Comparing new treatments for idiopathic pulmonary fibrosis – a network meta-analysis
What this study found
Pirfenidone and nintedanib both reduced the decline in forced vital capacity versus placebo, while NAC showed no consistent benefit. In pirfenidone trials, FVC decline was smaller than placebo in several studies, including King 2014 Ascend (-0.122 vs -0.262 L, P=0.001) and Azuma 2005 (-0.03 vs -0.13 L, P=0.037); nintedanib also showed clear benefit in INPULSIS-1 and INPULSIS-2, with smaller FVC declines than placebo (both P<0.001). Indirect comparisons suggested nintedanib was more effective than pirfenidone at slowing FVC decline. Mortality findings were not consistently significant, but…
- Study & population
- This was a network meta-analysis of randomized trials in adults with idiopathic pulmonary fibrosis, generally with mild to moderate disease and baseline features typical of clinical practice.
- Intervention
- Active regimens evaluated in randomized trials included pirfenidone 1800 to 2403 mg/day orally for 39 to 72 weeks, nintedanib 300 mg/day orally for 52 weeks, and N-acetylcysteine (NAC) given as inhaled NAC, NAC triple therapy, or NAC alone with study-specific doses not reported in the source packet.
- Key limitation
- The network relied on indirect comparisons across trials with different doses, durations, and patient populations, which limits certainty.
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Open PDFOriginal abstract
BackgroundThe 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.MethodsWe 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.ResultsOf 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.ConclusionsTwo 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.