吡非尼酮治疗无法分类的间质性肺疾病：伴用霉酚酸酯和/或既往使用皮质类固醇的亚组分析。
Pirfenidone in Unclassifiable Interstitial Lung Disease: A Subgroup Analysis by Concomitant Mycophenolate Mofetil and/or Previous Corticosteroid Use.
机构信息
Department of Pulmonology and Critical Care Medicine, Center for Interstitial and Rare Lung Diseases, Thoraxklinik, University of Heidelberg, Roentgen Street 1, 69126, Heidelberg, Germany.
German Center for Lung Research, Heidelberg, Germany.
出版信息
Adv Ther. 2022 Feb;39(2):1081-1095. doi: 10.1007/s12325-021-02009-w. Epub 2021 Dec 22.
INTRODUCTION
There are currently no approved treatments solely for unclassifiable interstitial lung disease (uILD); however, a recent trial showed this population can benefit from pirfenidone. We report a subgroup analysis of this trial to assess the effects of immunomodulators (concomitant mycophenolate mofetil [MMF] and/or previous corticosteroids) with pirfenidone in patients with uILD.
METHODS
This was a multicenter, international, double-blind, randomized, placebo-controlled phase II trial of patients with progressive fibrosing uILD (NCT03099187). Patients were randomized (1:1) to receive pirfenidone 2403 mg/day or placebo. This analysis assessed forced vital capacity (FVC) change from baseline measured using site spirometry (key secondary endpoint) and safety over 24 weeks by concomitant MMF use at randomization (pre-specified analysis) and/or previous corticosteroid use (post hoc analysis).
RESULTS
Overall, 253 patients were randomized, including 45 (17.8%) patients (pirfenidone, n = 23; placebo, n = 22) receiving concomitant MMF with/without previous corticosteroids (MMF subgroup); 79 (31.2%) patients (pirfenidone, n = 44; placebo, n = 35) receiving previous corticosteroids without MMF (corticosteroids/no-MMF subgroup); and 129 (51.0%) patients (pirfenidone, n = 60; placebo, n = 69) not receiving concomitant MMF or previous corticosteroids (no-corticosteroids/no-MMF subgroup). At 24 weeks, difference in mean (95% confidence interval) FVC change from baseline between pirfenidone and placebo was - 55.4 mL (- 206.7, 96.0; P = 0.4645) in the MMF subgroup; 128.4 mL (- 6.4, 263.3; P = 0.0617) in the corticosteroids/no-MMF subgroup; and 115.5 mL (35.1, 195.9; P = 0.0052) in the no-corticosteroids/no-MMF subgroup. All subgroups generally exhibited a similar pattern of treatment-emergent adverse events.
CONCLUSION
Although limited by design and small sample sizes, this analysis suggests pirfenidone may be less effective in patients with uILD receiving concomitant MMF, whereas a beneficial treatment effect was observed in patients not receiving concomitant MMF regardless of previous corticosteroid use. Pirfenidone was well tolerated regardless of MMF and/or corticosteroid use.
TRIAL REGISTRATION NUMBER
ClinicalTrials.gov: NCT03099187.
介绍
目前尚无专门针对不可分类间质性肺病（uILD）的治疗方法；然而，最近的一项试验表明，此类人群可以从吡非尼酮中获益。我们报告了该试验的一个亚组分析，以评估免疫调节剂（同时使用霉酚酸酯和/或既往皮质类固醇）与 uILD 患者的吡非尼酮联合使用的效果。
方法
这是一项多中心、国际、双盲、随机、安慰剂对照的 II 期临床试验，纳入了进展性纤维化 uILD 患者（NCT03099187）。患者按 1:1 随机分配接受吡非尼酮 2403mg/天或安慰剂。该分析评估了基线时使用站点肺活量计测量的用力肺活量（FVC）变化（主要次要终点），以及 24 周时的安全性，通过随机时同时使用霉酚酸酯（预先指定的分析）和/或既往皮质类固醇使用（事后分析）进行评估。
结果
总体而言，253 名患者被随机分组，包括 45 名（17.8%）患者（吡非尼酮组，n=23；安慰剂组，n=22）同时接受霉酚酸酯联合/不联合既往皮质类固醇治疗（MMF 亚组）；79 名（31.2%）患者（吡非尼酮组，n=44；安慰剂组，n=35）接受既往皮质类固醇治疗而未使用霉酚酸酯（皮质类固醇/无 MMF 亚组）；129 名（51.0%）患者（吡非尼酮组，n=60；安慰剂组，n=69）未同时接受 MMF 或既往皮质类固醇治疗（无皮质类固醇/无 MMF 亚组）。24 周时，与安慰剂相比，吡非尼酮治疗的平均（95%置信区间）FVC 从基线变化的差异在 MMF 亚组中为-55.4mL（-206.7，96.0；P=0.4645）；在皮质类固醇/无 MMF 亚组中为 128.4mL（-6.4，263.3；P=0.0617）；在无皮质类固醇/无 MMF 亚组中为 115.5mL（35.1，195.9；P=0.0052）。所有亚组通常表现出相似的治疗出现不良事件模式。
结论
尽管设计和样本量较小，但该分析表明，吡非尼酮在同时接受 MMF 治疗的 uILD 患者中的疗效可能较低，而在未接受同时接受 MMF 治疗的患者中，无论是否使用过皮质类固醇，均观察到有益的治疗效果。无论是否使用 MMF 和/或皮质类固醇，吡非尼酮均具有良好的耐受性。
试验注册
ClinicalTrials.gov：NCT03099187。
Zotero 插件