Relapse presentation in relapsing multiple sclerosis (RMS) differs between sexes, leading to differential outcomes. An influence of age seems likely but is less well investigated separately for women and men. Using the large well-defined dataset of the pivotal trials of ocrelizumab in RMS, OPERA I and II, and their open-label extension, we performed a post hoc analysis to investigate relapse phenotypes for sex- and age-related differences in n = 929 relapses in 534 subjects (171 men, 363 women). Frequencies of affected functional systems were analyzed separated by sex and for three age strata (<35, 35-44, ≥45 years). Exact p-values are given for this exploratory analysis. Frequencies of mono- versus polysymptomatic relapse presentations were different neither between sexes nor in different age groups. Cerebellar symptoms were more frequent in relapses in men (female [f]: 23.1%, male [m]: 33.0%, p = 0.002), and women's relapses included more sensory (f: 53.8%, m: 32.3%, p < 0.001) and fatigue symptoms (f: 22.6%, m: 14.7%, p = 0.006). Whereas the sex difference for sensory involvement was present over all age groups (<35 years: f: 58.3%, m: 30.4%, p < 0.001; 35-44 years: f: 53.7%, m: 36.0%, p = 0.003; ≥45 years: f: 47.8%, m: 28.8%, p = 0.009), the difference for cerebellar involvement diminished with age (<35 years: f: 20.1%, m: 33.3%, p = 0.009; 35-44 years: f: 22.7%, m: 34.2%, p = 0.034; ≥45 years: f: 27.8%, m: 30.3%, p = 0.750). Relapse presentation seemed to shift with age in women only. We describe sex-specific relapse presentations and an influence of age only for women. Underlying causal factors warrant further investigations.
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