From the Guidelines
OFEV (nintedanib) and ESBRIET (pirfenidone) are medications used to treat idiopathic pulmonary fibrosis (IPF), a progressive lung disease, by slowing the progression of IPF through different mechanisms, with OFEV inhibiting multiple tyrosine kinases and growth factor receptors, and ESBRIET acting as an anti-fibrotic and anti-inflammatory agent. The mechanism of action of OFEV involves inhibiting multiple tyrosine kinases and growth factor receptors involved in fibrosis, including platelet-derived growth factor, fibroblast growth factor, and vascular endothelial growth factor, as seen in the INPULSIS-1 and INPULSIS-2 trials 1. By blocking these pathways, OFEV reduces the activity of fibroblasts, which are cells that produce excessive collagen and contribute to scarring in the lungs. ESBRIET works through a different mechanism, acting as an anti-fibrotic and anti-inflammatory agent, reducing the production of inflammatory cytokines and growth factors while inhibiting collagen synthesis and fibroblast proliferation, as supported by the updated guidelines for the treatment of IPF 1. Some key points to consider when using these medications include:
- OFEV is typically taken at a dose of 150mg twice daily
- ESBRIET is usually titrated to 801mg three times daily
- Common side effects of OFEV include gastrointestinal issues, such as diarrhea and nausea, as reported in the INPULSIS trials 1
- Common side effects of ESBRIET include photosensitivity and gastrointestinal problems, as noted in the guidelines for the treatment of IPF 1
- Neither medication should be abruptly discontinued, and patients should work closely with their healthcare provider to manage side effects and monitor treatment effectiveness, as emphasized in the guidelines for the treatment of IPF 1. It is essential to consider the individual patient's preferences and the potential benefits and risks of treatment when making decisions about the use of OFEV and ESBRIET, as highlighted in the European Respiratory Review 1.
From the FDA Drug Label
12.1 Mechanism of Action The mechanism of action of pirfenidone in the treatment of IPF has not been established.
The FDA drug label does not answer the question.
From the Research
Mechanism of Action
- OFEV (nintedanib) and ESBRIET (pirfenidone) are antifibrotic medications used to treat idiopathic pulmonary fibrosis (IPF) 2, 3.
- Nintedanib works by slowing the annual rate of decline in forced vital capacity (FVC) in patients with IPF, thereby reducing the progression of the disease 4.
- Pirfenidone has been shown to reduce disease progression compared to placebo, with a statistically significant reduction in all-cause mortality observed when pooling data across studies 5.
Efficacy and Safety
- Both nintedanib and pirfenidone have been demonstrated to be effective and well-tolerated treatments for IPF, with common side effects including gastrointestinal issues 2, 4.
- The adoption of these medications in real-world practice has been low, potentially due to high out-of-pocket costs 6.
- Nintedanib and pirfenidone have similar treatment effects, but with slightly different adverse event profiles 5.
Treatment Outcomes
- Nintedanib has been shown to slow IPF disease progression by reducing the rate of decline in FVC, with potential reductions in mortality and acute exacerbations in certain subgroups of patients 4.
- Pirfenidone has been found to be effective in reducing disease progression compared to best supportive care (BSC) or nintedanib, although there is uncertainty in the cost-effectiveness estimates due to factors such as treatment duration and stopping rules 5.