Mark Fisher1, Steven D Nathan2, Christian Hill3, Jade Marshall3, Fred Dejonckheere4, Per-Olof Thuresson4, Toby M Maher5. 1. 1 St Albans, United Kingdom. 2. 2 Advanced Lung Disease and Transplant Program, Inova Fairfax Hospital, Falls Church, Virginia. 3. 3 MAP BioPharma, Cambridge, United Kingdom. 4. 4 F. Hoffmann-La Roche, Basel, Switzerland. 5. 5 Interstitial Lung Disease Unit, Royal Brompton Hospital/Imperial College London, London, United Kingdom.
Abstract
BACKGROUND: 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. OBJECTIVE: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: This analysis suggests that this population of patients with IPF has an improved life expectancy if treated with pirfenidone compared with BSC. DISCLOSURES: 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.
BACKGROUND: 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. OBJECTIVE: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: This analysis suggests that this population of patients with IPF has an improved life expectancy if treated with pirfenidone compared with BSC. DISCLOSURES: 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.
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