Comparison of the clinical effectiveness of nintedanib at full and reduced dosage in patients with idiopathic pulmonary fibrosis and progressive non-idiopathic fibrosis

<bold>Background:</bold> Nintedanib has demonstrated to reduce disease progression and mortality in patients with idiopathic pulmonary fibrosis (IPF) and progressive pulmonary fibrosis (PPF): a reduced dosage is available for tolerability purposes but its clinical effectiveness is yet to be fully clarified. <bold>Aims and Objectives:</bold> to compare the effectiveness of nintedanib at full and reduced dosage in a cohort of patients with IPF and PPF. <bold>Methods:</bold> we retrospectively collected the demographic, clinical and respiratory functional data of 345 patients (268 with IPF and 77 with PPF) treated with nintedanib and followed in our Centre from 2015 to 2022. Outcome analysis was focused on all-cause mortality and disease progression expressed as a FVC decline rate > 10%/year. <bold>Results:</bold> overall, the reduction of dosage was necessary in 132 patients due to safety or tolerability reasons. The outcome analysis showed no differences of mortality and functional decline between patients treated with full or reduced dose of nintedanib (p=0.202 and p=0.564, respectively): a worse survival was observed in patients treated on compassionate grounds due to severe FVC or DLCO reduction at baseline (p=0.0006). Multivariate Cox regression analysis identified male sex (HR 3.48 [1.52-7.95]) a baseline FVC% < 70% (HR 1.25 [1.04-1.38]) and the compassionate treatment regimen (HR 6.4 [2.1-9.6]) as the factors associated with a worse survival. <bold>Conclusions:</bold> our findings suggest that a reduction of dosage of nintedanib is not associated with worse outcomes and may represent a feasible option for patients unable to tolerate a full-dose treatment regimen.