Luca Richeldi1, Vincent Cottin2, Roland M du Bois3, Moisés Selman4, Toshio Kimura5, Zelie Bailes6, Rozsa Schlenker-Herceg7, Susanne Stowasser8, Kevin K Brown9. 1. National Institute for Health Research, Southampton Respiratory Biomedical Research Unit and Clinical and Experimental Sciences, University of Southampton, University Road, Southampton, SO17 1BJ, UK. Electronic address: L.Richeldi@soton.ac.uk. 2. Louis Pradel Hospital, Claude Bernard University Lyon 1, 28 Avenue du Doyen Lepine, 69677, Bron Cedex, Lyon, France. Electronic address: vincent.cottin@chu-lyon.fr. 3. Imperial College, London, SW7 2AZ, UK. Electronic address: ron@du-bois.co.uk. 4. Instituto Nacional de Enfermedades Respiratorias, Calz. de Tlalpan 4502, Tlalpan, Mexico City, D.F., Mexico. Electronic address: mselmanl@yahoo.com.mx. 5. Boehringer Ingelheim Pharma GmbH & Co. KG, Binger Str. 173, 55216, Ingelheim am Rhein, Germany. Electronic address: toshio.kimura@boehringer-ingelheim.com. 6. Boehringer Ingelheim Ltd., Ellesfield Avenue, Bracknell, West Berkshire, RG12 8YS, UK. Electronic address: zelie.bailes@boehringer-ingelheim.com. 7. Boehringer Ingelheim Pharmaceuticals Inc., 900 Ridgebury Road, Ridgefield, CT, 06877, USA. Electronic address: rozsa.schlenker-herceg@boehringer-ingelheim.com. 8. Boehringer Ingelheim Pharma GmbH & Co. KG, Binger Str. 173, 55216, Ingelheim am Rhein, Germany. Electronic address: susanne.stowasser@boehringer-ingelheim.com. 9. National Jewish Health, 1400 Jackson St, Denver, CO, 80206, USA. Electronic address: brownk@njhealth.org.
Abstract
BACKGROUND AND PURPOSE: The Phase II TOMORROW trial and two Phase III INPULSIS(®) trials investigated the efficacy and safety of nintedanib versus placebo in patients with idiopathic pulmonary fibrosis (IPF). To obtain an overall estimate of the treatment effect of nintedanib 150 mg twice daily (bid), pooled and meta-analyses of data from these three trials were conducted. METHODS: Pooled and meta-analyses were conducted for annual rate of decline in forced vital capacity (FVC), time to first acute exacerbation, change from baseline in St George's Respiratory Questionnaire (SGRQ) total score and mortality over 52 weeks. RESULTS: 1231 patients (nintedanib n = 723, placebo n = 508) were included in the pooled analysis. Adjusted annual rate of decline in FVC was -112.4 mL/year with nintedanib and -223.3 mL/year with placebo (difference: 110.9 mL/year [95% CI: 78.5, 143.3]; p < 0.0001). The hazard ratio for time to first acute exacerbation was 0.53 (95% CI: 0.34, 0.83; p = 0.0047). Adjusted mean change from baseline in SGRQ score at week 52 was 2.92 with nintedanib and 4.97 with placebo (difference: -2.05 [95% CI: -3.59, -0.50]; p = 0.0095). Hazard ratios for time to all-cause and on-treatment mortality were 0.70 (95% CI: 0.46, 1.08; p = 0.0954) and 0.57 (95% CI: 0.34, 0.97; p = 0.0274), respectively, in favour of nintedanib. The meta-analysis was generally consistent with the pooled analysis. Diarrhoea was the most frequent adverse event in the nintedanib group (61.5% of patients treated with nintedanib versus 17.9% of patients treated with placebo). CONCLUSION: Nintedanib has a beneficial effect on slowing disease progression in patients with IPF.
BACKGROUND AND PURPOSE: The Phase II TOMORROW trial and two Phase III INPULSIS(®) trials investigated the efficacy and safety of nintedanib versus placebo in patients with idiopathic pulmonary fibrosis (IPF). To obtain an overall estimate of the treatment effect of nintedanib 150 mg twice daily (bid), pooled and meta-analyses of data from these three trials were conducted. METHODS: Pooled and meta-analyses were conducted for annual rate of decline in forced vital capacity (FVC), time to first acute exacerbation, change from baseline in St George's Respiratory Questionnaire (SGRQ) total score and mortality over 52 weeks. RESULTS: 1231 patients (nintedanib n = 723, placebo n = 508) were included in the pooled analysis. Adjusted annual rate of decline in FVC was -112.4 mL/year with nintedanib and -223.3 mL/year with placebo (difference: 110.9 mL/year [95% CI: 78.5, 143.3]; p < 0.0001). The hazard ratio for time to first acute exacerbation was 0.53 (95% CI: 0.34, 0.83; p = 0.0047). Adjusted mean change from baseline in SGRQ score at week 52 was 2.92 with nintedanib and 4.97 with placebo (difference: -2.05 [95% CI: -3.59, -0.50]; p = 0.0095). Hazard ratios for time to all-cause and on-treatment mortality were 0.70 (95% CI: 0.46, 1.08; p = 0.0954) and 0.57 (95% CI: 0.34, 0.97; p = 0.0274), respectively, in favour of nintedanib. The meta-analysis was generally consistent with the pooled analysis. Diarrhoea was the most frequent adverse event in the nintedanib group (61.5% of patients treated with nintedanib versus 17.9% of patients treated with placebo). CONCLUSION:Nintedanib has a beneficial effect on slowing disease progression in patients with IPF.
Authors: Coenraad F N Koegelenberg; Gillian M Ainslie; Keertan Dheda; Brian W Allwood; Michelle L Wong; Umesh G Lalloo; Mohamed S Abdool-Gaffar; Hoosain Khalfey; Elvis M Irusen Journal: J Thorac Dis Date: 2016-12 Impact factor: 2.895
Authors: Sarah Geerts; Wim Wuyts; Ellen De Langhe; Jan Lenaerts; Jonas Yserbyt Journal: Sarcoidosis Vasc Diffuse Lung Dis Date: 2017-04-28 Impact factor: 0.670
Authors: Marilyn K Glassberg; Julia Minkiewicz; Rebecca L Toonkel; Emmanuelle S Simonet; Gustavo A Rubio; Darcy DiFede; Shirin Shafazand; Aisha Khan; Marietsy V Pujol; Vincent F LaRussa; Lisa H Lancaster; Glenn D Rosen; Joel Fishman; Yolanda N Mageto; Adam Mendizabal; Joshua M Hare Journal: Chest Date: 2016-11-24 Impact factor: 9.410
Authors: Ashley R Rackow; David J Nagel; Claire McCarthy; Jennifer Judge; Shannon Lacy; Margaret A T Freeberg; Thomas H Thatcher; R Matthew Kottmann; Patricia J Sime Journal: Eur Respir J Date: 2020-11-26 Impact factor: 16.671
Authors: Junsuk Ko; Tingting Mills; Jingjing Huang; Ning-Yuan Chen; Tinne C J Mertens; Scott D Collum; Garam Lee; Yu Xiang; Leng Han; Yang Zhou; Chun Geun Lee; Jack A Elias; Soma S K Jyothula; Keshava Rajagopal; Harry Karmouty-Quintana; Michael R Blackburn Journal: J Biol Chem Date: 2019-09-05 Impact factor: 5.157
Authors: Elizabeth F Redente; Martin A Aguilar; Bart P Black; Benjamin L Edelman; Ali N Bahadur; Stephen M Humphries; David A Lynch; Lutz Wollin; David W H Riches Journal: Am J Physiol Lung Cell Mol Physiol Date: 2018-03-15 Impact factor: 5.464