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吸入莫拉司亭治疗自身免疫性肺泡蛋白沉着症疗效显著
作者:小柯机器人 发布时间:2020/9/12 21:42:11

美国辛辛那提儿童医院医疗中心Bruce C. Trapnell团队研究了吸入莫拉司亭治疗自身免疫性肺泡蛋白沉着症的疗效。2020年9月7日,《新英格兰医学杂志》在线发表了该成果。

自身免疫性肺泡蛋白沉着症(aPAP)是一种罕见疾病,其特点是进行性表面活性物质积累和低氧血症。aPAP由粒细胞-巨噬细胞集落刺激因子(GM-CSF)信号中断引起,肺泡巨噬细胞需要它来清除表面活性剂。近期研究表明,吸入GM-CSF可改善aPAP患者的动脉血氧分压。

在一项双盲、安慰剂对照、三组试验中,研究组招募了138名aPAP患者,将其随机分组,其中46名连续吸入重组GM-CSF莫拉司亭,45名每隔一周吸入,47名接受安慰剂治疗,连续治疗24周。主要终点为24周时肺泡-动脉氧浓度(A-aDO2)较基线的变化。

4例患者(莫拉司亭组各1例,安慰剂组2例)在动脉血气测量期间接受鼻氧治疗。连续吸入莫拉司亭的患者24周时A-aDO2较基线的改善程度显著优于安慰剂组,包括24周时圣乔治呼吸问卷总分在内的其他指标较基线的改善程度亦均显著优于安慰剂组。莫拉司亭连续治疗的多个终点的疗效均显著优于间歇治疗。除莫拉司亭连续治疗组中胸痛发生率较高之外,三组患者的不良事件和严重不良事件的发生率相差不大。

总之,对于aPAP患者,每日吸入莫拉司亭与安慰剂相比,可有效改善肺气体转移和功能健康状况,且不良事件未增加。

附:英文原文

Title: Inhaled Molgramostim Therapy in Autoimmune Pulmonary Alveolar Proteinosis

Author: Bruce C. Trapnell, M.D.,, Yoshikazu Inoue, M.D., Ph.D.,, Francesco Bonella, M.D., Ph.D.,, Cliff Morgan, B.M.,, Stéphane Jouneau, M.D., Ph.D.,, Elisabeth Bendstrup, M.D., Ph.D.,, Ilaria Campo, Ph.D.,, Spyros A. Papiris, M.D.,, Etsuro Yamaguchi, M.D., Ph.D.,, Erdogan Cetinkaya, M.D.,, Mikhail M. Ilkovich, M.D.,, Mordechai R. Kramer, M.D.,, Marcel Veltkamp, M.D.,, Michael Kreuter, M.D.,, Tomohisa Baba, M.D.,, Cecilia Ganslandt, M.D.,, Inge Tarnow, D.V.M., Ph.D.,, Grant Waterer, M.B., B.S., Ph.D., M.B.A.,, and Taneli Jouhikainen, M.D., Ph.D., M.B.A.

Issue&Volume: 2020-09-07

Abstract:

Background

Autoimmune pulmonary alveolar proteinosis (aPAP) is a rare disease characterized by progressive surfactant accumulation and hypoxemia. It is caused by disruption of granulocyte–macrophage colony-stimulating factor (GM-CSF) signaling, which pulmonary alveolar macrophages require to clear surfactant. Recently, inhaled GM-CSF was shown to improve the partial pressure of arterial oxygen in patients with aPAP.

Methods

In a double-blind, placebo-controlled, three-group trial, we randomly assigned patients with aPAP to receive the recombinant GM-CSF molgramostim (300 μg once daily by inhalation), either continuously or intermittently (every other week), or matching placebo. The 24-week intervention period was followed by an open-label treatment-extension period. The primary end point was the change from baseline in the alveolar–arterial difference in oxygen concentration (A-aDo2) at week 24.

Results

In total, 138 patients underwent randomization; 46 were assigned to receive continuous molgramostim, 45 to receive intermittent molgramostim, and 47 to receive placebo. Invalid A-aDo2 data for 4 patients (1 in each molgramostim group and 2 in the placebo group) who received nasal oxygen therapy during arterial blood gas measurement were replaced by means of imputation. For the primary end point — the change from baseline in the A-aDo2 at week 24 — improvement was greater among patients receiving continuous molgramostim than among those receiving placebo (12.8 mm Hg vs. 6.6 mm Hg; estimated treatment difference, 6.2 mm Hg; P=0.03 by comparison of least-squares means). Patients receiving continuous molgramostim also had greater improvement than those receiving placebo for secondary end points, including the change from baseline in the St. George’s Respiratory Questionnaire total score at week 24 (12.4 points vs. 5.1 points; estimated treatment difference, 7.4 points; P=0.01 by comparison of least-squares means). For multiple end points, improvement was greater with continuous molgramostim than with intermittent molgramostim. The percentages of patients with adverse events and serious adverse events were similar in the three groups, except for the percentage of patients with chest pain, which was higher in the continuous-molgramostim group.

Conclusions

In patients with aPAP, daily administration of inhaled molgramostim resulted in greater improvements in pulmonary gas transfer and functional health status than placebo, with similar rates of adverse events.

DOI: 10.1056/NEJMoa1913590

Source: https://www.nejm.org/doi/full/10.1056/NEJMoa1913590

 

期刊信息

The New England Journal of Medicine:《新英格兰医学杂志》,创刊于1812年。隶属于美国麻省医学协会,最新IF:70.67
官方网址:http://www.nejm.org/
投稿链接:http://www.nejm.org/page/author-center/home