A Real-Life Multicenter National Study on Nintedanib in Severe Idiopathic Pulmonary Fibrosis

Abstract

Background: Two therapeutic options are currently available for patients with mild-to-moderate idiopathic pulmonary fibrosis (IPF): pirfenidone and nintedanib. To date, there is still insufficient data on the efficacy of these 2 agents in patients with more severe disease. Objectives: This national, multicenter, retrospective real-life study was intended to determine the impact of nintedanib on the treatment of patients with severe IPF. Methods: All patients included had severe IPF and had to have at least 6 months of follow-up before and at least 6 months of follow-up after starting nintedanib. The aim of the study was to compare the decline in lung function before and after treatment. Patient survival after 6 months of therapy with nintedanib was assessed. Results: Forty-one patients with a forced vital capacity (FVC) ≤50% and/or a diffusing capacity of the lung for carbon monoxide (D_LCO) ≤35% predicted at the start of nintedanib treatment were enrolled. At the 6-month follow-up, the decline of D_LCO (both absolute and % predicted) was significantly reduced compared to the pretreatment period (absolute D_LCO at the –6-month, T₀, and +6-month time points (5.48, 4.50, and 5.03 mmol/min/kPa, respectively, p = 0.03; D_LCO% predicted was 32.73, 26.54, and 29.23%, respectively, p = 0.04). No significant beneficial effect was observed in the other functional parameters analyzed. The 1-year survival in this population was 79%, calculated from month 6 of therapy with nintedanib. Conclusions: This nationwide multicenter experience in patients with severe IPF shows that nintedanib slows down the rate of decline of absolute and % predicted D_LCO but does not have significant impact on FVC or other lung parameters.

Guidelines of the Polish Respiratory Society for Diagnosis and Treatment of Idiopathic Pulmonary Fibrosis

“…Data on the efficacy and safety of antifibrotic agents in IPF patients with severe lung function impairment (FVC < 50% of predicted, T L,CO < 30% of predicted) are indeed limited. Nevertheless, an increasing body of evidence from observational studies using antifibrotic agents in this patient population indicates they have similar efficacy and adverse reaction profiles as those observed in pre-marketing randomised clinical trials [253,[258][259][260][261][262][263]. This data supports antifibrotic treatment in IPF patients outside the range of pulmonary function parameters that was used in the inclusion criteria of randomised studies assessing the use of pirfenidone and nintedanib in IPF.…”

Efficacy and safety of nintedanib in patients with advanced idiopathic pulmonary fibrosis

“…Previous analyses of data from the INPULSIS trials have shown that nintedanib has a consistent effect in reducing FVC decline in subgroups of patients with baseline DLco ≤40% versus > 40% predicted [12] and FVC ≤70% versus [14]. A growing body of observational evidence collected in clinical practice suggests that nintedanib is efficacious in reducing disease progression in patients with severe lung function impairment [15][16][17][18][19]. Taken together, these findings support the use of nintedanib in patients with IPF who have advanced disease.…”

Contemporary Concise Review 2018: Interstitial lung disease

“…The strategy must consider an early treatment with the two antifibrotics: pirfenidone or nintedanib. Nowadays, real‐life data about safety and functional stabilization are fully available for both drugs . Particular caution should be taken when the antifibrotic therapy is started because the current dose adjustment guidance is not considering patient’s size and weight: one retrospective study showed that pirfenidone, adjusted for body surface area (BSA) or body weight (BW), had significantly higher doses when an adverse effect was identified.…”