Objectives

To evaluate the efficacy and safety of ultra-low dose (100 mg) rituximab (RTX) administration in anti-melanoma differentiation-associated gene 5 (MDA5) positive patients with polymyositis/dermatomyositis (PM/DM) associated interstitial lung disease.

Methods

This retrospective study included anti-MDA5 antibody positive ILD subjects in the First Affiliated Hospital of Guangzhou Medical University from November 2017 to March 2019. Independent predictors for 180-day mortality were measured by Cox regression analysis. Patients were divided into 3 groups: Group 1 (non-cyclophosphamide (CTX)/RTX) (n = 10), Group 2 (CTX only) (n = 19) and Group 3 (RTX with/without CTX) (n = 11). The 180-day mortality was compared among 3 groups with Kaplan-Meier analysis. Post-RTX serological parameters as well as adverse events were evaluated.

Results

Forty patients were included with the mean age of 51.3 years. Elevated IL-10 level and CD4⁺/8⁺ ratio were considered as risk factors of 180-day mortality. Kaplan-Meier analysis showed a trend toward decrease, albeit non-significant, in 180-day mortality in Group 3 (P = 0.26). The administration of 100 mg RTX brought down B cell within 7 days that lasted for 180 days. There were 7 and 6 infection events observed within 2 months of CTX/RTX treatment in Group 2 and 3, with 5 and 2 fatal cases respectively. Cytomegalovirus infection accounted for half infection events in Group 3.

Conclusion

We found a pronounced and prolonged B cell depletion following 100 mg RTX infusion and RTX add-on may be effective in anti-MDA5 positive ILD patients. However, infection, especially opportunistic infection, should be concerned during the treatment.

中文翻译：

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抗MDA5阳性多发性肌炎/皮肌炎相关ILD的超低剂量利妥昔单抗作为附加治疗

目标

为了评估超低剂量（100 mg）利妥昔单抗（RTX）在多发性肌炎/皮肌炎（PM / DM）相关性间质性肺疾病的抗黑素瘤分化相关基因5（MDA5）阳性患者中的疗效和安全性。

方法

这项回顾性研究纳入了2017年11月至2019年3月在广州医科大学附属第一医院抗MDA5抗体阳性的ILD受试者。通过Cox回归分析测量180天死亡率的独立预测因子。患者分为3组：第1组（非环磷酰胺（CTX）/ RTX）（n = 10），第2组（仅CTX）（n = 19）和第3组（有/无CTX的RTX）（n = 11） ）。通过Kaplan-Meier分析比较了3组的180天死亡率。评估了RTX后的血清学参数以及不良事件。

结果

纳入40例患者，平均年龄为51.3岁。IL-10水平和CD4 ⁺ / 8 ⁺比率升高被认为是180天死亡率的危险因素。Kaplan-Meier分析显示第3组180天死亡率有下降趋势，尽管无统计学意义（P  = 0.26）。100 mg RTX的给药在7天之内使B细胞持续了180天。第2组和第3组在接受CTX / RTX治疗的2个月内观察到7和6个感染事件，分别有5和2个致命病例。巨细胞病毒感染占第3组感染事件的一半。

结论

我们发现，在抗MDA5阳性的ILD患者中，接受100 mg RTX输注和添加RTX后，B细胞的耗竭会持续很长时间。但是，在治疗期间应注意感染，尤其是机会性感染。