特发性肺纤维化的抗酸治疗：来自 INPULSIS®试验的见解。
Anti-acid therapy in idiopathic pulmonary fibrosis: insights from the INPULSIS® trials.
机构信息
Ruhrlandklinik, University Hospital, University of Duisburg-Essen, Essen, Germany.
Medizinische Klinik und Poliklinik V, University of Munich (LMU) and Asklepios Klinik München-Gauting, Member of the German Center for Lung Research, Munich, Germany.
出版信息
Respir Res. 2018 Sep 3;19(1):167. doi: 10.1186/s12931-018-0866-0.
BACKGROUND
The benefits and risks of anti-acid medication in patients with idiopathic pulmonary fibrosis (IPF) remain a topic of debate. We investigated whether use of anti-acid medication at baseline was associated with differences in the natural course of disease or influenced the treatment effect of nintedanib in patients with IPF.
METHODS
Post-hoc analyses of outcomes in patients receiving versus not receiving anti-acid medication (proton pump or histamine-2 receptor inhibitor) at baseline using pooled data from the two Phase III randomized placebo-controlled INPULSIS® trials of nintedanib in patients with IPF.
RESULTS
At baseline, 406 patients were receiving anti-acid medication (244 nintedanib; 162 placebo) and 655 were not (394 nintedanib; 261 placebo). In an analysis of the natural course of IPF by anti-acid medication use at baseline, the adjusted annual rate of decline in FVC was - 252.9 mL/year in placebo-treated patients who were receiving anti-acid medication at baseline and - 205.4 mL/year in placebo-treated patients who were not (difference of - 47.5 mL/year [95% CI: -105.1, 10.1]; p = 0.1057). In an analysis of the potential influence of anti-acid medication use on the treatment effect of nintedanib, the adjusted annual rates of decline in FVC were - 124.4 mL/year in the nintedanib group and - 252.9 mL/year in the placebo group (difference of 128.6 mL/year [95% CI: 74.9, 182.2]) in patients who were receiving anti-acid medication at baseline and - 107.0 mL/year in the nintedanib group and - 205.3 mL/year in the placebo group (difference of 98.3 mL/year [95% CI: 54.1, 142.5]) in patients who were not (treatment-by-time-by-subgroup interaction p = 0.3869). The proportions of patients who had ≥1 investigator-reported acute exacerbation were 11.7% and 5.0% in placebo-treated patients, and 4.9% and 4.8% of nintedanib-treated patients, among patients who were and were not receiving anti-acid medication at baseline, respectively.
CONCLUSIONS
In post-hoc analyses of data from the INPULSIS® trials, anti-acid medication use at baseline was not associated with a more favorable course of disease, and did not impact the treatment effect of nintedanib, in patients with IPF.
TRIAL REGISTRATION
ClinicalTrials.gov identifiers: NCT01335464 and NCT01335477 .
背景
抗酸药物在特发性肺纤维化（IPF）患者中的获益和风险仍是一个有争议的话题。我们研究了基线时使用抗酸药物是否与疾病自然病程的差异有关，或是否影响 IPF 患者尼达尼布的治疗效果。
方法
使用尼达尼布治疗 IPF 的两项 III 期随机安慰剂对照 INPULSIS®试验的汇总数据，对基线时接受（质子泵或组胺 2 受体抑制剂）或不接受抗酸药物治疗的患者的结局进行事后分析。
结果
基线时，406 名患者正在接受抗酸药物治疗（244 名尼达尼布；162 名安慰剂），655 名患者未接受抗酸药物治疗（394 名尼达尼布；261 名安慰剂）。在基线时使用抗酸药物治疗的 IPF 自然病程分析中，接受安慰剂治疗且基线时正在接受抗酸药物治疗的患者的 FVC 年下降率为-252.9 mL/年，而未接受安慰剂治疗且基线时未接受抗酸药物治疗的患者的 FVC 年下降率为-205.4 mL/年（差异为-47.5 mL/年[95%CI：-105.1，10.1]；p=0.1057）。在分析抗酸药物使用对尼达尼布治疗效果的潜在影响时，接受尼达尼布治疗的患者的 FVC 年下降率为-124.4 mL/年，接受安慰剂治疗的患者的 FVC 年下降率为-252.9 mL/年（差异为 128.6 mL/年[95%CI：74.9，182.2]），而基线时接受抗酸药物治疗的患者的 FVC 年下降率为-107.0 mL/年，接受安慰剂治疗的患者的 FVC 年下降率为-205.3 mL/年（差异为 98.3 mL/年[95%CI：54.1，142.5]）。在基线时接受或不接受抗酸药物治疗的患者中，接受尼达尼布治疗的患者中有≥1 例研究者报告的急性加重的比例分别为 11.7%和 5.0%，接受安慰剂治疗的患者分别为 4.9%和 4.8%。
结论
在 INPULSIS®试验数据的事后分析中，基线时使用抗酸药物与疾病更有利的病程无关，也不影响 IPF 患者尼达尼布的治疗效果。
试验注册
ClinicalTrials.gov 标识符：NCT01335464 和 NCT01335477。
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