandomised to sirukumab showed clinical improvements at Week 104 that were comparable to results among patients initially randomised to sirukumab. Radiographic progression from Week 52 to Week 104 was comparable between all groups whether initially randomised to sirukumab or subsequently rerandomised to sirukumab from placebo. No new safety signals were identified in the extended exposure period compared with the initial 52 weeks of treatment.
Sirukumab treatment resulted in sustained reductions in clinical signs and symptoms and minimal progression in radiographic damage over 2 years among patients with RA refractory to DMARDs. The safety profile of sirukumab was as expected for an anti-IL-6 agent, with no new signals reported.
III期、多中心、随机、双盲、安慰剂对照、平行组SIRROUND-D研究评估了白细胞介素（IL）-6抑制剂苏金单抗对病情缓解抗风湿药物（DMARDs）治疗无效的活动性类风湿关节炎（RA）患者的长期疗效和安全性。
患者按1:1:1随机分组，分别接受每2周皮下注射100mg苏金单抗、每4周皮下注射50mg苏金单抗或每2周皮下注射安慰剂。最初随机分配至安慰剂组的患者在第18周、40周或52周重新随机分配至苏金单抗组之一，直至第104周。
在1670例随机分组的患者中，1402例纳入全分析集，1269例纳入第104周的影像学分析集。最初随机分配至苏金单抗组的患者在第104周时，美国风湿病学会评分、基于C反应蛋白的疾病活动评分、临床疾病活动指数以及患者报告结局方面具有临床意义的改善得以维持。随后重新随机分配至苏金单抗组的安慰剂组患者在第104周时显示出临床改善，与最初随机分配至苏金单抗组的患者结果相当。无论最初随机分配至苏金单抗组还是随后从安慰剂组重新随机分配至苏金单抗组，所有组从第52周至第104周的影像学进展相当。与最初52周的治疗相比，在延长暴露期未发现新的安全信号。
对于DMARDs治疗无效的RA患者，苏金单抗治疗在2年内可使临床体征和症状持续减轻，影像学损伤进展最小。苏金单抗的安全性与抗IL-6药物预期一致，未报告新的信号。
