特发性肺纤维化患者用力肺活量出现具有临床意义的下降后继续使用吡非尼酮治疗的效果：来自三项3期试验的数据分析

Effect of continued treatment with pirfenidone following clinically meaningful declines in forced vital capacity: analysis of data from three phase 3 trials in patients with idiopathic pulmonary fibrosis.

作者信息

Nathan Steven D, Albera Carlo, Bradford Williamson Z, Costabel Ulrich, du Bois Roland M, Fagan Elizabeth A, Fishman Robert S, Glaspole Ian, Glassberg Marilyn K, Glasscock Kenneth F, King Talmadge E, Lancaster Lisa, Lederer David J, Lin Zhengning, Pereira Carlos A, Swigris Jeffrey J, Valeyre Dominique, Noble Paul W, Wells Athol U

机构信息

Inova Fairfax Hospital, Heart and Lung Transplant Center, Falls Church, Virginia, USA.

Department of Clinical and Biological Sciences, University of Turin, Turin, Italy.

出版信息

Thorax. 2016 May;71(5):429-35. doi: 10.1136/thoraxjnl-2015-207011. Epub 2016 Mar 11.

DOI:10.1136/thoraxjnl-2015-207011

PMID:26968970

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC4862066/

Abstract

BACKGROUND

The assessment of treatment response in idiopathic pulmonary fibrosis (IPF) is complicated by the variable clinical course. We examined the variability in the rate of disease progression and evaluated the effect of continued treatment with pirfenidone in patients who experienced meaningful progression during treatment.

METHODS

The source population included patients enrolled in the ASCEND and CAPACITY trials (N=1247). Pearson's correlation coefficients were used to characterise the relationship between changes in FVC during consecutive 6-month intervals in the placebo population. Outcomes following a ≥10% decline in FVC were evaluated by comparing the proportion of patients in the pirfenidone and placebo groups who experienced a ≥10% decline in FVC or death during the subsequent 6 months.

RESULTS

A weak negative correlation was observed between FVC changes during consecutive intervals in the placebo population (coefficient, -0.146, p<0.001), indicating substantial variability. Thirty-four (5.5%) and 68 (10.9%) patients in the pirfenidone and placebo groups, respectively, experienced a ≥10% decline in FVC by month 6. During the subsequent 6 months, fewer patients in the pirfenidone group compared with placebo experienced a ≥10% decline in FVC or death (5.9% vs 27.9%; relative difference, 78.9%). There was one (2.9%) death in the pirfenidone group and 14 (20.6%) deaths in the placebo group (relative difference, 85.7%).

CONCLUSIONS

Longitudinal FVC data from patients with IPF showed substantial intrasubject variability, underscoring the inability to reliably assess therapeutic response using serial FVC trends. In patients who progressed during treatment, continued treatment with pirfenidone resulted in a lower risk of subsequent FVC decline or death.

TRIAL REGISTRATION NUMBERS

NCT01366209, NCT00287729, NCT00287716.

摘要

背景

特发性肺纤维化（IPF）治疗反应的评估因临床病程多变而变得复杂。我们研究了疾病进展速率的变异性，并评估了在治疗期间出现显著进展的患者中继续使用吡非尼酮治疗的效果。

方法

源人群包括参加ASCEND和CAPACITY试验的患者（N = 1247）。使用Pearson相关系数来描述安慰剂组中连续6个月间隔内用力肺活量（FVC）变化之间的关系。通过比较吡非尼酮组和安慰剂组中在随后6个月内FVC下降≥10%或死亡的患者比例，评估FVC下降≥10%后的结局。

结果

在安慰剂组中，连续间隔内的FVC变化之间观察到弱负相关（系数为-0.146，p < 0.001），表明存在显著变异性。到第6个月时，吡非尼酮组和安慰剂组分别有34例（5.5%）和68例（10.9%）患者FVC下降≥10%。在随后的6个月中，与安慰剂组相比，吡非尼酮组中FVC下降≥10%或死亡的患者更少（5.9%对27.9%；相对差异为78.9%）。吡非尼酮组有1例（2.9%）死亡，安慰剂组有14例（20.6%）死亡（相对差异为85.7%）。