抗合成酶综合征相关间质性肺病中利妥昔单抗和环磷酰胺的疗效：一项观察性回顾性研究。

Rituximab and Cyclophosphamide in Antisynthetase Syndrome-related Interstitial Lung Disease: An Observational Retrospective Study.

机构信息

V. Langlois, MD, Department of Internal Medicine and infectious diseases, Jacques Monod Hospital, Le Havre, and Department of Internal Medicine & Clinical Immunology, Referral Centre for Rare Neuromuscular Diseases, Pitie Salpêtrière University Hospital, AP-HP, Paris;

A. Gillibert, MD, Department of Biostatistics, Rouen University Hospital, Rouen.

出版信息

J Rheumatol. 2020 Nov 1;47(11):1678-1686. doi: 10.3899/jrheum.190505. Epub 2020 Mar 15.

DOI:10.3899/jrheum.190505

PMID:32173654

Abstract

OBJECTIVE

Antisynthetase syndrome (AS)-related interstitial lung disease (ILD) has a poor prognosis. Intravenous cyclophosphamide (IV CYC) and rituximab (RTX) are the main treatments currently used for moderate to severe ILD. Here, we compare the efficacy of CYC followed by standard immunosuppressive treatment (IST) versus RTX in AS-related ILD.

METHODS

This observational retrospective study was conducted between 2003 and 2016 in 3 tertiary care centers. All patients with AS-related ILD and treated with CYC or RTX with at least 6 months of follow-up were included. Pulmonary progression-free survival (PFS), defined according to the American Thoracic Society guidelines, was assessed at 6 months and 2 years. All severe adverse events (AE) were recorded.

RESULTS

Sixty-two patients were included. Thirty-four patients received 2-12 monthly IV CYC pulses, followed by standard IST in 30 cases (88%). The RTX group included 28 patients. Following the initial Day 1 to Day 15 infusions, RTX was repeated every 6 months in 26 cases (93%) and 15 patients (54%) concomitantly received another IST. The median steroid dose was similar between both groups. Although RTX and CYC demonstrated similar PFS at 6 months (92% vs 85%, respectively), RTX was superior at 2 years (HR 0.263, 95% CI 0.094-0.732, = 0.011). Interestingly, lower diffusing lung capacity for carbon monoxide (DLCO) at baseline was independently predictive of poor 2-year PFS [0.965 (0.936-0.995), = 0.023]. Forced vital capacity and DLCO improved in both groups without significant differences. Serious AE were similar in both groups.

CONCLUSION

Despite similar PFS at 6 months, RTX was associated with a better 2-year PFS compared to CYC in patients with AS-related ILD.

摘要

目的

抗合成酶综合征（AS）相关间质性肺病（ILD）预后不良。目前，静脉注射环磷酰胺（IV CYC）和利妥昔单抗（RTX）是治疗中重度ILD 的主要方法。本研究比较了 CYC 序贯标准免疫抑制治疗（IST）与 RTX 治疗 AS 相关 ILD 的疗效。

方法

本研究为 2003 年至 2016 年间在 3 家三级医疗机构进行的观察性回顾性研究。纳入所有接受 CYC 或 RTX 治疗且随访时间至少 6 个月的 AS 相关 ILD 患者。根据美国胸科学会指南评估 6 个月和 2 年时的无进展生存期（PFS）。记录所有严重不良事件（AE）。

结果

共纳入 62 例患者，其中 34 例接受 2-12 个周期的 IV CYC 脉冲治疗，30 例（88%）序贯标准 IST；RTX 组 28 例，26 例（93%）在初始第 1 天至第 15 天输注后每 6 个月重复一次，15 例（54%）同时接受另一种 IST。两组的中位激素剂量相似。尽管 6 个月时 RTX 和 CYC 的 PFS 相似（分别为 92%和 85%），但 2 年时 RTX 更优（HR 0.263，95%CI 0.094-0.732， = 0.011）。有趣的是，基线时较低的一氧化碳弥散量（DLCO）独立预测 2 年 PFS 不良[0.965（0.936-0.995）， = 0.023]。两组的用力肺活量和 DLCO 均有所改善，但无显著差异。两组严重 AE 相似。