A Cochrane review (abstract , review ) included 15 studies (involving 10 different drugs) with a total of 3 033 subjects. Interferon gamma-1beta did not significantly improve survival compared with placebo (HR 0.88, 95% CI 0.47 to 1.64; statistical heterogeneity I2=65%; 2 studies, n=1 156). Pirfenidone significantly reduced the risk of disease progression by 30% compared with placebo (HR 0.70, 95% CI 0.56 to 0.88; 3 studies, n=1 046). Forced vital capacity or vital capacity was significantly improved by pirfenidone (MD 0.08 L, 95% CI 0.03 to 0.13; 2 studies, n=314).
Other agents were evaluated in single studies. One study compared prednisolone alone with a combination of cyclophosphamide and low-dose prednisolone. Time until failure of the first treatment regimen or time to death was significantly longer for the patients allocated to the treatment arm (P < 0.05) as well as survival, although this was not statistically significant. Azathioprine was utilised in one study; survival was not significantly different between the two groups (P = 0.16), but when the analysis was adjusted for age, there was a significant difference favouring azathioprine (P = 0.02) at up to nine years follow up. Colchicine was studied in one trial; there was a trend towards increased survival in the treatment arm, although this difference did not achieve statistical significance. In one study, N-acetylcysteine slowed the deterioration of vital capacity at 12 months. The overall survival did not differ between the arms. A single study on anticoagulant therapy showed a significant difference in survival between the two study groups in favour of the treatment arm (HR 0.34, 95% CI 0.12 to 0.97). Etanercept did not affect the reduction in disease progression as compared to placebo (HR 0.61, 95% CI 0.32 to 1.17; 1 study). A single study using imatinib failed to demonstrate differences between the imatinib and the placebo group with regard to combined measure of disease progression or death (HR 1.05, 95% CI 0.56 to 1.96). Bosentan was evaluated in one study: a positive trend in favour of bosentan was observed in time to death or disease progression (HR 0.61, 95% CI 0.33 to 1.14).
Comment: The quality of evidence is downgraded by study quality (unclear allocation concealment) and by imprecise results (few patients and wide confidence intervals).