Idiopathic pulmonary fibrosis (IPF) is the most common and deadliest form of interstitial lung disease (ILD), a group of rare, degenerative lung diseases affecting mainly middle-aged and elderly individuals. IPF is chronically progressive, irreversible, and characterized by lung function loss due to fibrosis, which inhibits the lungs from absorbing oxygen. The 5-year survival rate of IPF is 20% to 40%, with a median survival rate of 2 to 5 years, making IPF more lethal than many other malignancies, including breast, ovarian, and colorectal cancer. Most IPF cases are sporadic, but familial IPF accounts for 5% to 20% of cases. In the United States, IPF incidence increases with age and is higher in men than in women (10.7 vs 7.4 per 100,000 patient years).
Due to its unpredictable, individualized clinical course, IPF is difficult to diagnose, and in primary care is frequently misdiagnosed as chronic obstructive pulmonary disease, asthma, emphysema, bronchitis, heart disease, or other diseases that share the same symptoms. In a US survey of 1583 patients, more than half (54.6%) reported a delay of more than 1 year between onset of breathing difficulty and accurate diagnosis, representing a therapeutic void in which IPF is able to progress unchallenged. It is therefore important that primary care physicians suspect an ILD whenever a middle-aged or elderly patient presents with an enigmatic breathing disorder. These patients should be promptly referred to a pulmonologist, who, working in tandem with an experienced radiologist, can confirm the diagnosis.
The latest international IPF treatment guidelines, last updated in 2011, do not mention pharmacologic treatment, because at the time of their publication, no drug therapy for this disease existed. On October 15, 2014, however, based on the results of the phase 3 ASCEND trial, the Food and Drug Administration (FDA) approved pirfenidone for the treatment of IPF, having granted the experimental drug fast-track, priority review, orphan product, and breakthrough designations. Pirfenidone is an orally active, antifibrotic agent that inhibits synthesis of transforming growth factor (TGF)–β, a mediator of cell proliferation and differentiation functions that play a key role in fibrosis. Pirfenidone also inhibits the synthesis of tumor necrosis factor (TNF)–α, an inflammatory cytokine. In the ASCEND trial, 16.5% of the pirfenidone group versus 31.8% of the placebo group demonstrated a clinically meaningful decline in lung function as measured by forced vital capacity (FVC), representing a 48% reduction in the proportion of patients who experienced meaningful changes in FVC, or death.
Also on October 15, 2014, FDA approval of nintedanib, an orally active tyrosine kinase inhibitor, was announced for the treatment of IPF based on the findings of one phase 2 trial (TOMORROW) and two phase 3 trials (INPULSIS™-1 and INPULSIS™-2). Granted breakthrough therapy designation during review, nintedanib inhibits the platelet-derived
growth factor receptor (PDGFR), fibroblast growth factor receptor (FGFR), and vascular endothelial growth factor receptor (VEGFR). Phase 3 clinical trial data indicate that nintedanib reduced the annual rate of decline of lung function by approximately 50%, as measured by FVC over 1 year. According to company news releases, nintedanib is currently available.
Contributed by William Yarnall, RPh, CCP
Medical Writer, Connexion Healthcare