1 St Albans, United Kingdom.
2 Advanced Lung Disease and Transplant Program, Inova Fairfax Hospital, Falls Church, Virginia.
J Manag Care Spec Pharm. 2017 Mar;23(3-b Suppl):S17-S24. doi: 10.18553/jmcp.2017.23.3-b.s17.
Conducting an adequately powered survival study in idiopathic pulmonary fibrosis (IPF) is challenging due to the rare nature of the disease and the need for extended follow-up. Consequently, registration trials of IPF treatments have not been designed to estimate long-term survival.
To predict life expectancy for patients with IPF receiving pirfenidone versus best supportive care (BSC) in a population that met the inclusion criteria of patients enrolled in the ASCEND and CAPACITY trials.
Kaplan-Meier survival data for pirfenidone and BSC were obtained from randomized controlled clinical studies (CAPACITY, ASCEND), an open-label extension study (RECAP), and the Inova Fairfax Hospital database. Data from the Inova registry were matched to the inclusion criteria of the CAPACITY and ASCEND trials. Life expectancy was estimated by the area under the curve of parametric survival distributions fit to the Kaplan-Meier data.
Mean (95% confidence interval) life expectancy was calculated as 8.72 (7.65-10.15) years with pirfenidone and 6.24 (5.38-7.18) years with BSC. Therefore, pirfenidone improved life expectancy by 2.47 (1.26-4.17) years compared with BSC. In addition, treatment with pirfenidone recuperated 25% of the expected years of life lost due to IPF. Sensitivity analyses found that results were sensitive to the choice of parametric survival distribution, and alternative piecewise and parametric approaches.
This analysis suggests that this population of patients with IPF has an improved life expectancy if treated with pirfenidone compared with BSC.
This study was funded by InterMune International AG, a wholly owned Roche subsidiary since 2014. Fisher was previously employed by InterMune UK, a wholly owned Roche subsidiary, until July 2015. He is currently employed by FIECON, which has received funding from F. Hoffmann-La Roche for consulting services. Nathan has received consulting fees from Roche-Genentech and Boehringer Ingelheim. He is also on the speakers' bureau for Roche-Genentech and Boehringer Ingelheim and has received research funding from both companies. Hill was previously employed by InterMune UK until October 2014. Hill and Marshall are employees of MAP BioPharma, which has received funding from F. Hoffmann-La Roche for consulting services. Dejonckheere and Thuresson are employees of F. Hoffmann-La Roche. Maher has received grants, consulting fees, and speaker fees from GlaxoSmithKline and UCB, and grants from Novartis. He has also received consulting fees and speaker fees from AstraZeneca, Bayer, Biogen Idec, Boehringer Ingelheim, Cipla, Lanthio, InterMune International AG, F. Hoffmann-La Roche, Sanofi-Aventis, and Takeda. Maher is supported by a National Institute for Health Research Clinician Scientist Fellowship (NIHR Ref: CS: -2013-13-017). Study concept and design were contributed by Fisher, Hill, Marshall, and Dejonckheere. Fisher, Nathan, and Thuresson collected the data, along with Hill and Marshall. Data interpretation was performed by Fisher, Maher, Nathan, and Dejonckheere. The manuscript was written primarily by Fisher, along with Maher and Dejonckheere, and revised by Fisher and Maher, along with the other authors.
由于特发性肺纤维化 (IPF) 的罕见性质和需要进行长期随访，进行一项充分有力的生存研究具有挑战性。因此，IPF 治疗的注册试验并未设计用于估计长期生存率。
预测在符合 ASCEND 和 CAPACITY 试验入组标准的人群中，接受吡非尼酮与最佳支持治疗 (BSC) 的 IPF 患者的预期寿命。
从随机对照临床试验 (CAPACITY、ASCEND)、开放标签扩展研究 (RECAP) 和 Inova Fairfax 医院数据库获得吡非尼酮和 BSC 的 Kaplan-Meier 生存数据。Inova 注册处的数据与 CAPACITY 和 ASCEND 试验的纳入标准相匹配。通过适合 Kaplan-Meier 数据的参数生存分布的曲线下面积来估计预期寿命。
计算出使用吡非尼酮的平均 (95%置信区间) 预期寿命为 8.72 (7.65-10.15) 年，而使用 BSC 的平均预期寿命为 6.24 (5.38-7.18) 年。因此，与 BSC 相比，吡非尼酮将预期寿命延长了 2.47 (1.26-4.17) 年。此外，使用吡非尼酮治疗可恢复因 IPF 而损失的预期寿命的 25%。敏感性分析发现，结果对参数生存分布的选择以及替代分段和参数方法较为敏感。
这项分析表明，与 BSC 相比，接受吡非尼酮治疗的 IPF 患者的预期寿命有所提高。
这项研究由 InterMune International AG 资助，InterMune International AG 自 2014 年以来一直是罗氏的全资子公司。Fisher 曾在 InterMune UK 工作，InterMune UK 是罗氏的全资子公司，直至 2015 年 7 月。他目前受雇于 FICON，FICON 已从 Roche-Genentech 和 Boehringer Ingelheim 获得咨询服务的资金。Nathan 从 Roche-Genentech 和 Boehringer Ingelheim 获得咨询费，并为这两家公司进行研究资助。他也是 Roche-Genentech 和 Boehringer Ingelheim 的演讲者，并且从这两家公司获得了研究资金。Hill 曾在 2014 年 10 月之前在 InterMune UK 工作。Hill 和 Marshall 是 MAP BioPharma 的员工，MAP BioPharma 已从 Roche-Genentech 和 Boehringer Ingelheim 获得咨询服务的资金。Dejonckheere 和 Thuresson 是 Roche-Genentech 的员工。Maher 从 GlaxoSmithKline 和 UCB 获得了赠款、咨询费和演讲费，以及 Novartis 的赠款。他还从 AstraZeneca、Bayer、Biogen Idec、Boehringer Ingelheim、Cipla、Lanthio、InterMune International AG、F. Hoffmann-La Roche、Sanofi-Aventis 和 Takeda 获得了咨询费和演讲费。Maher 得到了国家卫生研究所临床科学家奖学金 (NIHR Ref: CS: -2013-13-017) 的支持。Fisher、Hill、Marshall 和 Dejonckheere 为研究的概念和设计做出了贡献。Fisher、Nathan 和 Thuresson 与 Hill 和 Marshall 一起收集了数据。Fisher、Maher、Nathan 和 Dejonckheere 对数据进行了解释。Fisher 与 Maher 和 Dejonckheere 一起主要撰写了手稿，Fisher 和 Maher 与其他作者一起对手稿进行了修订。
