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Idiopathic Pulmonary Fibrosis Treatment Option
San Diego—Idiopathic pulmonary fibrosis (IPF) is an interstitial lung disease in which the tissue in the lungs hardens causing a progressive decline in lung function. IPF typically occurs in Caucasian males ≥50 years of age who have a history of smoking cigarettes.
“Unfortunately, the lung does not know how to repair itself so if we do not institute drugs that will stop the process, this is a terrible cascade with a pathway of destruction and an average life span of 3.8 years,” said Marilyn K. Glassberg, MD, professor, medicine and surgery, and director, rare and interstitial lung disease program, Miller School of Medicine, University of Miami, at the AMCP meeting during a science and innovation theater. The event was sponsored by Boehringer Ingelheim Pharmaceuticals, Inc. There are only 2 FDA-approved drugs to treat IPF; Dr. Glass- berg reviewed 1 of them—nintedanib, a kinase inhibitor. The recommended dose is 150 mg twice a day (approximately 12 hours apart) taken with food.
Clinical Trials
Nintedanib was assessed in 3 randomized, double-blind, placebo-controlled trials, which included 1231 patients; 723 were randomized to receive nintedanib and 508 were randomized to receive placebo. To qualify for the study, participants had to be ≥40 years of age and had a diagnosis of IPF <5 years with a predicted forced vital capacity (FVC) mL/year of ≥50%. FVC is the amount of air that can be forcibly exhaled from the lungs.
The primary end point of the studies was the annual rate of decline in FVC mL/ year. Secondary end points included the time to first acute exacerbation, change from baseline in FVC percent predicted, and survival.
Study 1, Study 2, and Study 3 demonstrated a relative reduction in FVC compared to placebo by 52%, 45%, and 68%, respectively. Risk of time to acute IPF exacerbation was significantly reduced in 2 of the 3 studies; Study 2 demonstrated an 80% relative reduction and Study 3 demonstrated an 84% relative reduction. These results indicated that nintedanib slowed the progression of IPF, reduced the decline in lung function, and reduced the risk to the first acute exacerbation. Dr. Glassberg noted, “There is no effect on morality [with nintedanib].”
Adverse Events
The most common adverse reaction to nintedanib in participants across all studies was diarrhea (62%) compared to the placebo (18%). “When the drug is dispensed by the specialty pharmacy, it is included to have loperamide with it and it is very important that patients are instructed on rehydration and management of diarrhea,” said Dr. Glassberg.
Other common adverse reactions to nintedanib compared to placebo included nausea (24% vs 7%, respectively), abdominal pain (15% vs 6%, respec- tively), and liver enzyme elevation (14% vs 3%, respectively). Elevated levels of liver enzymes can be reversed with dose reduction. In the event of an adverse reac- tion, nintedanib doses can be reduced to 100 mg or discontinued completely. Of the participants receiving nintedanib, 16% reported adverse events that lead to a permanent dose reduction, while 21% of those who received nintedanib reported discontinuing the drug completely.
Arterial thromboembolic events were reported in 2.5% of participants who received nintedanib compared to placebo (.8%). Risk of bleeding was also reported in participants randomized to nintedanib (10%) compared to placebo (7%). Gastrointestinal perforation was reported in .3% of participants who received nintedanib compared to placebo (0%).
It is recommended that patients receiving nintedanib be tested for liver function efficiency prior to treatment and every 3 months after beginning treatment.—Melissa D. Cooper
