Comment on: Neutrophil-to-lymphocyte ratio as a biomarker for disease onset and mortality risk in systemic sclerosis: a real-world national cohort study: reply

Dear Edıtor, We thank Dr Chen et al. [1] for their interest in our recently published work and for the opportunity to clarify several methodological aspects regarding our study, ‘Neutrophil-to-Lymphocyte Ratio as a Biomarker for Disease Onset and Mortality Risk in Systemic Sclerosis: A Real-World National Cohort Study’ [2]. With respect to variable selection in the multivariable Cox regression model, in the submitted manuscript, we focused on the robust multivariable results in order to emphasize established and clinically relevant predictors of mortality in SSc. To enhance transparency, we provide in Table 1 both the univariate and multivariable Cox regression analyses. As shown, the hazard ratios for the neutrophil-to-lymphocyte ratio (NLR) categories are highly consistent between the two models, supporting the stability and independent prognostic value of NLR. Notably, NLR values of 3.00–3.99 and ≥4.0 demonstrated significant associations with mortality in both analyses. Regarding the concern about potential confounding by immunosuppressive therapy at the time of baseline NLR measurement, only 21 of the 1511 patients, representing 1.4% of the cohort, were treated with any immunosuppressant, including MTX, MMF, rituximab, or IVIG, at the time of baseline NLR evaluation. None of the patients were treated with other biologic therapies such as tocilizumab. Given this very low exposure rate, baseline immunosuppressive treatment is highly unlikely to have influenced the overall results or the observed association between NLR and mortality.