Khanna Dinesh, Lin Celia J F, Furst Daniel E, Wagner Bridget, Zucchetto Mauro, Raghu Ganesh, Martinez Fernando J, Goldin Jonathan, Siegel Jeffrey, Denton Christopher P
Department of Internal Medicine, University of Michigan, Ann Arbor, Michigan.
Genentech, South San Francisco, California.
Am J Respir Crit Care Med. 2022 Mar 15;205(6):674-684. doi: 10.1164/rccm.202103-0714OC.
Tocilizumab, an anti-IL-6 receptor antibody, had no statistically significant effect on skin sclerosis but preserved lung function over 48 weeks in patients with early systemic sclerosis (SSc)-associated interstitial lung disease (ILD) in a phase 3 randomized controlled trial. Assess long-term safety and efficacy of tocilizumab. Adults with diffuse cutaneous SSc for ⩽60 months and elevated acute-phase reactants, including those with ILD, received weekly placebo or tocilizumab 162 mg subcutaneously in the 48-week, double-blind period and then open-label tocilizumab from Weeks 48 to 96 (placebo-tocilizumab; continuous-tocilizumab). Eighty-two of 107 patients in the placebo-tocilizumab group and 85 of 105 patients in the continuous-tocilizumab group completed 96 weeks. Mean age and disease duration were 48 years and 23 months; high-resolution computed tomography revealed ILD in 61%. Mean (95% confidence interval [CI]) change in modified Rodnan skin score from baseline to week 96 was -8.4 (-10.0 to -6.8) for placebo-tocilizumab and -9.6 (-10.9 to -8.4) for continuous-tocilizumab. Mean (95% CI) change in FVC (percent predicted) from baseline to week 96 was -3.3 (-5.1 to -1.5) for placebo-tocilizumab and -0.5 (-2.4 to 1.3) for continuous-tocilizumab among completers and, in a analysis, -4.1 (-6.7 to -1.6) and -0.6 (-3.1 to 2.0), respectively, among completers with ILD (mean [95% CI] change from Weeks 48 to 96: 0.9 [-0.8 to 2.7] and -0.4 [-2.3 to 1.5], respectively). Rates per 100 patient-years of serious adverse events from Weeks 48 to 96 were 14.8 for placebo-tocilizumab and 15.8 for continuous-tocilizumab. Tocilizumab preserved lung function, slowing decline in FVC, in patients with SSc, including those with ILD. Long-term safety was consistent with the known safety profile of tocilizumab. Clinical trial registered with www.clinicaltrials.gov (NCT02453256).
托珠单抗是一种抗白细胞介素-6受体抗体，在一项3期随机对照试验中，对于早期系统性硬化症（SSc）相关间质性肺疾病（ILD）患者，它对皮肤硬化无统计学显著影响，但在48周内可维持肺功能。评估托珠单抗的长期安全性和疗效。患有弥漫性皮肤型SSc且病程≤60个月、急性期反应物升高的成年人，包括患有ILD的患者，在48周的双盲期接受每周一次的安慰剂或皮下注射162 mg托珠单抗，然后在第48周至96周接受开放标签的托珠单抗治疗（安慰剂-托珠单抗组；持续-托珠单抗组）。安慰剂-托珠单抗组107例患者中的82例和持续-托珠单抗组105例患者中的85例完成了96周治疗。平均年龄和病程分别为48岁和23个月；高分辨率计算机断层扫描显示61%的患者有ILD。从基线到第96周，安慰剂-托珠单抗组改良Rodnan皮肤评分的平均（95%置信区间[CI]）变化为-8.4（-10.0至-6.8），持续-托珠单抗组为-9.6（-10.9至-8.4）。在完成治疗的患者中，从基线到第96周，安慰剂-托珠单抗组用力肺活量（预测值百分比）的平均（95%CI）变化为-3.3（-5.1至-1.5），持续-托珠单抗组为-0.5（-2.4至1.3）；在有ILD的完成治疗的患者中，分析显示分别为-4.1（-6.7至-1.6）和-0.6（-3.1至2.0）（从第48周到96周的平均[95%CI]变化分别为0.9[-0.8至2.7]和-0.4[-2.3至1.5]）。从第48周到96周，每100患者年严重不良事件发生率，安慰剂-托珠单抗组为14.8，持续-托珠单抗组为15.8。托珠单抗可维持SSc患者（包括患有ILD的患者）的肺功能，减缓用力肺活量下降。长期安全性与托珠单抗已知的安全性特征一致。临床试验已在www.clinicaltrials.gov注册（NCT02453256）。
