INTRODUCTION The effectiveness of CD20 targeting in connective tissue diseases (CTD) with lung involvement is controversial. This paper aims to review the current evidence about rituximab (RTX) use in CTD-related interstitial lung disease (ILD). METHODS We performed a systematic review of papers published between January 2009 and May 2019. We included clinical trials, case/control studies and cohort studies. We excluded letters, case reports, case series, reviews, and full articles when not in English. The selected studies listed as primary or secondary outcome a variation in pulmonary function tests or in the scores used to radiologically stage lung involvement, in CTD-related ILD patients after RTX. RESULTS Out of 1206 potentially eligible articles, 24 papers were selected: 3 retrospectively described cohorts of patients with different CTD, 14 dealt with systemic sclerosis (SSc)-related ILD, 5 with idiopathic inflammatory myopathies (IIMs)-related ILD, and 2 with Sjögren's Syndrome-related ILD. A direct comparison of the selected studies was hampered by their heterogeneity for outcomes, follow-up duration, the severity of lung involvement, and clinical features of study populations. However, an overall agreement existed concerning the effectiveness of RTX in the stabilization of lung disease, with some studies reporting an improvement of functional parameters from baseline. IIM-related ILD appeared more responsive than other CTD-related ILD to CD20 targeting. CONCLUSION RTX is a promising therapeutic tool in CTD-related ILD. This systematic review remarks the unmet need of multicenter prospective studies aiming to evaluate the effectiveness of RTX with adequate sample size and study design.

中文翻译：

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靶向CD20治疗与结缔组织疾病相关的间质性肺疾病：系统综述。

引言CD20靶向治疗伴有肺部侵袭的结缔组织疾病（CTD）的有效性是有争议的。本文旨在综述有关在CTD相关性间质性肺病（ILD）中使用利妥昔单抗（RTX）的最新证据。方法我们对2009年1月至2019年5月之间发表的论文进行了系统的综述。我们包括临床试验，病例/对照研究和队列研究。如果不是英文，我们排除了信件，案例报告，案例系列，评论和全文。选定的研究在RTX后与CTD相关的ILD患者中，肺功能检查或放射学分期的肺部评分的变化列为主要或次要结果。结果从1206篇可能符合条件的文章中，选择了24篇文章：3例回顾性描述的不同CTD患者的队列，14例与系统性硬化症（SSc）相关的ILD，5例与特发性炎症性肌病（IIMs）相关的ILD，2例与干燥综合征相关的ILD。所选研究的直接比较因其结果，随访时间，肺部受累的严重程度以及研究人群的临床特征的异质性而受到阻碍。但是，关于RTX在稳定肺部疾病方面的有效性存在总体共识，一些研究报告称其功能参数较基线有所改善。IIM相关的ILD对CD20靶向的反应似乎比其他CTD相关的ILD更为敏感。结论RTX是与CTD相关的ILD的有前途的治疗工具。