Two antifibrotic agents, nintedanib and pirfenidone, significantly reduced all-cause mortality among people with idiopathic pulmonary fibrosis (IPF) or non-IPF progressive lung fibrosis, according to findings published online in BMC Pulmonary Medicine.

However, there was no significant difference between the 2 patient groups in the power of either medication to prevent a decline in forced vital capacity (FVC) (P =.979), This finding suggested a common pathogenetic origin of IPF and non-IPF progressive lung fibrosis.

Investigators conducted a systematic review and meta-analysis which identified 13 randomized controlled trials published between 1990 and July of 2021. The final analysis included 11 trials that documented the effects of nintedanib or pirfenidone on all-cause mortality or changes in FVC in adults with IPF or non-IPF progressive lung fibrosis.

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When the investigators analyzed the effects of antifibrotics on all-cause mortality, they calculated an overall mean risk ratio of 0.701 (P =0.008). This indicated that antifibrotics significantly reduced mortality when the groups were considered together.

The researchers also analyzed the effects of antifibrotics within each patient group, calculating estimated risk ratios of 0.637 (P =.004) for the IPF studies and 0.908 (P =.71) for the non-IPF studies. Therefore, antifibrotic agents did not significantly reduce mortality when considering only individuals with non-IPF conditions.

The investigators analyzed the effect of antifibrotic agents on the rate of FVC decline within the IPF and non-IPF groups, calculating mean effect sizes of -0.305 and -0.307, respectively (P <.001).

Study limitations included the differing number of patients on nintedanib (n=494) and pirfenidone (n=153) in the non-IPF trials as well as the differing methods of data analysis in the FVC studies. These required the authors to use standardized differences. “Different approaches to imputation of data . . . [complicated] interpretation of the scale of effects,” the authors wrote.

Another limitation was the use of all-cause mortality as a primary outcome measure. This impacted the interpretation of the efficacy of antifibrotic agents in preventing disease-related mortality.

Two investigators found 3 of the 11 studies had “some concerns” of bias in 1 of 5 domains. They rated the remaining studies as having a low risk of bias in all 5 domains.


Finnerty JP, Ponnuswamy A, Dutta P, Abdelaziz A, Kamil H. Efficacy of antifibrotic drugs, nintedanib and pirfenidone, in treatment of progressive pulmonary fibrosis in both idiopathic pulmonary fibrosis (IPF) and non-IPF: a systematic review and meta-analysis. BMC Pulm Med. 2021;21(1):411. doi:10.1186/s12890-021-01783-1