Efficacy and safety of combination therapy with pirfenidone and nintedanib in patients with idiopathic pulmonary fibrosis

Jin-Young Huh; Jae Ha Lee; Jin Woo Song

doi:10.3389/fphar.2023.1301923

Efficacy and safety of combination therapy with pirfenidone and nintedanib in patients with idiopathic pulmonary fibrosis

Front Pharmacol. 2023 Dec 12:14:1301923. doi: 10.3389/fphar.2023.1301923. eCollection 2023.

Authors

Jin-Young Huh^{1

2}, Jae Ha Lee³, Jin Woo Song¹

Affiliations

¹ Department of Pulmonary and Critical Care Medicine, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea.
² Division of Pulmonary, Allergy and Critical Care Medicine, Department of Internal Medicine, Chung-Ang University Gwangmeyong Hospital, Chung-Ang University College of Medicine, Gwangmyeong, Republic of Korea.
³ Division of Pulmonology and Critical Care Medicine, Department of Internal Medicine, Inje University Haeundae Paik Hospital, Inje University College of Medicine, Busan, Republic of Korea.

Abstract

Background: Recent studies have suggested that combination therapy with pirfenidone and nintedanib is safe and tolerable in patients with idiopathic pulmonary fibrosis (IPF). However, data from real-world practice are limited. Thus, we aimed to investigate the safety and efficacy of this combination therapy in patients with IPF in a real-world setting. Methods: A multicenter retrospective cohort study was conducted to investigate the safety and efficacy of combination therapy with pirfenidone and nintedanib in 45 patients with IPF. Incidences of adverse events and rates of lung function decline were compared before and after the combination therapy. Propensity score matching was performed to compare the outcomes between the combination and monotherapy groups. Results: The mean age of the patients was 68.8 years, and 82.2% of them were male. The median follow-up duration after combination therapy was 12.1 months. The majority of the patients (97.8%) received nintedanib as an add-on to pirfenidone. The most common adverse events after the combination therapy were diarrhea and anorexia. Pirfenidone or nintedanib was stopped in 12 patients owing to gastrointestinal AEs, lung transplantation, or financial problems. In patients with serial lung function data, the rate of decline in the forced vital capacity was significantly reduced after the combination therapy. In the matched analysis, the combination group had a higher incidence of diarrhea than the monotherapy group without an increase in serious adverse events; however, the two groups had similar changes in forced vital capacity (FVC). Conclusion: The combination of pirfenidone and nintedanib in patients with IPF has the potential to reduce the rate of FVC decline. However, in the matched analysis, FVC decline was comparable between the patients on combination therapy and those on monotherapy. The incidence of certain adverse events, particularly diarrhea, was higher with combination therapy, but serious adverse events were similar between the groups.

Keywords: antifibrotic agents; combination therapy; idiopathic pulmonary fibrosis; nintedanib; pirfenidone.

Grants and funding

The author(s) declare financial support was received for the research, authorship, and/or publication of this article. This study was supported by grants from the Basic Science Research Program (NRF-2022R1A2B5B02001602) and the Bio & Medical Technology Development Program (NRF-2022M3A9E4082647) of the National Research Foundation of Korea (NRF) funded by the Ministry of Science & ICT, Republic of Korea. This study was also supported by the National Institute of Health research project (2021ER120701) and the Korean Environment Industry & Technology Institute via the Core Technology Development Project for Environmental Diseases Prevention and Management Program funded by the Korean Ministry of Environment (RS-2022-KE002197), Republic of Korea.