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

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. The review compared pirfenidone, nintedanib, and NAC against placebo and against each other for lung function and other outcomes.

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. Comparators were placebo in the included trials.

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 trends sometimes favored pirfenidone; evidence for quality of life was limited.

The network relied on indirect comparisons across trials with different doses, durations, and patient populations, which limits certainty. Several studies had short follow-up, and evidence for mortality and quality of life was sparse or inconsistent. Some included trials had unclear risk of bias, and the review mixes data across pirfenidone, nintedanib, and NAC rather than one uniform intervention.