Kevin K Brown1, Kevin R Flaherty2, Vincent Cottin3, Ganesh Raghu4, Yoshikazu Inoue5, Arata Azuma6, John T Huggins7, Luca Richeldi8, Susanne Stowasser9, Wibke Stansen10, Rozsa Schlenker-Herceg11, Toby M Maher12, Athol U Wells13. 1. National Jewish Health, Denver, CO, USA. 2. University of Michigan, Ann Arbor, MI, USA. 3. Louis Pradel Hospital, Hospices Civils de Lyon, Claude Bernard University Lyon 1, Lyon, France. 4. Department of Medicine, University of Washington, Seattle, WA, USA. 5. Clinical Research Center, National Hospital Organization Kinki-Chuo Chest Medical Center, Osaka, Japan. 6. Department of Pulmonary Medicine and Oncology, Graduate School of Medicine, Nippon Medical School, Tokyo, Japan. 7. Medical University of South Carolina, Charleston, SC, USA. 8. Fondazione Policlinico A. Gemelli, Università Cattolica del Sacro Cuore, Rome, Italy. 9. Boehringer Ingelheim International GmbH, Ingelheim am Rhein, Germany. 10. Boehringer Ingelheim GmbH & Co. KG, Ingelheim am Rhein, Germany. 11. Boehringer Ingelheim Pharmaceuticals, Inc., Ridgefield, CT, USA. 12. National Institute for Health Research Biomedical Research Unit Royal Brompton Hospital, London, UK and Fibrosis Research Group, National Heart and Lung Institute, Imperial College London, UK. 13. National Institute for Health Research Biomedical Research Unit, Royal Brompton and Harefield NHS Foundation Trust, and National Heart and Lung Institute, Imperial College London, UK. Electronic address: rbhild@rbht.nhs.uk.
Abstract
BACKGROUND: In the INPULSIS® trials, nintedanib reduced the annual rate of decline in forced vital capacity (FVC) versus placebo, consistent with slowing of disease progression. We characterised the effects of nintedanib on physiologic outcomes using pooled data from the INPULSIS® trials. METHODS: Post-hoc analyses included changes in FVC over time, cumulative distribution of patients by change in FVC % predicted, and annual rate of decline in FVC in subgroups by diffusing capacity of the lung for carbon monoxide (DLco) and composite physiologic index (CPI) at baseline. Changes from baseline in DLco and oxygen saturation by pulse oximetry (SpO2) were pre-specified. RESULTS:Nintedanib significantly reduced FVC decline versus placebo from week 12. A higher proportion of patients treated with nintedanib than placebo had an improvement or no decline in FVC % predicted, whereas a smaller proportion had absolute declines in FVC ≥5% or ≥10% predicted from baseline to week 52. The effect of nintedanib on FVC decline was similar in patients with baseline DLco >40% versus ≤40% predicted or CPI ≤45 versus >45. There were no significant differences between nintedanib and placebo in change from baseline in DLco % predicted, CPI, or SpO2 at week 52. However, change (deterioration) in CPI was significantly lower with nintedanib versus placebo in patients with CPI > 45 at baseline (1.0 versus 2.9) and CPI >55 at baseline (-1.2 versus 3.3). CONCLUSIONS: A range of physiologic outcome measures in the INPULSIS® trials support the effect of nintedanib on reducing disease progression in patients with IPF.
RCT Entities:
BACKGROUND: In the INPULSIS® trials, nintedanib reduced the annual rate of decline in forced vital capacity (FVC) versus placebo, consistent with slowing of disease progression. We characterised the effects of nintedanib on physiologic outcomes using pooled data from the INPULSIS® trials. METHODS: Post-hoc analyses included changes in FVC over time, cumulative distribution of patients by change in FVC % predicted, and annual rate of decline in FVC in subgroups by diffusing capacity of the lung for carbon monoxide (DLco) and composite physiologic index (CPI) at baseline. Changes from baseline in DLco and oxygen saturation by pulse oximetry (SpO2) were pre-specified. RESULTS:Nintedanib significantly reduced FVC decline versus placebo from week 12. A higher proportion of patients treated with nintedanib than placebo had an improvement or no decline in FVC % predicted, whereas a smaller proportion had absolute declines in FVC ≥5% or ≥10% predicted from baseline to week 52. The effect of nintedanib on FVC decline was similar in patients with baseline DLco >40% versus ≤40% predicted or CPI ≤45 versus >45. There were no significant differences between nintedanib and placebo in change from baseline in DLco % predicted, CPI, or SpO2 at week 52. However, change (deterioration) in CPI was significantly lower with nintedanib versus placebo in patients with CPI > 45 at baseline (1.0 versus 2.9) and CPI >55 at baseline (-1.2 versus 3.3). CONCLUSIONS: A range of physiologic outcome measures in the INPULSIS® trials support the effect of nintedanib on reducing disease progression in patients with IPF.
Authors: U Muscha Steckelings; Robert E Widdop; Edward D Sturrock; Lizelle Lubbe; Tahir Hussain; Elena Kaschina; Thomas Unger; Anders Hallberg; Robert M Carey; Colin Sumners Journal: Pharmacol Rev Date: 2022-10 Impact factor: 18.923
Authors: Claudia Valenzuela; Sebastiano Emanuele Torrisi; Nicolas Kahn; Manuel Quaresma; Susanne Stowasser; Michael Kreuter Journal: Respir Res Date: 2020-01-06
Authors: Toby M Maher; Maureen D Mayes; Michael Kreuter; Elizabeth R Volkmann; Martin Aringer; Ivan Castellvi; Maurizio Cutolo; Christian Stock; Nils Schoof; Margarida Alves; Ganesh Raghu Journal: Arthritis Rheumatol Date: 2021-03-08 Impact factor: 10.995