Background: The association between treatment-related lymphopenia in multiple sclerosis, drug efficacy and the risk of infections is not yet fully understood.
Objective: The objective of this study was to assess whether lymphopenia is associated with short-term treatment response and infection rate in a real-life multiple sclerosis population treated with fingolimod and dimethyl-fumarate. We assessed the associations between baseline absolute lymphocyte count and the lymphocyte mean percentage decrease at 6 and 12 months with treatment response and the occurrence of adverse events over 12 months in the entire cohort of patients and in the two treatment groups separately.
Methods: This is a retrospective observational real-world study of patients with multiple sclerosis treated with fingolimod and dimethyl-fumarate at the MS Center of the University of Genoa between 2011 and 2018. Patients with at least 12 months of follow-up were eligible if [1] they had an Expanded Disability Status Scale assessment at baseline and 12 months after treatment onset, [2] they had undergone brain magnetic resonance imaging at baseline and after 12 months, and [3] absolute lymphocyte counts were available at baseline, 6 and 12 months. Patients shifting from dimethyl-fumarate to fingolimod or vice versa were excluded from the analysis.
Results: In total, 137 and 75 patients treated with fingolimod and dimethyl-fumarate, respectively, were included in the analysis. At 12 months, fingolimod-treated patients were more likely to experience grade II and grade III lymphopenia compared with dimethyl-fumarate patients (p < 0.001, χ2 = 94) and had a higher lymphocyte mean percentage decrease (p < 0.001, U = 540). A higher number of previous therapies and a lower baseline absolute lymphocyte count were predictors of lymphopenia at 6 months (p = 0.047, odds ratio = 1.60 and p = 0.014, odds ratio = 1.1) and 12 months (p = 0.003, odds ratio = 1.97 and p = 0.023, odds ratio = 1.1). In fingolimod-treated patients only, female sex and a higher Expanded Disability Status Scale score were predictors of lymphopenia at 12 months (p = 0.006, odds ratio = 7.58 and p = 0.03, odds ratio = 1.56). Neither absolute lymphocyte count at 6 and 12 months nor the mean percentage decrease at 6 and 12 months predicted No Evidence of Disease Activity (NEDA-3) status at 1 year, the occurrence of relapses, disease activity on MRI or disability progression.
Conclusions: Our findings suggest that peripheral blood lymphocyte changes are not associated with short-term treatment response and with the rate of infections during fingolimod and dimethyl-fumarate treatment in real-world patients. Higher treatment exposure and a lower baseline absolute lymphocyte count are risk factors for lymphopenia development during fingolimod and dimethyl-fumarate therapy.