Pharmacotherapy and adjunctive treatment for idiopathic pulmonary fibrosis (IPF)

Idiopathic pulmonary fibrosis (IPF) is an advancing and fatal lung disease with increasing incidence and prevalence. Nintedanib and pirfenidone were approved by the FDA for the treatment of IPF in 2014 based on positive phase 3 trials, and both of these antifibrotic drugs are conditionally recommended in the 2015 ATS/ERS/JRS/ALAT Clinical Practice Guideline. Although an improvement over previously suggested therapies, their capacity to reduce, but not completely arrest or improve, lung function over time presents an opportunity for novel or add-on pharmacologic agents. The purpose of this review is to deliver a brief overview of the results of phase 3/4 IPF trials with pirfenidone and nintedanib, as well as highlight encouraging results of phase 1/2 trials with novel therapies. Long-term studies indicate that pirfenidone and nintedanib are effective IPF treatments, with acceptable safety and tolerability. The combination of pirfenidone and nintedanib appear safe. Promising results have recently been made public for several phase 2 trials with novel targets, including the autotaxin-lysophosphatidic acid (ATX/LPA) pathway, connective tissue growth factor (CTGF), pentraxin-2, G protein-coupled receptor agonists/antagonists, alpha v beta 6 integrin, and galectin-3. Results of treatments directed at gastro-esophageal reflux in patients with IPF have also been published. Currently, monotherapy with pirfenidone or nintedanib is the mainstay of pharmacological treatment for IPF. Innovative therapies along with combinations of pharmacological agents hold great promise for the future.