A comparison of natalizumab and ocrelizumab on disease progression in multiple sclerosis

objective: no direct comparisons of the effect of natalizumab and ocrelizumab on progression independent of relapse activity (PIRA) and relapse-associated worsening (RAW) events are currently available. we aimed to compare the risk of achieving first 6 months confirmed PIRA and RAW events and irreversible expanded disability status scale (EDSS) 4.0 and 6.0 in a cohort of naïve patients treated with natalizumab or ocrelizumab from the Italian multiple sclerosis register. methods: patients with a first visit within 1 year from onset, treated with natalizumab or ocrelizumab, and ≥3 visits were extracted. pairwise propensity score-matched analyses were performed. risk of reaching the first PIRA, RAW, and EDSS 4.0 and 6.0 events were estimated using multivariable cox proportional hazards models. kaplan–meier curves were used to show cumulative probabilities of reaching outcomes. wresults: In total, 770 subjects were included (natalizumab = 568; ocrelizumab = 212) and the propensity score-matching retrieved 195 pairs. no RAW events were found in natalizumab group and only 1 was reported in ocrelizumab group. a first PIRA event was reached by 23 natalizumab and 25 ocrelizumab exposed patients; 7 natalizumab- and 10 ocrelizumab-treated patients obtained an irreversible EDSS 4.0, while 13 natalizumab- and 15 ocrelizumab-treated patients reached an irreversible EDSS 6.0. no differences between the two groups were found in the risk (HR, 95%CI) of reaching a first PIRA (1.04, 0.59–1.84; p = 0.88) event, an irreversible EDSS 4.0 (1.23, 0.57–2.66; p = 0.60) and 6.0 (0.93, 0.32–2.68; p = 0.89). Interpretation: both medications strongly suppress RAW events and, in the short term, the risk of achieving PIRA events, EDSS 4.0 and 6.0 milestones is not significantly different.