From the Guidelines
The combined use of Ofev (nintedanib) and Esbriet (pirfenidone) for idiopathic pulmonary fibrosis (IPF) is not currently recommended as standard therapy due to limited evidence supporting safety and efficacy, and the potential for increased adverse effects. These medications are both approved as monotherapies for idiopathic pulmonary fibrosis, but using them together has limited evidence supporting their combined use. The combination could potentially increase the risk of adverse effects, particularly gastrointestinal issues like nausea, diarrhea, and liver enzyme elevations, as both drugs have overlapping side effect profiles [ 1 ]. Each medication works through different mechanisms to slow disease progression - nintedanib inhibits tyrosine kinases involved in fibrosis pathways while pirfenidone has anti-inflammatory and antifibrotic properties [ 1 ].
Key Considerations
- Clinical trials have not established clear benefits of combination therapy that outweigh the increased risk of side effects and cost.
- Patients should discuss with their pulmonologist which single agent might be most appropriate based on their specific clinical situation, comorbidities, and tolerance profile rather than pursuing combination therapy outside of clinical trial settings.
- The potential for adverse effects, such as photosensitivity, fatigue, stomach discomfort, and anorexia, is increased with pirfenidone treatment [ 1 ].
- Nintedanib treatment has been associated with a lower percentage of patients with more than 10% FVC decline during the 12-month follow-up period, but also with more adverse events and serious adverse events [ 1 ].
Recommendations
- Monotherapy with either Ofev (nintedanib) or Esbriet (pirfenidone) is recommended for the treatment of IPF, based on individual patient needs and tolerance.
- Combination therapy should only be considered in the context of clinical trials or after careful discussion with a pulmonologist, weighing the potential benefits and risks.
From the Research
Efficacy of Combining Ofev (Nintedanib) and Esbriet (Pirfenidone)
- The combination of pirfenidone and nintedanib has the potential to reduce the rate of forced vital capacity (FVC) decline in patients with idiopathic pulmonary fibrosis (IPF) 2.
- A study found that the rate of decline in FVC was significantly reduced after the combination therapy, although in the matched analysis, FVC decline was comparable between the patients on combination therapy and those on monotherapy 2.
- Another study showed that nintedanib with add-on pirfenidone had a manageable safety and tolerability profile in patients with IPF, with a mean change from baseline in FVC at Week 12 of -13.3 ml, compared to -40.9 ml in patients treated with nintedanib alone 3.
Safety of Combining Ofev (Nintedanib) and Esbriet (Pirfenidone)
- The most common adverse events after the combination therapy were diarrhea and anorexia, with pirfenidone or nintedanib stopped in 12 patients due to gastrointestinal adverse events, lung transplantation, or financial problems 2.
- The incidence of certain adverse events, particularly diarrhea, was higher with combination therapy, but serious adverse events were similar between the groups 2.
- A study found that combined pirfenidone and nintedanib use for 24 weeks was tolerated by the majority of patients with IPF, with a similar pattern of treatment-emergent adverse events expected for either treatment alone 4.
- Nintedanib is well tolerated and has been shown to be safe for up to 51 months, with gastrointestinal events, mainly diarrhea, being the main adverse events caused by the treatment 5.
Overall Assessment
- The available evidence suggests that the combination of nintedanib and pirfenidone is safe and effective in reducing the rate of FVC decline in patients with IPF, although the incidence of certain adverse events is higher with combination therapy 2, 3, 4.
- Further research is needed to fully understand the efficacy and safety of combining Ofev (nintedanib) and Esbriet (pirfenidone) in the treatment of IPF 3, 6.