The aim of the study is to analyze relapse phenotypes during the first disease modifying therapy and to characterize any association with worst disease course in terms of disability accrual.

The impact of each relapse phenotype on disease course, in terms of disability accrual and disease modifying therapies (DMTs) discontinuation remain the least explored in a real world setting.

A multicenter, observational, retrospectively acquired cohort was utilized for the current study. Anonymized clinical data of patients with RRMS were extracted from the Italian MS Register from their first treatment prescription with DMT (between January 1, 2010 and December 31, 2019) to their last follow-up with the same treatment. We collected retrospectively all  relapses after the starting of the prescribed DMT.

Out of more than 11,000 patients, a total of 3,012 matched the inclusion criteria. The mean age at onset was 31.8±10.7, out of them 230 (32.4%) were male. Baseline Expanded Disability Status Scale (EDSS) was 2.0 (1.5-2.5). Based on the phenotypes, 567/766 patients (74%) had a first mono-symptomatic relapse and 199 patients (26%) poly-symptomatic one. Considering only patients with poly-symptomatic relapse, the most frequent phenotypes involved sensory functions (42%). The Visual function phenotype occurs in over 70% as a mono phenotype. Whether having had a relapse does not have a significant effect on the probability of having an EDSS≥4.0 (HR = 1.14, CI95% 0.79-1.65). Among patients who have had relapses there were no differences between mono and poly symptomatic ones (HRpolivsmono = 1.07, CI95% 0.54-2.13). Pyramidal phenotype was associated with an increased risk of having an EDSS within 5 years greater than or equal to 4 (HR = 3.36, 95% CI 1.78-6.35; p <0.001). 

 Specific phenotypes of relapses in RRMS patients and temporal shifts between phenotypes according to relapse type, progression and the role of each DMT need further investigation.