This study summary is an excerpt from the book 2 Minute Medicine’s The Classics in Medicine: Summaries of the Landmark Trials
1. In this report of two randomized, placebo-controlled trials, nintedanib reduced force vital capacity decline in patients with idiopathic pulmonary fibrosis versus control over 52 weeks.
2. Nintedanib was relatively safe, with its most frequent adverse event being diarrhea.
Original Date of Publication: May 2014
Study Rundown: The INPULSIS 1 and 2 trials sought to evaluate the efficacy of nintedanib, an intracellular tyrosine kinase inhibitor, in the treatment of idiopathic pulmonary fibrosis. Overall, the rate of decline of forced vital capacity (FVC), a surrogate for disease progression, was significantly reduced in those receiving nintedanib (P < 0.001 in both trials). The INPULSIS-2 trial additionally found a significant increase in the time to first disease exacerbation in the treatment group (P = 0.005), however INPULSIS-1 did not. Diarrhea was the most frequently reported adverse event in both groups, usually mild to moderate in intensity, leading to discontinuation for less than 5% of participants in both trials. The rate of serious adverse events did not differ significantly versus placebo for both trials. Although this is a well-designed trial offering convincing support for the use of nintedanib in idiopathic pulmonary fibrosis, it has several limitations. It failed to show a clear effect of nintedanib on improved time to first acute exacerbation of disease, an important endpoint given its high association with morbidity and mortality.
In-Depth [randomized control trial]: The INPULSIS-1 and 2 trials randomized 1066 and 515 patients, respectively, between May 2011 and September 2012 at 205 sites internationally. All patients were 40 years or older with a diagnosis of idiopathic pulmonary fibrosis in the past 5 years. Patients were randomized to receive either 150mg of nintedanib twice daily or placebo for a total of 52 weeks, with spirometric testing for FVC performed periodically during this period. Overall, the adjusted annual decline in FVC was significantly reduced in the treatment group for both trials (P < 0.001 for both). Time to first acute exacerbation was similar between treatment groups for INPULSIS-1 (P = 0.67), however was significantly lower in the nintedanib group for INPULSIS-2 (P = 0.005). There was no significant difference in deaths from any cause in either trial. Over 90% of patients in both trials reported mild to moderate diarrhea when using nintedanib. Serious adverse events did not differ significantly between groups.
Richeldi L, du Bois RM, Raghu G, Azuma A, Brown KK, Costabel U, et al. Efficacy and Safety of Nintedanib in Idiopathic Pulmonary Fibrosis. New England Journal of Medicine. 2014 May 29;370(22):2071–82.
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