Do Antifibrotics Reduce Mortality, Exacerbations in Idiopathic Pulmonary Fibrosis?

Idiopathic Pulmonary Fibrosis
Idiopathic Pulmonary Fibrosis
A systematic review examined the effect of nintedanib and pirfenidone therapy on mortality and acute exacerbations in idiopathic pulmonary fibrosis.

Antifibrotic therapy seems to reduce the risk of all-cause mortality and acute exacerbations in patients with idiopathic pulmonary fibrosis (IPF), according to research findings published in Chest.

In the study, a small research team conducted a systematic literature review and subsequent meta-analysis to determine the effects of antifibrotic treatment on all-cause mortality and acute exacerbations in a large cohort of patients with IPF.

The review and meta-analysis included 8 randomized controlled studies and 18 cohort studies that compared mortality or acute exacerbation events in 12,956 patients (75% male) with IPF who were treated with antifibrotics (n=6425) vs those not treated with antifibrotics (n=6531).

Follow-up durations across studies ranged between 9 months and 120 months. Medications used were pirfenidone and nintedanib, but some studies’ medications were unspecified.

Treatment with antifibrotic agents was associated with a reduced risk of all-cause mortality in the pooled analysis (relative risk [RR], 0.55; 95% CI, 0.45-0.66; I2=82%). In a sensitivity analysis which removed studies that reported only hazard ratios, the pooled RR remained significant for reduced all-cause mortality with antifibrotic treatment (RR, 0.58; 95% CI, 0.46-0.73; I2=85%).

In the meta-analysis focused on acute exacerbations, the researchers analyzed data from 7 studies involving 2002 treated and 1323 nontreated patients with IPF. Treatment with antifibrotics was also associated with a reduced risk of acute exacerbations in this analysis (RR, 0.63; 95% CI, 0.53-0.76; I2=0%). Treatment effect on risk was consistent in a subgroup analysis focused on only nintedanib use (RR, 0.62; 95% CI, 0.43-0.89; I2=0%).

The researchers noted that it was not possible to evaluate the effects of antifibrotic therapies in certain subgroups, such as patients with preserved lung volume or severe disease. Additionally, the investigators stated that the pooled analysis of cohort studies may have resulted in high heterogeneity.

While antifibrotic therapy seems to reduce all-cause mortality risk and acute exacerbations in patients with IPF, the investigators added that other “considerations unable to be accounted for in this meta-analysis include baseline disease severity and comorbidities.” They explained that these data “remain relevant to real-world practice in terms of determining long-term risks and benefit of antifibrotic treatment.”


Petnak T, Lertjitbanjong P, Thongprayoon C, Moua T. Impact of antifibrotic therapy on mortality and acute exacerbation in idiopathic pulmonary fibrosis: A systematic review and meta-analysis. Chest. 2021;160(5):1751-1763. doi:10.1016/j.chest.2021.06.049