Ricerc@Sapienza

Background: Currently siponimod, an oral selective S1PR1,5 modulator, is indicated for the treatment of adult patients with active SPMS. Data from the phase 3 study showed a significant effect of the active drug compared with placebo on reduction of disability progression. The visual system is an important model to evaluate the pathophysiology of MS and in the last years it is used as a model for studying outcomes in clinical trials evaluating novel neuroprotective drugs in MS. Visual system can be studied using several technologies as Optical coherence tomography (OCT), Visual evoked potentials (VEPs) and Trans bulbar B-mode sonography (TBS).
Objective: To evaluate the effects of siponimod on neurodegeneration and remyelination in progressive MS patients using OCT, PEV and TBS-derived metrics
Methods: 50 patients with active SPMS taking Siponimod in routine clinical practice will be enrolled in this single-center, pilot study. The primary outcome was the change in RNFL thickness from baseline to 12 months to evaluate the possible role as neuroprotective agent of Siponimod. Secondary outcome will be change in P100 latency on full-field visual evoked potential from baseline to 12 months. Moreover, the role of Trans bulbar B-mode sonography as measure of neurodegeneration in MS will be evaluated.
Conclusion: In EXPAND TRIAL Siponimod have demonstrated a relative risk reduction of 21% for confirmed disability progression (CDP) at 3 and 6 months in patients with active secondary progressive (SP) MS compared with placebo. Siponimod could slow down disease progression via routes beyond an anti-inflammatory effect. None have demostrated if the the disability progression reduction is related to a neuroprotective or remyelinating role of Siponimod. The study of visual system using OCT, PEV and TBS might represent innovative, non invasive and cost- effective technologies to analyze neurodegeneration in MS