Antifibrotic Therapy in Idiopathic Pulmonary Fibrosis
Nintedanib and Mortality
- The American Thoracic Society, European Respiratory Society, Japanese Respiratory Society, and Latin American Thoracic Association conditionally recommend nintedanib for IPF treatment based on its ability to slow disease progression, with a relative risk of 0.70 (95% CI 0.47–1.03) for mortality, although this remained statistically non-significant, in patients with IPF 1, 2
- Nintedanib slows FVC decline by approximately 125 ml/year compared to placebo, with a difference of 125.2 ml (95% CI 77.7–172.8), in patients with IPF 1, 2
- Nintedanib reduces the proportion of patients experiencing ≥10% absolute FVC decline, with a relative risk of 1.16 (95% CI 1.06–1.27), in patients with IPF 1, 2
- The INPULSIS-1 and INPULSIS-2 trials showed no significant mortality benefit with nintedanib versus placebo, with a relative risk of 0.70 (95% CI 0.44–1.11) over 52 weeks, in 1,066 patients with IPF 1, 2
Pirfenidone and Mortality
- Pooled analyses from clinical trials suggest a 30% reduction in risk of disease progression, with a hazard ratio of 0.70 (95% CI 0.56–0.88), although this refers to FVC decline, not mortality, in patients with IPF 6
- The American Thoracic Society, European Respiratory Society, Japanese Respiratory Society, and Latin American Thoracic Association conditionally recommend pirfenidone for IPF treatment based on its ability to slow disease progression, in patients with IPF 1, 2
Clinical Implications
- Both nintedanib and pirfenidone slow disease progression by reducing the rate of FVC decline, which is the primary mechanism by which they may extend survival, in patients with IPF 1, 2, 6, 7
- The 2022 updated guidelines extend conditional recommendations for nintedanib to progressive pulmonary fibrosis beyond IPF, based on its ability to slow disease progression, in patients with progressive pulmonary fibrosis 3, 4, 5, 8