Baseline neutrophil-to-lymphocyte ratio predicts survival time after the initiation of nintedanib in patients with interstitial lung disease

BACKGROUND: The neutrophil-to-lymphocyte ratio (NLR) is a marker of systemic inflammation, with prognostic value in interstitial lung disease (ILD). However, the association between baseline NLR and the therapeutic efficacy of nintedanib remains unclear. This study investigates the relationship between baseline NLR values and clinical outcomes in patients with idiopathic pulmonary fibrosis (IPF) and progressive fibrosing-ILD (non-IPF ILD) receiving nintedanib therapy. METHODS: This retrospective multicenter study included 406 patients-169 with IPF and 237 with non-IPF ILD-who initiated nintedanib treatment between 2019 and 2023 across 15 institutions in Japan. Patients were stratified into low- and high-NLR groups using a cutoff of 2.86. Comparative analysis assessed survival time, forced vital capacity (FVC) changes, and acute exacerbations. RESULTS: The high-NLR group demonstrated shorter median survival time in the overall study population (1,171 vs. 1,386 days; p =0.025). In subgroup analyses, higher NLRs were associated with shorter survival time in patients with IPF (778 vs. 1,447 days; p =0.006), but not in the non-IPF ILD group. While nintedanib mitigated FVC decline in most subgroups, this effect was attenuated in patients with IPF and high-NLR, with no statistically significant benefit (-8.63% vs. -6.71%). In multivariable analysis, NLR was not found to be an independent predictor of the annual relative FVC decline in any group. The incidence of acute exacerbations did not differ significantly between groups. CONCLUSIONS: While baseline NLR did not independently predict the annual relative FVC decline, it was identified as a significant independent predictor of survival time in patients with ILD, particularly those with IPF, following the initiation of nintedanib.