Nintedanib and immunomodulatory therapies in progressive fibrosing interstitial lung diseases.
Nintedanib and immunomodulatory therapies in progressive fibrosing interstitial lung diseases.
复制标题
DOI：
10.1186/s12931-021-01668-1
复制
发表时间：
2021-03-16
影响因子：
5.8
通讯作者：
INBUILD Trial Investigators
中科院分区：
文献类型：
--
作者：
Cottin V;Richeldi L;Rosas I;Otaola M;Song JW;Tomassetti S;Wijsenbeek M;Schmitz M;Coeck C;Stowasser S;Schlenker-Herceg R;Kolb M;INBUILD Trial Investigators
在慢性纤维化间质性肺疾病（ILD）和进行性表型患者中进行的INBUILD试验中，尼达尼布降低了ILD进展率，且大多数患者的不良事件可管理。我们研究了免疫调节治疗对尼达尼布疗效和安全性的潜在影响。患有除特发性肺纤维化以外的纤维化ILD的受试者，尽管在临床实践中进行了管理，但在过去24个月内仍显示ILD进展，随机接受尼达尼布或安慰剂治疗。某些免疫调节治疗在前6个月受到限制。我们事后分析了按基线时糖皮质激素使用情况和排除受试者或开始限制性免疫调节或抗纤维化治疗后进行的用力肺活量（FVC）测量结果的分析中的亚组在52周内的FVC下降率。在663例受试者中，361例（54.4%）在基线时使用糖皮质激素（353例剂量≤ 20 mg/天）。在安慰剂组中，基线时接受糖皮质激素治疗的受试者52周内校正的FVC下降率（mL/年）在数值上大于未接受糖皮质激素治疗的受试者（− 206.4 [SE 20.2] vs − 165.8 [21.9]）。尼达尼布组与安慰剂组之间的差异，基线时使用糖皮质激素的受试者为133.3（95% CI 76.6，190.0）mL/年，未使用糖皮质激素的受试者为76.1（15.0，137.2）mL/年（相互作用P = 0.18）。在排除受试者或开始限制性免疫调节或抗纤维化治疗后测量值的分析中，尼达尼布对降低FVC下降率的作用与主要分析相似。在基线或试验药物治疗期间使用和未使用禁用或限制治疗的受试者之间，尼达尼布的不良事件特征相似。在进行性纤维化ILD患者中，尼达尼布降低FVC下降的作用不受免疫调节治疗的影响。Nursing可与免疫调节治疗联合用于进行性纤维化ILD患者。试用注册ClinicalTrials.gov，NCT 02999178。2016年12月21日注册，https://clinicaltrials.gov/ct2/show/NCT02999178在线版本包含补充材料，可通过10.1186/s12931-021-01668-1获得。
In the INBUILD trial in patients with chronic fibrosing interstitial lung diseases (ILDs) and a progressive phenotype, nintedanib reduced the rate of ILD progression with adverse events that were manageable for most patients. We investigated the potential impact of immunomodulatory therapies on the efficacy and safety of nintedanib. Subjects with fibrosing ILDs other than idiopathic pulmonary fibrosis, who had shown progression of ILD within the prior 24 months despite management in clinical practice, were randomized to receive nintedanib or placebo. Certain immunomodulatory therapies were restricted for the first 6 months. We analyzed post-hoc the rate of decline in forced vital capacity (FVC) over 52 weeks in subgroups by glucocorticoid use at baseline and in analyses excluding subjects or FVC measurements taken after initiation of restricted immunomodulatory or antifibrotic therapies. Of 663 subjects, 361 (54.4%) were taking glucocorticoids at baseline (353 at a dose of ≤ 20 mg/day). In the placebo group, the adjusted rate of decline in FVC (mL/year) over 52 weeks was numerically greater in subjects taking than not taking glucocorticoids at baseline (− 206.4 [SE 20.2] vs − 165.8 [21.9]). The difference between the nintedanib and placebo groups was 133.3 (95% CI 76.6, 190.0) mL/year in subjects taking glucocorticoids at baseline and 76.1 (15.0, 137.2) mL/year in subjects who were not (interaction P = 0.18). The effect of nintedanib on reducing the rate of FVC decline in analyses excluding subjects or measurements taken after initiation of restricted immunomodulatory or antifibrotic therapies was similar to the primary analysis. The adverse event profile of nintedanib was similar between subjects who did and did not use prohibited or restricted therapies at baseline or during treatment with trial drug. In patients with progressive fibrosing ILDs, the effect of nintedanib on reducing FVC decline was not influenced by the use of immunomodulatory therapies. Nintedanib can be used in combination with immunomodulatory therapies in patients with progressive fibrosing ILDs. Trial registration ClinicalTrials.gov, NCT02999178. Registered 21 December 2016, https://clinicaltrials.gov/ct2/show/NCT02999178 The online version contains supplementary material available at 10.1186/s12931-021-01668-1.
登录
查看更多内容
影响因子：
3.9
作者：
De Sadeleer, Laurens J.;Hermans, Frederik;Wuyts, Wim A.
通讯作者：
Wuyts, Wim A.
影响因子：
158.5
作者：
Distler, Oliver;Highland, Kristin B.;Maher, Toby M.
通讯作者：
Maher, Toby M.
DOI：
10.1056/nejmoa1113354
发表时间：
2012-05-24
期刊：
The New England journal of medicine
影响因子：
--
作者：
Idiopathic Pulmonary Fibrosis Clinical Research Network;Raghu G;Anstrom KJ;King TE Jr;Lasky JA;Martinez FJ
通讯作者：
Martinez FJ
DOI：
10.1164/rccm.201608-1675pp
发表时间：
2017-09-15
影响因子：
24.7
作者：
Salisbury, Margaret L.;Myers, Jeffrey L.;Flaherty, Kevin R.
通讯作者：
Flaherty, Kevin R.
影响因子：
24.3
作者：
Wells, Athol U.;Brown, Kevin K.;Thannickal, Victor J.
通讯作者：
Thannickal, Victor J.