Safety of nintedanib added to pirfenidone treatment for idiopathic pulmonary fibrosis

Abstract

We assessed safety and tolerability of treatment with pirfenidone (1602-2403 mg day-1) and nintedanib (200-300 mg day-1) in patients with idiopathic pulmonary fibrosis (IPF). This 24-week, single-arm, open-label, phase IV study (ClinicalTrials.gov identifier NCT02598193) enrolled patients with IPF with forced vital capacity % pred ≫50% and diffusing capacity of the lung for carbon monoxide % pred ≫30%. Before initiating nintedanib, patients had received pirfenidone for ≫16 weeks and tolerated a stable dose of ≫1602 mg day-1 for ≫28 days. The primary end-point was the proportion of patients who completed 24 weeks of combination treatment on pirfenidone (1602- 2403 mg day-1) and nintedanib (200-300 mg day-1). Investigators recorded treatment-emergent adverse events (TEAEs), attributing them to pirfenidone, nintedanib, both or neither. 89 patients were enrolled; 73 completed 24 weeks of treatment (69 meeting the primary end-point) and 16 discontinued treatment prematurely (13 due to TEAEs). 74 patients had 418 treatment-related TEAEs, of which diarrhoea, nausea and vomiting were the most common. Two patients had serious treatmentrelated TEAEs. Combined pirfenidone and nintedanib use for 24 weeks was tolerated by the majority of patients with IPF and associated with a similar pattern of TEAEs expected for either treatment alone. These results encourage further study of combination treatment with pirfenidone and nintedanib in patients with IPF.