Antifibrotic treatment of idiopathic pulmonary fibrosis

Idiopathic pulmonary fibrosis (IPF) is a chronic, progressive, fibrosing interstitial lung disease of unknown etiology with a poor prognosis. The disease is incurable. The antifibrotic drugs pirfenidone and nintedanib are approved for the drug treatment of IPF. The international and current German IPF guidelines recommend the use of pirfenidone and nintedanib in patients with IPF. Both drugs significantly reduce the annual rate of decline in lung function compared with placebo. Additionally, nintedanib has positive effects on the time to the first adjudicated acute IPF exacerbation and pirfenidone reduces the frequency of nonelective respiratory-related hospitalization in IPF patients. Pirfenidone is associated with gastrointestinal and skin-related adverse events and the most frequent adverse event in patients treated with nintedanib is diarrhea. Treatment with pirfenidone and nintedanib is generally well-tolerated and adverse events are in most cases mild to moderate in severity and reversible. Long-term safety and tolerability have been demonstrated for both drugs. In cases of uncontrollable side effects and/or lack of efficacy a switch from pirfenidone to nintedanib and vice versa is possible. Combination therapy with nintedanib/pirfenidone for treatment of IPF is currently not recommended. Positive study results representing potential future treatment options for IPF patients are available for the following drugs: pamrevlumab, a monoclonal antibody against connective tissue growth factor (CTGF), human recombinant pentraxin 2, a monocyte/macrophage differentiation factor, the autotaxin inhibitor GLPG1690 (Galapagos) and PBI-4050, a synthetic analogue of a medium-chain fatty acid that regulates different antifibrotic signaling pathways via binding to G-protein-coupled receptors.