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Nintedanib in patients with idiopathic pulmonary fibrosis: Combined evidence from the TOMORROW and INPULSIS® trials

Nintedanib in patients with idiopathic pulmonary fibrosis: Combined evidence from the TOMORROW and INPULSIS® trials
Nintedanib in patients with idiopathic pulmonary fibrosis: Combined evidence from the TOMORROW and INPULSIS® trials

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.

Acute exacerbations, Disease progression, Forced vital capacity, Mortality, Quality of life
0954-6111
74-79
Richeldi, Luca
47177d9c-731a-49a1-9cc6-4ac8f6bbbf26
Cottin, Vincent
e73bdd1a-00d4-4cd2-9a0b-a796c361ca84
du Bois, Roland M.
5f8aef36-d70e-4902-aded-f6da129c0741
Selman, Moisés
42c44609-778c-4180-9ffc-fa913a68fbf8
Kimura, Toshio
5d98217e-0c4b-4cac-957a-1a5736fc3e75
Bailes, Zelie
e756870d-7b41-4807-8265-cdf63abe3b7d
Schlenker-Herceg, Rozsa
b99d9236-8d93-43d8-8111-fa21b1f31e0b
Stowasser, Susanne
db03e3f9-5df8-403d-b6f7-5284a506fd94
Brown, Kevin K.
17b83729-65f4-49f7-8347-5f126b15f924
Richeldi, Luca
47177d9c-731a-49a1-9cc6-4ac8f6bbbf26
Cottin, Vincent
e73bdd1a-00d4-4cd2-9a0b-a796c361ca84
du Bois, Roland M.
5f8aef36-d70e-4902-aded-f6da129c0741
Selman, Moisés
42c44609-778c-4180-9ffc-fa913a68fbf8
Kimura, Toshio
5d98217e-0c4b-4cac-957a-1a5736fc3e75
Bailes, Zelie
e756870d-7b41-4807-8265-cdf63abe3b7d
Schlenker-Herceg, Rozsa
b99d9236-8d93-43d8-8111-fa21b1f31e0b
Stowasser, Susanne
db03e3f9-5df8-403d-b6f7-5284a506fd94
Brown, Kevin K.
17b83729-65f4-49f7-8347-5f126b15f924

Richeldi, Luca, Cottin, Vincent, du Bois, Roland M., Selman, Moisés, Kimura, Toshio, Bailes, Zelie, Schlenker-Herceg, Rozsa, Stowasser, Susanne and Brown, Kevin K. (2016) Nintedanib in patients with idiopathic pulmonary fibrosis: Combined evidence from the TOMORROW and INPULSIS® trials. Respiratory Medicine, 113, 74-79. (doi:10.1016/j.rmed.2016.02.001).

Record type: Article

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.

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Accepted/In Press date: 1 February 2016
e-pub ahead of print date: 3 February 2016
Published date: 1 April 2016
Keywords: Acute exacerbations, Disease progression, Forced vital capacity, Mortality, Quality of life

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Local EPrints ID: 443355
URI: http://eprints.soton.ac.uk/id/eprint/443355
ISSN: 0954-6111
PURE UUID: 3a0ab21a-fed4-46c1-8842-9ec3c669e2bf

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Date deposited: 21 Aug 2020 16:30
Last modified: 16 Mar 2021 17:41

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