The online version of this article (doi:10.1186/s12890-015-0034-y) contains supplementary material, which is available to authorized users.
All authors declare no financial support for the submitted work from anyone other than their employer. KOR has been a member of advisory boards for both Intermune and Boehringer Ingelheim and has received consultancy fees and research travel grants from both companies for advisory board work. All other authors have no relationships with commercial entities that might have an interest in the submitted work.
EL developed the research protocol, assisted in the development of the search strategy, assessed studies for inclusion, extracted data from and quality assessed included studies, synthesised evidence, drafted and edited the final manuscript and is the guarantor for the study. VRC synthesised evidence, developed the NMA model and undertook the NMA, drafted the manuscript. DAS synthesised evidence, developed the NMA model and undertook the NMA, drafted the manuscript. JLC contributed to the development of the research protocol, assessed studies for inclusion, extracted data from and quality assessed included studies, synthesised evidence and drafted the manuscript. AJC contributed to developing the research protocol, extracted data from and quality assessed included studies, synthesised evidence, drafted the manuscript. KMAO drafted the manuscript background, assisted with the interpretation of the evidence, drafted the manuscript. All authors read and approved the final manuscript.
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.
Additional file 1: Table S1. MEDLINE search strategy. Appendix. NMA Model code. Figure S1. FVC categorical (>10% decline). Table S2. Acute exacerbations reported in the included trials. Figure S2. Acute exacerbations. Table S3. All-cause mortality. Figure S3. All-cause mortality. Table S4. Respiratory mortality. Figure S4. Respiratory mortality.12890_2015_34_MOESM1_ESM.docx
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- Comparing new treatments for idiopathic pulmonary fibrosis – a network meta-analysis
Vicky R Copley
David A Scott
Jill L Colquitt
Andrew J Clegg
Katherine MA O’Reilly
- BioMed Central
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