Safety assessment of switching from fingolimod to siponimod: An Italian multicenter prospective study

Introduction: Safety concerns have been raised regarding fingolimod to siponimod transition in people with Secondary Progressive Multiple Sclerosis (SPMS). Objective: To explore factors associated with the choice of switching from fingolimod to siponimod and the safety of this sequencing. Methods: We conducted a prospective observational study that included patients who had a confirmed diagnosis of SPMS at the time of study entry and had been treated with fingolimod for at least two years. Upon enrollment, patients either continued fingolimod (comparator group) or transitioned to siponimod (switch group) and were followed up for six months to assess disease activity and changes in laboratory parameters. Results: Out of 95 SPMS subjects, 42 (44.2 %) switched to siponimod at study entry. The switch group was younger and had more prior treatments than the comparator group (p = 0.042 and p = 0.015, respectively). Five subjects experienced disease activity (three in the switch group, two in the comparator). Patients switching to siponimod experienced a greater increase in GPT (p = 0.015) and GOT levels (p = 0.041) at 6 months. Four adverse events were reported: melanoma and grade IV lymphopenia in the comparator group, and grade IV lymphopenia and dizziness in the switch group. Conclusion: During the 6-month observation period, switching from fingolimod to siponimod was safe in terms of disease reactivation and tolerability.