抗酸剂治疗与特发性肺纤维化疾病结局：汇总分析。
Antacid therapy and disease outcomes in idiopathic pulmonary fibrosis: a pooled analysis.
机构信息
Center for Interstitial and Rare Lung Diseases, Pneumology and Respiratory Critical Care Medicine, Thoraxklinik, University of Heidelberg, Heidelberg, Germany; Translational Lung Research Center Heidelberg, German Center for Lung Research, Heidelberg, Germany.
Unit for Interstitial Lung Diseases, Department of Respiratory Medicine, University Hospitals, Leuven, Belgium.
出版信息
Lancet Respir Med. 2016 May;4(5):381-9. doi: 10.1016/S2213-2600(16)00067-9. Epub 2016 Mar 31.
BACKGROUND
Gastro-oesophageal reflux disease is a potential risk factor for the development and progression of idiopathic pulmonary fibrosis (IPF). We aimed to investigate the effect of antacid therapy on disease progression in patients randomly assigned to placebo through analysis of three large, phase 3 trials of pirfenidone in IPF.
METHODS
Patients with IPF from the placebo groups of three trials of pirfenidone (CAPACITY 004, CAPACITY 006, and ASCEND) were included in this post-hoc analysis. We analysed effects of antacid therapy use from baseline for pulmonary function, exercise tolerance, survival, hospital admission, and adverse events for 52 weeks with and without adjustment for potential confounders. The primary endpoint, disease progression by 1 year, was defined as a decrease in predicted forced vital capacity (FVC) by 10% or more, a decrease in 6 min walk distance (6MWD) by 50 m or more, or death. We did survival analyses with the Kaplan-Meier estimator and evaluated using the log-rank test.
FINDINGS
Of 624 patients, 291 (47%) received antacid therapy and 333 (53%) did not. At 52 weeks, we noted no significant difference between groups for disease progression (114 [39%] for antacid therapy vs 141 [42%] for no antacid therapy, p=0·4844). Rates also did not differ for all-cause mortality (20 [7%] vs 22 [7%], p=0·8947), IPF-related mortality (11 [4%] vs 17 [5%]; p=0·4251), absolute FVC decrease by 10% or more (49 [17%] vs 64 [19%]; p=0·4411), or mean observed change in FVC (% predicted -4·9% [SD 6·4] vs -5·5% [7·2], p=0·3355; observed volume -0·2 L [0·3] vs -0·2 L [0·3], p=0·4238). The rate of hospital admission was non-significantly higher in the antacid therapy group (65 [22%] vs 54 [16%]; p=0·0522). When stratified by baseline FVC (<70% or ≥70%), disease progression, mortality, FVC, 6MWD, and hospital admission did not differ between groups. Adverse events were similar between treatment and no treatment groups; however, overall infections (107 [74%] vs 101 [62%]; p=0·0174) and pulmonary infections (20 [14%] vs 10 [6%]; p=0·0214) were higher in patients with advanced IPF (ie, FVC <70%) who were treated with antacids than not treated with antacids.
INTERPRETATION
Antacid therapy did not improve outcomes in patients with IPF and might potentially be associated with an increased risk of infection in those with advanced disease.
FUNDING
F Hoffmann-La Roche.
背景
胃食管反流病是特发性肺纤维化（IPF）发生和进展的潜在危险因素。我们旨在通过对吡非尼酮治疗特发性肺纤维化的三项大型 3 期临床试验的安慰剂组进行分析，研究抗酸治疗对疾病进展的影响。
方法
本研究纳入了来自吡非尼酮三项试验（CAPACITY 004、CAPACITY 006 和 ASCEND）安慰剂组的 IPF 患者。我们分析了基线时使用抗酸剂治疗对肺功能、运动耐量、生存、住院和不良事件的影响，分析时间为 52 周，并根据潜在混杂因素进行了调整。主要终点为 1 年内疾病进展，定义为用力肺活量（FVC）预计值下降 10%或以上、6 分钟步行距离（6MWD）下降 50 m 或以上，或死亡。我们使用 Kaplan-Meier 估计值进行生存分析，并使用对数秩检验进行评估。
结果
在 624 名患者中，291 名（47%）接受了抗酸治疗，333 名（53%）未接受抗酸治疗。在 52 周时，我们发现两组之间疾病进展无显著差异（抗酸治疗组 114 例[39%]，无抗酸治疗组 141 例[42%]，p=0.4844）。全因死亡率（抗酸治疗组 20 例[7%]，无抗酸治疗组 22 例[7%]，p=0.8947）、与 IPF 相关的死亡率（抗酸治疗组 11 例[4%]，无抗酸治疗组 17 例[5%]，p=0.4251）、FVC 预计值下降 10%或更多（抗酸治疗组 49 例[17%]，无抗酸治疗组 64 例[19%]，p=0.4411）或 FVC 实际变化百分比（-4.9%[SD 6.4] vs -5.5%[7.2]，p=0.3355；观察到的体积-0.2 L[0.3] vs -0.2 L[0.3]，p=0.4238）也无显著差异。抗酸治疗组的住院率（22%[65 例]）显著高于无抗酸治疗组（16%[54 例]），但无统计学差异（p=0.0522）。当按基线 FVC（<70%或≥70%）分层时，两组间疾病进展、死亡率、FVC、6MWD 和住院率无差异。治疗组和未治疗组的不良事件相似；然而，在接受抗酸治疗的晚期 IPF（即 FVC<70%）患者中，总体感染（抗酸治疗组 107 例[74%]，无抗酸治疗组 101 例[62%]，p=0.0174）和肺部感染（抗酸治疗组 20 例[14%]，无抗酸治疗组 10 例[6%]，p=0.0214）的发生率更高。
结论
抗酸治疗并未改善 IPF 患者的预后，并且可能与晚期疾病患者的感染风险增加有关。
资金
F Hoffmann-La Roche。
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