Efficacy and Safety of Nintedanib in Idiopathic Pulmonary Fibrosis, Cytisine versus Nicotine for Smoking Cessation, and FACED Score for Non-Cystic Fibrosis Bronchiectasis

摘要

Idiopathic pulmonary fibrosis (IPF) is chronic, and ultimately fatal, lung scarring of unknown etiology characterized by dyspnea and progressive loss of lung function. Nintedanib is an intracellular inhibitor of various tyrosine kinases shown in a phase 2 trial to decrease the rate of decline of FVC in IPF (2). The INPULSIS study group conducted two replicate phase 3 trials (INPULSIS-1 and INPULSIS-2) to determine the efficacy and safety of nintedanib (150 mg twice daily) in patients with IPF. These trials were multinational, randomized, double-blind, placebo-controlled, parallel-group studies. Patients (1,066) were randomized in a 3:2 fashion (309 nintedanib and 204 placebo in INPULSIS-1; 329 nintedanib and 219 placebo in INPULSIS-2) to receive either nintedanib or placebo for 52 weeks. Inclusion criteria included the following: patient age, at least 40 years; high-resolution computed tomography (HRCT) within the previous 12 months; a diagnosis of IPF within the past 5 years, confirmed centrally by a single radiologist and single pathologist who reviewed the HRCT images (all patients) and lung biopsies (if available); FVC not exceeding 50% predicted, and diffusing capacity of the lung for carbon monoxide (Dl_(CO)) of 30-79% predicted. The primary end point was decline in FVC over 12 months, and secondary end points included time to first IPF exacerbation and change in the St. George's Respiratory Questionnaire (SGRQ) score over 12 months.