Efficacy and safety of nintedanib in patients with advanced idiopathic pulmonary fibrosis

Luca Richeldi,Birgit Schinzel,Susanne Stowasser,Martin Kolb,Wim A Wuyts,Manuel Quaresma,Stéphane Jouneau,Ganesh Raghu

doi:10.1186/s12890-019-1030-4

Abstract

BackgroundThe two 52-week INPULSIS trials investigated nintedanib versus placebo in patients with IPF, FVC ≥50% predicted and DLco 30–79% predicted. The 24-week INSTAGE trial investigated nintedanib plus sildenafil versus nintedanib alone in patients with IPF and DLco ≤35% predicted. We used data from INPULSIS and INSTAGE to compare the effects of nintedanib in patients with IPF with less versus more severe impairment in gas exchange at baseline.MethodsAnalyses were conducted in patients treated with nintedanib alone in the INPULSIS and INSTAGE trials and in patients treated with placebo in the INPULSIS trials. Outcomes included the rate of decline in FVC over 24 weeks, the proportions of patients who had a confirmed or suspected idiopathic acute exacerbation over 24 weeks, deaths over 24 weeks, and adverse events. Analyses were descriptive.ResultsIn total, 638 and 136 patients received nintedanib alone in the INPULSIS and INSTAGE trials, respectively, and 423 patients received placebo in the INPULSIS trials. Rates of FVC decline were − 52.3 and − 66.7 mL/24 weeks in patients treated with nintedanib alone in INPULSIS and INSTAGE, respectively, and − 102.8 mL/24 weeks in patients treated with placebo in INPULSIS. Confirmed or suspected idiopathic acute exacerbations were reported in 0.6 and 3.7% of patients treated with nintedanib alone in INPULSIS and INSTAGE, respectively, and 2.1% of patients treated with placebo in INPULSIS. Deaths occurred in 2.0, 11.0 and 1.9% of patients in these groups, respectively. Diarrhoea adverse events were reported in 52.5 and 48.5% of patients treated with nintedanib alone in INPULSIS and INSTAGE, respectively, and 16.1% of patients treated with placebo in INPULSIS.ConclusionsBased on data from the INSTAGE and INPULSIS trials, nintedanib had a similar effect on FVC decline over 24 weeks, and a similar safety and tolerability profile, in patients with IPF and more versus less severe impairment in gas exchange. These data support the use of nintedanib in patients with IPF who have advanced disease.Trial registrationINPULSIS (NCT01335464 and NCT01335477); INSTAGE (NCT02802345).

Highlights

The two 52-week INPULSIS trials investigated nintedanib versus placebo in patients with Idiopathic pulmonary fibrosis (IPF), forced vital capacity (FVC) ≥50% predicted and DLco 30–79% predicted
In the two 52-week INPULSIS trials, nintedanib reduced the annual rate of decline in forced vital capacity (FVC) by approximately 50% compared with placebo in patients with IPF and mild or moderate impairment in lung function at baseline, with an adverse event profile predominantly characterised by gastrointestinal events [6]
We investigated changes from baseline in FVC and St. George’s Respiratory Questionnaire (SGRQ) total score at weeks 12 and 24; the rate of decline in FVC over 24 weeks; and the proportions of patients who had an absolute decline in FVC ≥5% predicted or died, had an adjudicated confirmed or suspected idiopathic acute exacerbation, or who died from any cause over 24 weeks in patients who received nintedanib alone in the INPULSIS and INSTAGE trials and in patients who received placebo in the INPULSIS trials

Summary

Introduction

The two 52-week INPULSIS trials investigated nintedanib versus placebo in patients with IPF, FVC ≥50% predicted and DLco 30–79% predicted. We used data from INPULSIS and INSTAGE to compare the effects of nintedanib in patients with IPF with less versus more severe impairment in gas exchange at baseline. In the two 52-week INPULSIS trials, nintedanib reduced the annual rate of decline in forced vital capacity (FVC) (mL/year) by approximately 50% compared with placebo in patients with IPF and mild or moderate impairment in lung function at baseline, with an adverse event profile predominantly characterised by gastrointestinal events [6]. In the 24week INSTAGE trial, nintedanib plus sildenafil was associated with a numerical but not statistically significant benefit on change in St. George’s Respiratory Questionnaire (SGRQ) total score compared with nintedanib alone in patients with IPF and severely impaired gas exchange (diffusing capacity of the lungs for carbon monoxide [DLco] ≤35% predicted) at baseline [7]

Methods

Results

Conclusion