ZS Associates, Global Health Economics and Outcomes Research, New York, New York.
Division of Epidemiology and.
Ann Am Thorac Soc. 2024 Feb;21(2):328-337. doi: 10.1513/AnnalsATS.202301-056OC.
The American Thoracic Society (ATS) convened an international, multidisciplinary panel to develop clinical practice guidelines for the treatment of systemic sclerosis-associated interstitial lung disease (SSc-ILD). To conduct a systematic review and evaluate the literature to determine the impact of treating patients with SSc-ILD with tocilizumab on prespecified critical and important outcomes determined by the ATS guideline panel. A literature search was conducted across MEDLINE, EMBASE, and Cochrane databases through June 2022 for studies using tocilizumab to treat patients with SSc-ILD. Mortality and disease progression were determined to be critical outcomes of focus, with quality of life and adverse events important outcomes. Data on these outcomes were extracted and meta-analyses performed using the generic inverse variance method when possible. The Grading of Recommendations, Assessment, Development, and Evaluation Working Group method was used to assess the quality of evidence. The literature review resulted in five studies for inclusion. The absolute decrease from baseline in forced vital capacity (FVC) for the tocilizumab arm was 118 ml, 241 ml, and 129 ml less than the placebo arm at 24, 48, and 96 weeks, respectively, favoring tocilizumab. The mean decrease in FVC% predicted at 48 weeks was 6.50% less and the risk of decrease >10% was 66% less in the tocilizumab arm, whereas patients were 1.97 times more likely to have any increase in FVC% predicted if they received tocilizumab in place of placebo. When the placebo arm was given tocilizumab from 48 to 96 weeks, the mean change in absolute FVC was 54.90 ml less and the mean change in FVC% predicted was 1.30% less. For diffusing capacity of the lung for carbon monoxide (Dl)% predicted, at 48 weeks there was 1.50% less change and from 48 to 96 weeks there was 5.40% less change in the tocilizumab arm. Quantitative Interstitial Lung Disease scores and Quantitative Lung Fibrosis scores at 48 weeks and modified Rodnan skin scores at 72 weeks all favored the tocilizumab arm, as did several adverse event parameters, including serious adverse events (mean difference, -27.40; 95% confidence interval, -30.10 to -24.70). The quality of evidence was very low grade. Tocilizumab use in patients with SSc-ILD is associated with less disease progression and a better toxicity profile than placebo. However, the quality of evidence is very low, and large prospective studies dedicated to assessing tocilizumab specifically for SSc-ILD are needed.
美国胸科学会（ATS）召集了一个国际、多学科小组，制定了治疗系统性硬化症相关间质性肺病（SSc-ILD）的临床实践指南。为了进行系统评价并评估文献，以确定使用托珠单抗治疗 SSc-ILD 患者对 ATS 指南小组确定的关键和重要结局的影响。通过 MEDLINE、EMBASE 和 Cochrane 数据库对截至 2022 年 6 月使用托珠单抗治疗 SSc-ILD 患者的研究进行了文献检索。死亡率和疾病进展被确定为重点关注的关键结局，生活质量和不良事件为重要结局。当可能时，使用通用逆方差法提取这些结局的数据并进行荟萃分析。使用推荐评估、制定和评估工作组（Grading of Recommendations, Assessment, Development, and Evaluation Working Group）方法评估证据质量。文献复习共纳入了五项研究。托珠单抗组在 24、48 和 96 周时，用力肺活量（FVC）从基线的绝对下降分别比安慰剂组少 118ml、241ml 和 129ml，这表明托珠单抗具有优势。48 周时 FVC%预计的平均下降少 6.50%，托珠单抗组下降>10%的风险低 66%，而如果患者接受托珠单抗而不是安慰剂，FVC%预计增加的可能性高 1.97 倍。当安慰剂组在 48 至 96 周时给予托珠单抗时，绝对 FVC 的平均变化少 54.90ml，FVC%预计的平均变化少 1.30%。对于一氧化碳弥散量（Dl）%预计，48 周时变化少 1.50%，48 至 96 周时变化少 5.40%。48 周时定量间质性肺病评分和定量肺纤维化评分以及 72 周时改良罗德纳皮肤评分均有利于托珠单抗组，几个不良事件参数也有利于托珠单抗组，包括严重不良事件（平均差值，-27.40；95%置信区间，-30.10 至-24.70）。证据质量为极低等级。托珠单抗在 SSc-ILD 患者中的使用与安慰剂相比，疾病进展较少，毒性谱更好。然而，证据质量非常低，需要专门针对 SSc-ILD 评估托珠单抗的大型前瞻性研究。
