Center for Interstitial and Rare Lung Diseases, Pneumology and Respiratory Care Medicine, Thoraxklinik, University of Heidelberg, Röntgenstraße 1, 69120, Heidelberg, Germany.
Boehringer Ingelheim International GmbH, Ingelheim am Rhein, Germany.
Respir Res. 2019 Apr 11;20(1):71. doi: 10.1186/s12931-019-1037-7.
Given the broad definition of an acute exacerbation of IPF, it is likely that acute exacerbations are heterogeneous in their aetiology, severity and clinical course. We used pooled data from the INPULSIS® trials of nintedanib versus placebo to investigate whether acute exacerbations reported as serious adverse events were associated with higher mortality than those reported as non-serious adverse events and to assess the effect of nintedanib on these types of events.
Adverse events considered by an investigator to be an acute exacerbation were adjudicated as a confirmed acute exacerbation, suspected acute exacerbation, or not an acute exacerbation. Time to first investigator-reported acute exacerbation or confirmed/suspected acute exacerbation reported as a serious adverse event or non-serious adverse event over the 52-week treatment period was assessed post-hoc. Deaths were assessed based on data collected over the 52-week treatment period.
Of 63 patients who had ≥1 investigator-reported acute exacerbation, 48 (76.2%) had a first acute exacerbation reported as a serious adverse event. Thirty-six (3.4%) patients had ≥1 confirmed/suspected acute exacerbation, of whom 31 had a first event reported as a serious adverse event. Investigator-reported acute exacerbations reported as serious adverse events occurred in 23 patients in the nintedanib group and 26 in the placebo group. Confirmed/suspected acute exacerbations reported as serious adverse events occurred in 10 and 21 patients in these groups, respectively. Nintedanib significantly reduced the risk of a first acute exacerbation reported as a serious adverse event (HR 0.57 [95% CI: 0.32, 0.99]; p = 0.0476) and the risk of a first confirmed/suspected acute exacerbation reported as a serious adverse event (HR 0.30 [95% CI: 0.14, 0.64]; p = 0.0019) versus placebo. A higher proportion of patients with investigator-reported acute exacerbations reported as serious adverse events died than patients with acute exacerbations reported as non-serious adverse events (61.2% versus 7.1%).
Different severities of acute exacerbation of IPF may exist. Acute exacerbations reported as serious adverse events in the INPULSIS® trials were associated with high mortality. Nintedanib significantly reduced the risk of acute exacerbations reported as serious adverse events.
ClinicalTrials.gov NCT01335464 and NCT01335477 .
鉴于特发性肺纤维化急性加重的广泛定义，其病因、严重程度和临床过程可能存在异质性。我们使用尼达尼布与安慰剂的 INPULSIS®试验的汇总数据，调查报告为严重不良事件的急性加重是否与死亡率高于报告为非严重不良事件的急性加重相关，并评估尼达尼布对这些类型事件的影响。
研究者认为是急性加重的不良事件被判定为确诊的急性加重、疑似急性加重或非急性加重。对首次研究者报告的急性加重或在 52 周治疗期间报告为严重或非严重不良事件的确诊/疑似急性加重的时间进行事后评估。根据 52 周治疗期间收集的数据评估死亡情况。
在 63 名至少有 1 次研究者报告的急性加重的患者中，48 名（76.2%）的首次急性加重报告为严重不良事件。36 名（3.4%）患者至少有 1 次确诊/疑似急性加重，其中 31 次首次事件报告为严重不良事件。尼达尼布组有 23 名患者报告了研究者报告的严重不良事件急性加重，安慰剂组有 26 名患者报告了严重不良事件急性加重。在这些组中，分别有 10 名和 21 名患者报告了确诊/疑似的严重不良事件急性加重。尼达尼布显著降低了首次报告为严重不良事件的急性加重风险（HR 0.57 [95% CI: 0.32, 0.99]；p=0.0476）和首次确诊/疑似严重不良事件急性加重的风险（HR 0.30 [95% CI: 0.14, 0.64]；p=0.0019）与安慰剂相比。报告为严重不良事件的研究者报告的急性加重患者的死亡率高于报告为非严重不良事件的急性加重患者（61.2%比 7.1%）。
可能存在不同严重程度的特发性肺纤维化急性加重。在 INPULSIS®试验中报告为严重不良事件的急性加重与高死亡率相关。尼达尼布显著降低了报告为严重不良事件的急性加重风险。
ClinicalTrials.gov NCT01335464 和 NCT01335477。
Zotero 插件