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Background Comparative effectiveness of natalizumab and fingolimod over a follow-up longer than 2 years has been not addressed yet. Objectives To compare the effect on no evidence of disease activity (NEDA-3) in relapsing-remitting multiple sclerosis (RRMS) patients treated with natalizumab or fingolimod for at least 4 years. Methods We included RRMS patients switched from first-line agents to natalizumab or fingolimod. Patients were propensity score (PS)-matched on a 1-to-1 basis. Percentages of patients reaching NEDA-3 status at 2 and 4 years of follow-up were compared using the chi-square test. The risk of not achieving NEDA-3 at 4 years was explored in matched samples by Cox regression models. Results We evaluated 174 PS-matched patients. Patients receiving natalizumab reached a NEDA-3 status at 2 and 4 years more frequently than those exposed to fingolimod (63% vs 44%, p=0.037; 45.7% vs 25.8%, p=0.015, respectively). Patients receiving natalizumab were at a significant lower risk of not achieving the NEDA-3 status at 4 years compared to those exposed to fingolimod (hazard ratio (95% confidence interval): 0.54 (0.36–0.80), p=0.002). Conclusions Although both medications were effective in patients non-responding to first-line agents, natalizumab seems to be superior to fingolimod in RRMS in obtaining NEDA-3 status at 4 years.

Background Fingolimod (FTY) induces sequestration of lymphocytes in secondary lymphoid organs and the average lymphocyte recovery following discontinuation takes 1-2 months. It has been hypothesized that the therapeutic effects of subsequent cell-depleting agents may be compromised if initiated before lymphocyte recovery has occurred. Objective To assess the risk of relapses following FTY discontinuation and the initiation of a B/T cell-depleting agent in relation to washout duration using data from the Italian MS Register. Methods The risk of relapses was assessed in relation to different washout durations (< 6, 6-11, 12-17 and > / = 18 weeks) in patients starting alemtuzumab, rituximab, ocrelizumab or cladribine following FTY discontinuation. ResultsWe included 329 patients in the analysis (226F, 103 M; mean age 41 ± 10 years). During the cell-depleting treatment, the incidence rate ratio for a relapse was significantly greater in patients with a washout period of 12-17 and > / = 18 weeks compared to the reference period (< 6 weeks). The risk of a relapse was significantly influenced by the occurrence of relapses during FTY treatment and by washout length, with hazard ratios markedly increasing with the washout duration. ConclusionThe risk of relapses increases with the washout duration when switching from FTY to lymphocyte-depleting agents.

Background: Definitions for reliable identification of transition from relapsing-remitting multiple sclerosis (MS) to secondary progressive (SP)MS in clinical cohorts are not available. Objectives: To compare diagnostic performances of two different data-driven SPMS definitions. Methods: Data-driven SPMS definitions based on a version of Lorscheider’s algorithm (DDA) and on the EXPAND trial inclusion criteria were compared, using the neurologist’s definition (ND) as gold standard, in terms of sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), Akaike information criterion (AIC) and area under the curve (AUC). Results: A cohort of 10,240 MS patients with ⩾5 years of follow-up was extracted from the Italian MS Registry; 880 (8.5%) patients were classified as SPMS according to the neurologist definition, 1806 (17.6%) applying the DDA and 1134 (11.0%) with the EXPAND definition. The DDA showed greater discrimination power (AUC: 0.8 vs 0.6) and a higher sensitivity (77.1% vs 38.0%) than the EXPAND definition, with similar specificity (88.0% vs 91.5%). PPV and NPV were higher using the DDA than considering EXPAND definition (37.5% vs 29.5%; 97.6% vs 94.0%). Conclusion: Data-driven definitions demonstrated greater ability to capture SP transition than neurologist’s definition and the global accuracy of DDA seems to be higher than the EXPAND definition.