There has been one phase 4 trial that has investigated the combination of Ofev (nintedanib) and Esbriet (pirfenidone) for idiopathic pulmonary fibrosis (IPF) that showed a slightly increased risk of side effects with combination treatment, but the trial was not large enough to make a solid conclusion about increased/decreased effectiveness. Both Ofev and Esbriet slow IPF’s worsening, but do not stop its progression, and neither medication is recommended over the other. Because they work on different aspects of the fibrotic cascade, there has been some suggestion that there may be benefit in combining them.
This phase 4 trial showed an increased risk of gastrointestinal side effects with the combination, with diarrhea, nausea, and/or vomiting reported in 37 out of 53 patients (70%), compared to just 27 out of 51 patients (53%) given nintedanib alone. However, there was less decline in FVC over 12 weeks in patients treated with nintedanib and add-on pirfenidone than with nintedanib alone. The authors noted that the trial was not powered for this endpoint and was not long enough to draw conclusions about the efficacy of combination treatment and larger and longer trials are needed. There was no overall change in the quality of life between the two combinations and plasma trough concentrations of nintedanib were similar when it was administered alone or with add-on pirfenidone.
2022 guidelines issued by the American Thoracic Society in collaboration with the European Respiratory Society, Japanese Respiratory Society, and the Asociación Latinoamericana de Tórax, give no preference for nintedanib monotherapy over pirfenidone monotherapy and do not give a recommendation about using the two in combination. For non-IPF progressive pulmonary fibrosis, the guidelines recommend:
- More research on the efficacy, effectiveness, and safety of pirfenidone in patients with non-IPF progressive pulmonary fibrosis and also in patients with specific types of ILD that manifest progressive pulmonary fibrosis.
- Nintedanib (Ofev) is recommended for the treatment of progressive pulmonary fibrosis in patients who failed standard management.