Table1_Rituximab for the treatment of connective tissue disease–associated interstitial lung disease: A systematic review and meta-analysis.docx

Background: Interstitial lung disease (ILD) is a common pulmonary disease often associated with significant morbidity and mortality in patients with connective tissue diseases (CTD). Currently, no gold-standard therapies are available for CTD-ILD. Recently, several studies have proposed that rituximab (RTX) may be effective for the treatment of CTD-ILD.
Objectives: This study aimed to systematically evaluate the efficacy and safety of RTX for the treatment of CTD-ILD.
Methods: Studies were selected from PubMed, Embase, and Cochrane Library, up to 20 July 2022. Improvement and stable rates were extracted as the main outcomes and pooled using the weighted mean proportion with fixed or random-effects models, in case of significant heterogeneity (I2 > 50%). Safety analysis was performed based on the adverse events reported in all of the studies.
Results: Thirteen studies (312 patients) were included in the meta-analysis. The follow-up durations ranged from 6 to 36 months. The pooled improvement rate was 35.0% (95% CI: 0.277–0.442), while the pooled stable rate was 59.2% (95% CI: 0.534–0.656). Anti-synthetase syndrome associated with ILD [ASS-ILD, 48.1% (95% CI, 0.373–0.620)] and idiopathic inflammatory myopathies associated with ILD [IIM-ILD, non-ASS, 47.4% (95% CI, 0.266–0.846)] had higher improvement rates than the other types. A total of 106 adverse events associated with RTX or progressive ILD were reported among the 318 patients, 55.7% of which were mild. Among 19 deaths, 17 were due to ILD progression, one to severe pulmonary arterial hypertension, and one to Pneumocystis jirovecii infection.
Conclusion: RTX, which exhibits a satisfactory safety profile, is an effective treatment option for CTD-ILD, even in patients who fail to respond to other therapies. Further randomized trials are needed to assess the efficacy of rituximab compared to other treatments for CTD-ILD.
Systematic review registration: PROSPERO, identifier (CRD42022363403).

背景：间质性肺疾病（interstitial lung disease, ILD）是一类常见的肺部疾病，常与结缔组织病（connective tissue diseases, CTD）患者出现较高的发病率与死亡率相关。目前，针对CTD相关ILD（CTD-ILD）尚无金标准治疗方案。近期多项研究表明，利妥昔单抗（rituximab, RTX）或可有效治疗CTD-ILD。
目的：本研究旨在系统评价利妥昔单抗用于CTD-ILD治疗的有效性与安全性。
方法：检索截至2022年7月20日的PubMed、Embase及Cochrane Library数据库收录的相关研究。提取病情改善率与病情稳定率作为主要结局指标，采用加权平均比例法进行合并分析，当存在显著异质性（I²>50%）时采用随机效应模型，否则采用固定效应模型。安全性分析基于所有纳入研究中报告的不良事件展开。
结果：本荟萃分析（meta-analysis）共纳入13项研究，共计312例患者。随访时长介于6至36个月之间。合并后的病情改善率为35.0%（95%置信区间：confidence interval, CI 0.277~0.442），病情稳定率为59.2%（95%置信区间：0.534~0.656）。伴间质性肺疾病的抗合成酶综合征（anti-synthetase syndrome associated with ILD, ASS-ILD，48.1%，95%置信区间：0.373~0.620）与伴间质性肺疾病的特发性炎性肌病（idiopathic inflammatory myopathies associated with ILD, IIM-ILD，非ASS亚型，47.4%，95%置信区间：0.266~0.846）的病情改善率高于其他亚型。共318例患者中报告了106例与利妥昔单抗或ILD进展相关的不良事件，其中55.7%为轻度不良事件。19例死亡病例中，17例因ILD进展所致，1例因重度肺动脉高压，1例因耶氏肺孢子菌（Pneumocystis jirovecii）感染。
结论：利妥昔单抗安全性良好，可作为CTD-ILD的有效治疗选择，即便对于其他治疗方案应答不佳的患者亦适用。未来仍需开展随机对照试验，以对比利妥昔单抗与其他疗法用于CTD-ILD的疗效。
系统评价注册：PROSPERO，注册号（CRD42022363403）。