Nintedanib Combined With Pirfenidone in Patients With Idiopathic Pulmonary Fibrosis or Progressive Pulmonary Fibrosis: A Long-Term Retrospective Multicentre Study (Combi-PF)

Abstract

Background: Antifibrotic therapy only reduces disease progression in patients with idiopathic pulmonary fibrosis (IPF) or progressive pulmonary fibrosis (PPF), highlighting the need for more effective therapeutic strategies. Whether combining nintedanib and pirfenidone is safe and tolerable in real-world setting is poorly known.

Methods: We conducted a multicentre, retrospective study of patients with IPF or PPF who had received a combination of nintedanib and pirfenidone and primarily assessed safety and tolerability. Secondary objectives included assessment of dose reduction, treatment cessation, survival, and lung function outcomes.

Results: We included 38 patients (84.2% with IPF) who received combination therapy between 2014 and 2024. Adverse drug reactions occurred in 84.2% of patients (severe in 28.9%): weight loss (52.6%), diarrhoea (36.8%), abdominal pain (28.9%). Dose was reduced in 28.9% of patients, and combination was discontinued in 26.3%. Median follow-up was 17.4 months; the median duration of combination therapy was 12.8 months. The rate of decline in FVC decreased from -26.7 before the initiation of the combination to -11.1mL/months during combination therapy. The median survival from diagnosis was 28.5 months, with a 5-yr survival of 21.7%. Among patients listed for lung transplantation, 11 (52.4%) underwent transplantation, of whom 6 had continued the combination until the transplantation.

Conclusion: Although no new safety signal arose, combination therapy is challenging in real-world setting due to poor tolerability especially weight loss. It can nevertheless be a viable treatment option in some patients, particularly as a bridge to lung transplantation. Further studies are needed to confirm the efficacy of this combined therapeutic strategy.

Keywords: Combination therapy; Idiopathic pulmonary fibrosis; Lung transplantation; Nintedanib; Pirfenidone; Progressive pulmonary fibrosis.