Objectives Assess the efficacy and safety of tocilizumab in patients with systemic sclerosis (SSc) in a phase II study. Methods Patients with SSc were treated for 48 weeks in an open-label extension phase of the faSScinate study with weekly 162 mg subcutaneous tocilizumab. Exploratory end points included modified Rodnan Skin Score (mRSS) and per cent predicted forced vital capacity (%pFVC) through week 96. Results Overall, 24/44 (55%) placebo-tocilizumab and 27/43 (63%) continuous-tocilizumab patients completed week 96. Observed mean (SD (95% CI)) change from baseline in mRSS was –3.1 (6.3 (–5.4 to –0.9)) for placebo and –5.6 (9.1 (–8.9 to–2.4)) for tocilizumab at week 48 and –9.4 (5.6 (–8.9 to –2.4)) for placebo-tocilizumab and –9.1 (8.7 (–12.5 to –5.6)) for continuous-tocilizumab at week 96. Of patients who completed week 96, any decline in %pFVC was observed for 10/24 (42% (95% CI 22% to 63%)) placebo-tocilizumab and 12/26 (46% (95% CI 27% to 67%)) continuous-tocilizumab patients in the open-label period; no patients had >10% absolute decline in %pFVC. Serious infection rates/100 patient-years (95% CI) were 10.9 (3.0 to 27.9) with placebo and 34.8 (18.0 to 60.8) with tocilizumab during the double-blind period by week 48 and 19.6 (7.2 to 42.7) with placebo-tocilizumab and 0.0 (0.0 to 12.2) with continuous-tocilizumab during the open-label period. Conclusions Skin score improvement and FVC stabilisation in the double-blind period were observed in placebo-treated patients who transitioned to tocilizumab and were maintained in the open-label period. Safety data indicated increased serious infections in patients with SSc but no new safety signals with tocilizumab. Trial registration number NCT01532869; Results.

中文翻译：

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皮下托珠单抗治疗系统性硬化症的安全性和有效性：来自 II 期随机对照试验 (faSScinate) 开放标签期的结果

目标 在 II 期研究中评估托珠单抗对系统性硬化症 (SSc) 患者的疗效和安全性。方法 在 faSScinate 研究的开放标签扩展阶段，SSc 患者接受每周 162 mg 皮下注射托珠单抗治疗 48 周。探索性终点包括修正 Rodnan 皮肤评分 (mRSS) 和第 96 周预测用力肺活量百分比 (%pFVC)。 结果 总体而言，24/44 (55%) 安慰剂-托珠单抗和 27/43 (63%) 持续-托珠单抗患者完成第 96 周。观察到的 mRSS 从基线的平均变化 (SD (95% CI)) 安慰剂为 –3.1（6.3（–5.4 至 –0.9）），托珠单抗为 –5.6（9.1（–8.9 至 –2.4））在第 48 周和 –9.4（5.6（–8.9 至 –2.4））安慰剂-托珠单抗和–9.1（8.7（–12.5 至 –5.6））在第 96 周连续使用托珠单抗。在完成第 96 周的患者中，在 10/24（42%（95% CI 22% 至 63%））安慰剂-托珠单抗和 12/26（46%（95% CI 27% 至 67%））连续托珠单抗患者中观察到 %pFVC 的任何下降在开放标签期间；没有患者的 %pFVC 绝对下降超过 10%。在第 48 周的双盲期内，严重感染率/100 患者年（95% CI）安慰剂组为 10.9（3.0 至 27.9），托珠单抗组为 34.8（18.0 至 60.8），安慰剂组为 19.6（7.2 至 42.7）托珠单抗和 0.0（0.0 至 12.2）在开放标签期间使用连续托珠单抗。结论 在双盲期皮肤评分改善和 FVC 稳定在接受安慰剂治疗的患者中观察到，这些患者转换为托珠单抗并维持在开放标签期。安全性数据表明 SSc 患者严重感染增加，但托珠单抗没有新的安全性信号。试验注册号NCT01532869；结果。