Efficacy and safety of nintedanib in a Greek multicentre idiopathic pulmonary fibrosis registry: a retrospective, observational, cohort study

Abstract

Nintedanib is a tyrosine kinase inhibitor approved for the treatment of idiopathic pulmonary fibrosis (IPF). In a retrospective, real-world study across seven Greek hospitals, we evaluated the effectiveness and safety of nintedanib in routine clinical practice. Patients diagnosed with IPF, as per guideline criteria or multidisciplinary diagnosis, received nintedanib between January 2013 and January 2018.We evaluated 244 patients: mean±sd age 71.8±7.5 years, 79.1% male, 45.1% current smokers and 33.1% ex-smokers at treatment initiation. At baseline, predicted forced vital capacity (FVC) was 73.3±20.7% and predicted diffusing capacity of the lungs for carbon monoxide (DLCO) was 42.6±16.7%. On average, patients spent 23.6±15.0 months on nintedanib. At 3 years, 78 patients had died, equating to a 3-year survival rate of 59.4% (unaffected by treatment discontinuation or dose reduction). FVC% pred and DLCO% pred were largely stable at 3 years, with no significant difference from baseline (FVC 73.3±20.7% pred versus 78±20.1% pred, p=0.074; DLCO 42.6±16.7% pred versus 40.4±18.1% pred, p=0.334). Of the 244 patients, 55.7% reported an adverse event. Gastrointestinal events were the most common (173 (77.2%) out of 224 total events) and 45.0% of patients experienced diarrhoea. Only 32 (13.1%) patients had to permanently discontinue nintedanib due to an adverse event.This real-world study shows a 3-year survival rate of 59.4% and a low discontinuation rate due to adverse events. Our experience is consistent with previous findings in clinical trials of nintedanib in IPF.

Safety of Nintedanib in Patients with Idiopathic Pulmonary Fibrosis: Global Pharmacovigilance Data

“…On the basis of global pharmacovigilance data collected over 4 years, the safety profile of nintedanib in patients with IPF was consistent with that observed in clinical trials, with no new safety concerns observed. The most frequent adverse event reported in the global pharmacovigilance database was non-serious diarrhea, in line with observations from clinical trials [5,[11][12][13][14], observational studies conducted in clinical practice [15][16][17][18][19][20][21][22][23], and post-marketing surveillance data collected in the USA in the year following the approval of nintedanib as a treatment for IPF [24]. Nintedanib is an intracellular inhibitor of tyrosine kinases that inhibits processes fundamental to the pathogenesis of pulmonary fibrosis [9,10,25,26].…”

Pulmonary fibrosis in the aftermath of the Covid-19 era (Review)

“…Trials are based on drugs that are already approved for other diseases, have acceptable safety profiles or have been effective in animal studies against the other two highly pathogenic coronaviruses (30). Pirfenidone and nintedanib are the two approved antifibrotic drugs that, despite having different modes of action, are both effective in attenuating the rate of lung function decline and are widely considered to improve life expectancy (31,32). Apart from the potent use of antivirals to reduce the viral effects, the use of antifibrotic therapies could also be under consideration based on the pulmonary fibrotic disease observed after COVID-19 recovery (33).…”

A real world retrospective observational study exploring the effectiveness and safety of antifibrotics in idiopathic pulmonary fibrosis

“…Many real world studies have been carried out since the licensing of these medications, which have shown the disease stabilising effect of these drugs through sequential FVC measurements [9][10][11][12][13][14]. These studies have also assessed anti brotic tolerability with the discontinuation rate for pirfenidone approximately 29% and for nintedanib between 11% and 19% [9,10,13,14].…”