Switching to ozanimod as a strategy to adjust fingolimod-related lymphopenia

Introduction: Fingolimod is a disease-modifying therapy for multiple sclerosis (MS) that modulates sphingosine 1-phospate receptors, impeding the egress of lymphocytes from lymphnodes and thus causing lymphopenia. Severe lymphopenia should lead to fingolimod discontinuation. We aim to evaluate whether switching from fingolimod to ozanimod can adjust fingolimod-related lymphopenia while maintaining clinical efficacy. Methods: In this real-world observational study, we included 18 people with MS (47.7 ± 7.6 years of age, 77.8 % of women, 13.9 ± 6.9 years of disease duration, median EDSS 3.0) at the time of fingolimod discontinuation due to lymphopenia. We collected laboratory (lymphocyte absolute count on the same hematological counter) and clinical variables at fingolimod discontinuation, at ozanimod prescription, and 6 months after ozanimod prescription. Results: From 13 cases of grade 3 and 4 lymphopenia at the time of fingolimod discontinuation, we observed only 2 cases of grade 3 and no cases of grade 4 lymphopenia after 6 months of ozanimod treatment. On paired t-tests, absolute lymphocyte count at fingolimod discontinuation were lower than ozanimod prescription (p<0.001), and after 6 months (p<0.001). We observed no clinical changes. Discussion: People with MS who have severe fingolimod-related lymphopenia and are clinically stable, can exhibit increased absolute lymphocyte counts when switched to ozanimod, while preserving clinical stability.