Safety of nintedanib added to pirfenidone treatment for idiopathic pulmonary fibrosis

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 treatment-related 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.