Real-world safety profiles of pirfenidone and nintedanib in idiopathic pulmonary fibrosis patients

Dorine Fournier (1, 2) , Stéphane Jouneau (3, 1) , Guillaume Bouzillé (4, 1) , Elisabeth Polard (1, 3) , Marie-Noëlle Osmont (2) , Lucie-Marie Scailteux (1, 3)

1 Centre Hospitalier Universitaire de Rennes [CHU Rennes] = Rennes University Hospital [Ponchaillou]
2 CRPV - Centre Régional de Pharmacovigilance [Rennes]
3 Irset - Institut de recherche en santé, environnement et travail
4 LTSI - Laboratoire Traitement du Signal et de l'Image

Introduction: While pirfenidone and nintedanib have greatly influenced the treatment of idiopathic pulmonary fibrosis (IPF), both drugs have significant early adverse drug reactions (ADRs) and almost nothing is known of their rare and delayed ADRs. We collected and analyzed pirfenidone- or nintedanib-related ADRs identified in a French rare lung disease center, recorded their profiles and identified potential safety signals.Methods: We analyzed the medical records of IPF patients treated with pirfenidone or nintedanib between January 2011 and January 2020 at the Rennes University Hospital to estimate the incidence of serious and non-serious ADRs cases due to each drug and the incidence of ADRs involving the cardiovascular, hepatobiliary, gastro-intestinal, dermatological, and metabolic/nutritional systems.Results: The 176 patients included 115 (65%) initially treated with pirfenidone and 61 (35%) given nintedanib. ADRs occurred in 78.3% of those given pirfenidone and in 70.5% of those given nintedanib. The incidence of first serious ADRs cases was about 33 per 100 person-years (100 PY) for both drugs; first non-serious pirfenidone ADRs cases were 102 per 100 PY and 130 per 100 PY for nintedanib. The incidence involving each organ system were quite similar, except for the gastro-intestinal and skin disorders. Cardiovascular disorders occurred in about 10 cases per 100 PY in both pirfenidone and nintedanib patients.Discussion: Most ADRs were consistent with the expected antifibrotic drug safety profiles. As arterial and venous thromboembolic events are rare, it is important to assess the risk associated with using antifibrotics by a dedicated pharmacoepidemiological study.

Mots clés: Adverse drug reaction; Idiopathic pulmonary fibrosis; Nintedanib; Pirfenidone; Safety profile

Domaines: Pharmacologie

Dorine Fournier, Stéphane Jouneau, Guillaume Bouzillé, Elisabeth Polard, Marie-Noëlle Osmont, et al.. Real-world safety profiles of pirfenidone and nintedanib in idiopathic pulmonary fibrosis patients. Pulmonary Pharmacology and Therapeutics, 2022, 76, pp.102149. ⟨10.1016/j.pupt.2022.102149⟩. ⟨hal-03954444⟩