Management of Progressive Disease in Idiopathic Pulmonary Fibrosis

Idiopathic pulmonary fibrosis (IPF) is a prototype of chronic, progressive, and fibrotic lung disease. It has been considered rare, with an incidence estimated to 11.5 cases per 100 000 individuals per year. Increasing rates of hospital admissions and deaths due to IPF suggest an increasing burden of disease. The median survival time from diagnosis is 2-4 years. Recently two disease-modifying therapies, pirfenidone and nintedanib, have been approved worldwide. Both drugs reduce the disease progression as measured by progressive decline in forced vital capacity (FVC), with a reduction of overall mortality showed by meta-analysis of phase III pirfenidone trials. However, progression of disease continues to occur despite the currently available drug therapy. Many patients die from progressive, chronic hypoxemic respiratory failure, or less frequently from acute exacerbation of pulmonary fibrosis. In these patients, no data are available to guide management between continuation of the prescribed antifibrotic drug, to switch to the other available antifibrotic drug, or to combine the available drugs. The combination of nintedanib and pirfenidone is not recommended outside clinical trials. However, although both antifibrotic drugs were developed and approved as monotherapy, two recent trials have suggested the feasibility and safety of combining them over a 12-24 weeks period. These results encourage further studies of combination treatment with pirfenidone and nintedanib in patients with IPF. Such study is timely, as there is a risk that clinicians facing the continued worsening of disease in patients receiving one of the available drugs may prescribe both drugs combined outside clinical trials, potentially exposing patients to a currently unknown risk. This study will evaluate the efficacy and tolerance of the combination pirfenidone and nintedanib as compared to a "switch monotherapy": i.e. switching from the current to the other of the two existing drugs prescribe