Comparing new treatments for idiopathic pulmonary fibrosis – a network meta-analysis

Emma Loveman, Vicky R Copley, David A Scott, Jill L Colquitt, Andrew J Clegg, Katherine MA O’Reilly

The treatment landscape for idiopathic pulmonary fibrosis, a devastating lung disease, is changing. To investigate the effectiveness of treatments for idiopathic pulmonary fibrosis we undertook a systematic review, network meta-analysis and indirect comparison. We searched MEDLINE, EMBASE and The Cochrane library for relevant studies. Randomised controlled trials of pirfenidone, nintedanib or N-acetylcysteine were eligible. Predefined processes for selecting references, extracting data and assessing study quality were applied. Our network meta-analysis of published data used a fixed effect model. For forced vital capacity measures a standardised mean difference approach was used and converted to odds ratios for interpretation. Of 1076 references, 67 were retrieved and 11 studies included. Studies were of reasonable size, populations were similar, and the overall quality was good. Only two treatments, pirfenidone (odds ratio 0.62, 95% credible interval 0.52, 0.74) and nintedanib (0.41, 95% credible interval 0.34, 0.51) produced a statistically significant slowing in the rate of forced vital capacity decline compared with placebo. In an indirect comparison, results indicate that nintedanib is statistically significantly better than pirfenidone in slowing forced vital capacity decline (odds ratio 0.67, 95% credible interval 0.51, 0.88). Results were stable in scenario analysis and random effects models. Indirect comparisons of mortality were not statistically significant between nintedanib and pirfenidone. Two treatments show beneficial effects and when compared indirectly nintedanib appears to have superior benefit on forced vital capacity. Limitations to indirect comparisons should be considered when interpreting these results, however, our findings can be useful to inform treatment decisions.