小柯机器人

意大利天主教圣心大学Luca Richeldi团队研究了首选磷酸二酯酶4B抑制剂治疗特发性肺纤维化的疗效。该研究于2022年5月15日发表于《新英格兰医学杂志》。

磷酸二酯酶4（PDE4）抑制剂与抗炎和抗纤维化作用相关，这可能对特发性肺纤维化患者有益。

在这项临床2期、双盲、安慰剂对照试验中，研究组探讨了口服PDE4B亚型优先抑制剂BI 1015550对特发性肺纤维化患者的疗效和安全性。将患者按2:1的比例随机分配，分别接受BI 1015550（剂量为18 mg，每日两次）或安慰剂治疗。主要终点是12周时用力肺活量（FVC）从基线检查时的变化，根据不使用或使用抗纤维化药物的背景分别采用贝叶斯方法进行分析。

共有147名患者被随机分配接受BI 1015550或安慰剂治疗。在没有抗纤维化药物使用背景的患者中，BI 1015550组FVC中位增加了5.7 ml，安慰剂组FVC中位减少81.7 ml，中位数差异88.4 ml，组间差异显著。在有使用抗纤维化药物背景的患者中，BI 1015550组FVC中位增加了2.7 ml，安慰剂组FVC中位减少59.2 ml，中位数差异62.4 ml，组间差异亦显著。

重复测量分析的混合模型提供了与贝叶斯分析一致的结果。最常见的不良事件是腹泻。共有13名患者因不良事件停止BI 1015550的治疗。两个试验组出现严重不良事件或极其严重不良事件的患者比例相似。

研究结果表明，在这项安慰剂对照试验中，BI 1015550单独治疗或联合使用抗纤维化药物，可防止特发性肺纤维化患者肺功能下降。

附：英文原文

Title: Trial of a Preferential Phosphodiesterase 4B Inhibitor for Idiopathic Pulmonary Fibrosis | NEJM

Author: Luca Richeldi, M.D., Ph.D.,, Arata Azuma, M.D., Ph.D.,, Vincent Cottin, M.D., Ph.D.,, Christian Hesslinger, Ph.D.,, Susanne Stowasser, M.D.,, Claudia Valenzuela, M.D.,, Marlies S. Wijsenbeek, M.D., Ph.D.,, Donald F. Zoz, M.D.,, Florian Voss, Ph.D.,, and Toby M. Maher, M.D., Ph.D.

Issue&Volume: 2022-05-15

Abstract:

Background

Phosphodiesterase 4 (PDE4) inhibition is associated with antiinflammatory and antifibrotic effects that may be beneficial in patients with idiopathic pulmonary fibrosis.

Methods

In this phase 2, double-blind, placebo-controlled trial, we investigated the efficacy and safety of BI 1015550, an oral preferential inhibitor of the PDE4B subtype, in patients with idiopathic pulmonary fibrosis. Patients were randomly assigned in a 2:1 ratio to receive BI 1015550 at a dose of 18 mg twice daily or placebo. The primary end point was the change from baseline in the forced vital capacity (FVC) at 12 weeks, which we analyzed with a Bayesian approach separately according to background nonuse or use of an antifibrotic agent.

Results

A total of 147 patients were randomly assigned to receive BI 1015550 or placebo. Among patients without background antifibrotic use, the median change in the FVC was 5.7 ml (95% credible interval, –39.1 to 50.5) in the BI 1015550 group and –81.7 ml (95% credible interval, –133.5 to –44.8) in the placebo group (median difference, 88.4 ml; 95% credible interval, 29.5 to 154.2; probability that BI 1015550 was superior to placebo, 0.998). Among patients with background antifibrotic use, the median change in the FVC was 2.7 ml (95% credible interval, –32.8 to 38.2) in the BI 1015550 group and –59.2 ml (95% credible interval, –111.8 to –17.9) in the placebo group (median difference, 62.4 ml; 95% credible interval, 6.3 to 125.5; probability that BI 1015550 was superior to placebo, 0.986). A mixed model with repeated measures analysis provided results that were consistent with those of the Bayesian analysis. The most frequent adverse event was diarrhea. A total of 13 patients discontinued BI 1015550 treatment owing to adverse events. The percentages of patients with serious adverse events or severe adverse events were similar in the two trial groups.

Conclusions

In this placebo-controlled trial, treatment with BI 1015550, either alone or with background use of an antifibrotic agent, prevented a decrease in lung function in patients with idiopathic pulmonary fibrosis.

DOI: 10.1056/NEJMoa2201737

Source: https://www.nejm.org/doi/full/10.1056/NEJMoa2201737

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：176.079
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