Idiopathic pulmonary fibrosis is a form of progressive lung disease which ultimately leads to death. The cause is unknown, but the disease is characterised by scar tissue in the lungs. This prevents the lungs from working effectively. Standard treatment uses oral corticosteroids in association with immunosuppressors, but there is uncertainty as to whether this treatment is effective. Immunosuppressive agents such as azathioprine and cyclophosphamide have been used to treat the disease because it is thought they might prevent inflammation. The review found 15 high quality trials of non-steroid drugs tested in idiopathic pulmonary fibrosis patients. Notwithstanding the encouraging results of a first small study included in the first version of this review, the effects of interferon gamma-1beta, as assessed by combining two subsequent large trials, were disappointing and failed to show an effect on improving survival. Four studies did evaluate pirfenidone, an anti-fibrotic oral drug, on a large number of patients: although two of these studies have only been presented in conferences,combining the published and unpublished data showed a significant improvement of pirfenidone on progression-free survival and a small increase in pulmonary function. Current evidence suggests a possible role for pirfenidone in the treatment of idiopathic pulmonary fibrosis, though data on survival are now needed. However, trials with other non-steroid agents are currently ongoing and new evidence may become available soon.
Based on available data, partly still unpublished, pirfenidone appears to improve progression-free survival and, to a lesser extent, pulmonary function in patients with idiopathic pulmonary fibrosis. More data are needed on overall survival and quality of life on treatment. From the studies in this review, interferon gamma-1beta has not been shown to affect survival. Other agents evaluated in single studies either failed to provide evidence for a benefit or need to be assessed in larger randomised controlled trials.
Idiopathic pulmonary fibrosis is a chronic progressive lung disease with poor outcome and no effective treatment to date. This is an update of a Cochrane Review first published in 2003.
To assess the efficacy of non-steroid agents in adults with idiopathic pulmonary fibrosis.
We searched the Cochrane Airways Group Register (30 March 2010), the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library, Issue 1, 2010), Ovid MEDLINE to March week 5, 2010, EMBASE to week 13, 2010 and PubMed to April 2010, with additional handsearching, including abstracts of international conferences. We also contacted pharmaceutical companies and researchers in the field.
Randomised studies comparing non-steroid drugs with placebo or steroids in adults with idiopathic pulmonary fibrosis.
Two authors independently assessed trial quality, extracted data and assessed risk of bias. We contacted pharmaceutical companies to obtain missing information, if any. We combined survival outcomes using Peto odds ratios or hazard ratios (HR).
Fifteen trials involving 10 different drugs were included. Two trials enrolling 1156 patients compared interferon gamma-1beta with placebo: interferon gamma-1beta did not significantly improve survival (HR 0.88, 95% CI 0.47 to 1.64; P = 0.68). Four trials involving 1155 patients compared pirfenidone with placebo. Three trials, conducted in 1046 patients, provided data on progression-free survival: pirfenidone significantly reduced the risk of disease progression by 30% (HR 0.70, 95% CI 0.56 to 0.88, P = 0.002). Data on the effect of pirfenidone on pulmonary function could only be assessed for two studies analysing 314 patients. Forced vital capacity or vital capacity was significantly improved by pirfenidone (mean difference 0.08 L, 95% CI 0.03 to 0.13, P = 0.0006).