BACKGROUND In the Phase III INPULSIS® trials, treatment of patients with idiopathic pulmonary fibrosis (IPF) with nintedanib significantly reduced the annual rate of decline in forced vital capacity (FVC) versus placebo, consistent with slowing disease progression. However, nintedanib was not associated with a benefit in health-related quality of life (HRQoL) assessed using the St George's respiratory questionnaire (SGRQ). We aimed to further examine the impact of IPF progression on HRQoL and symptoms, and to explore the effect of nintedanib on HRQoL in patients from the INPULSIS® trials stratified by clinical factors associated with disease progression. METHODS Patient-reported outcome (PRO) data from the INPULSIS® trials were included in three post hoc analyses. Two analyses used the pooled data set to examine PRO changes from baseline to week 52 according to 1) decline in FVC and 2) occurrence of acute exacerbations. In the third analysis, patients were stratified based on clinical indicators of disease progression (gender, age and physiology [GAP] stage; FVC % predicted; diffusing capacity of the lung for carbon monoxide [DLCO] % predicted; composite physiologic index [CPI]; and SGRQ total score) at baseline; median change from baseline was measured at 52 weeks and treatment groups were compared using the Wilcoxon two-sample test. RESULTS Data from 1061 patients (638 nintedanib, 423 placebo) were analyzed. Greater categorical decline from baseline in FVC % predicted over 52 weeks was associated with significant worsening of HRQoL and symptoms across all PRO measures. Acute exacerbations were associated with deterioration in HRQoL and worsened symptoms. In general, patients with advanced disease at baseline (defined as GAP II/III, FVC ≤ 80%, DLCO ≤ 40%, CPI >  45, or SGRQ > 40) experienced greater deterioration in PROs than patients with less-advanced disease. Among patients with advanced disease, compared with placebo, nintedanib slowed deterioration in several PROs; benefit was most apparent on the SGRQ (total and activity scores). CONCLUSIONS In patients with advanced IPF, compared with placebo, nintedanib slowed deterioration in HRQoL and symptoms as assessed by several PROs. HRQoL measures have a higher responsiveness to change in advanced disease and may lack sensitivity to capture change in patients with less-advanced IPF.

中文翻译：

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nintedanib治疗的IPF患者的健康相关生活质量和症状：INPULSIS®试验对患者报告结果的分析。

背景技术在III期INPULSIS®试验中，使用nintedanib治疗特发性肺纤维化（IPF）患者与安慰剂相比，可显着降低强迫肺活量（FVC）的年下降率，这与减缓疾病进展相一致。但是，使用圣乔治呼吸问卷（SGRQ）评估的nintedanib与健康相关生活质量（HRQoL）的益处无关。我们旨在进一步研究IPF进展对HRQoL和症状的影响，并探讨nintedanib对根据疾病进展相关临床因素分层的INPULSIS®试验患者对HRQoL的影响。方法来自INPULSIS®试验的患者报告结果（PRO）数据包括在三个事后分析中。两项分析使用汇总的数据集，根据1）FVC下降和2）急性加重的发生，检查从基线到第52周的PRO变化。在第三项分析中，根据疾病进展的临床指标（性别，年龄和生理学[GAP]分期；预测的FVC％；预测的肺对一氧化碳的扩散能力[DLCO]％；复合生理指标[CPI]）对患者进行分层；以及SGRQ总得分）。在52周时测量基线的中位数变化，并使用Wilcoxon两样本测试比较治疗组。结果分析了1061例患者（638例nintedanib，423例安慰剂）的数据。在52周内，预测的FVC％相对于基线的最大分类下降更大，与所有PRO措施中HRQoL和症状明显恶化有关。急性发作与HRQoL恶化和症状恶化有关。一般而言，基线时患有晚期疾病（定义为GAP II / III，FVC≤80％，DLCO≤40％，CPI> 45或SGRQ> 40）的患者，PRO的病情恶化程度较病情较轻的患者更大。在患有晚期疾病的患者中，与安慰剂相比，nintedanib减缓了一些PRO的恶化。好处在SGRQ上最明显（总得分和活动得分）。结论在晚期IPF患者中，与安慰剂相比，nintedanib减缓了HRQoL的恶化和一些PRO评估的症状。HRQoL措施对晚期疾病的变化具有较高的响应能力，对于IPF较差的患者，可能缺乏捕捉变化的敏感性。基线时患有晚期疾病（定义为GAP II / III，FVC≤80％，DLCO≤40％，CPI> 45或SGRQ> 40）的患者，PRO的恶化程度要比疾病进展程度较轻的患者更大。在患有晚期疾病的患者中，与安慰剂相比，nintedanib减缓了一些PRO的恶化。好处在SGRQ上最明显（总得分和活动得分）。结论在晚期IPF患者中，与安慰剂相比，nintedanib减缓了HRQoL的恶化和一些PRO评估的症状。HRQoL措施对晚期疾病的变化具有较高的响应能力，对于IPF较差的患者，可能缺乏捕捉变化的敏感性。基线时患有晚期疾病（定义为GAP II / III，FVC≤80％，DLCO≤40％，CPI> 45或SGRQ> 40）的患者，PRO的恶化程度要比疾病进展程度较轻的患者更大。在患有晚期疾病的患者中，与安慰剂相比，nintedanib减缓了一些PRO的恶化。好处在SGRQ上最明显（总得分和活动得分）。结论在晚期IPF患者中，与安慰剂相比，nintedanib减缓了HRQoL的恶化和一些PRO评估的症状。HRQoL措施对晚期疾病的变化具有较高的响应能力，对于IPF较差的患者，可能缺乏捕捉变化的敏感性。40）与病情较轻的患者相比，PRO的恶化更大。在患有晚期疾病的患者中，与安慰剂相比，nintedanib减缓了一些PRO的恶化。好处在SGRQ上最明显（总得分和活动得分）。结论在晚期IPF患者中，与安慰剂相比，nintedanib减缓了HRQoL的恶化和一些PRO评估的症状。HRQoL措施对晚期疾病的变化具有较高的响应能力，对于IPF较差的患者，可能缺乏捕捉变化的敏感性。40）与疾病较轻的患者相比，PRO的恶化更大。在患有晚期疾病的患者中，与安慰剂相比，nintedanib减缓了一些PRO的恶化。好处在SGRQ上最明显（总得分和活动得分）。结论在晚期IPF患者中，与安慰剂相比，nintedanib减缓了HRQoL的恶化和一些PRO评估的症状。HRQoL措施对晚期疾病的变化具有较高的响应能力，对于IPF较差的患者，可能缺乏捕捉变化的敏感性。如几位专家评估的那样，nintedanib减缓了HRQoL和症状的恶化。HRQoL措施对晚期疾病的变化具有较高的响应能力，对于IPF较差的患者，可能缺乏捕捉变化的敏感性。如几位专家评估的那样，nintedanib减缓了HRQoL和症状的恶化。HRQoL措施对晚期疾病的变化具有较高的响应能力，对于IPF较差的患者，可能缺乏捕捉变化的敏感性。