Neutrophil-to-Lymphocyte Ratio Predicts Infusion-Site Skin Nodules in Parkinson’s Disease Patients Receiving Foslevodopa/Foscarbidopa Subcutaneous Infusion

Abstract Background Continuous subcutaneous foslevodopa/foscarbidopa infusion (LDp/CDp-CSI) is an effective treatment for patients with Parkinson’s disease (PD), but infusion-site nodules are a major cause of treatment discontinuation. Systemic inflammation can influence local skin tolerance; however, predictive biomarkers remain unidentified. Objective To evaluate the predictive value of the neutrophil-to-lymphocyte ratio (NLR) for clinically significant infusion-site nodules (PD-CSN) during LDp/CDp-CSI and to establish a clinical management framework to mitigate their development. Methods We prospectively followed 38 patients with PD initiating LDp/CDp-CSI for ≥3 months. Baseline immunological data were collected before infusion. A subset of 30 patients was followed for an average of 11 months to identify factors associated with skin nodules at longer follow-up. Nodules were classified by blinded raters. Between-group comparisons, ANCOVA, ROC curve, and Kaplan-Meier analyses were performed. Results At 3 months, 42% of patients were PD-CSN and showed higher baseline neutrophil counts ( P =0.030) and NLR ( P =0.007), with NLR remaining independently associated with nodule status (F=7.06, P =0.012). ROC analysis demonstrated acceptable discrimination (AUC=0.73, P =0.016). At last follow-up, lower baseline lymphocyte counts ( P =0.002) and higher NLR ( P =0.001) were observed in PD-CSN. High baseline NLR predicted earlier nodule onset ( P =0.001). Despite frequent nodules, multidisciplinary team surveillance, including remote and in-person follow-up, limited treatment discontinuation to 5.3%. Conclusions Baseline systemic inflammation, reflected by NLR, predicts both the onset and persistence of infusion-site nodules during LDp/CDp-CSI. NLR may serve as a clinically accessible biomarker for early risk stratification. Multidisciplinary surveillance facilitates timely nodule management and enhances treatment adherence.