Disease Activity in Early-Stage Relapsing MS Remains Minimal After 4 Years of Ocrelizumab Treatment
After 192 weeks, more than 90% of patients on ocrelizumab had no relapses and slightly more than 80% had no 24-week confirmed disability progression.
New data from the phase 3b ENSEMBLE study (NCT03085810) assessing ocrelizumab (Ocrevus; Genentech) in patients with relapsing-remitting multiple sclerosis (RRMS) showed stable or improved disability progression in most patients treated up to 4 years. Safety results were consistent with the known ocrelizumab safety profile, with no new safety signals.
The analysis included 678 individuals with early-stage RRMS with a disease duration of less than 3 years who received ocrelizumab 600 mg every 24 weeks for 192 weeks. At week 192, 77.9% of patients showed no evidence of clinical activity and 85.0% achieved no evidence of MRI activity. Above all, 66.4% of patients treated with first-line ocrelizumab maintained no evidence of disease activity (NEDA) after 4 years of treatment.
These findings were presented at the
In the trial, patients received ocrelizumab 300 mg intravenously on days 1 and 15 for the first dose, followed by 600 mg IV every 24 weeks for 4 years. At the conclusion of the 4-year period, 90.9% (n = 539) of patients had no relapses, and 81.8% (n = 485) had no 24-week confirmed disability progression (CDP). Furthermore, 90.6% and 90.4% of patients, respectively, showed no T1-weighted contrast enhancing lesions or T2-weighted lesions by the end of the observed period.
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Over a total of 2385 patient-years followed, there were 54 relapses total, equating to an adjusted annualized relapse rate of 0.023 (95% CI, 0.02-0.03). In terms of 24-week CDP, 15.9% (n = 108) of the cohort had an event while the remaining 84.1% (n = 570) did not. At 4 years, 82.1% of those on ocrelizumab had either stable or improved EDSS. More specifically, 22.8% improved, 59.3% remained stable, and 18.0% worsened.
In total, 95.4% (n = 647) of patients experienced an adverse event (AE) throughout the trial, 3.1% (n = 21) of which were grade 3 and above. Serious AEs were recorded by 15.5% (n = 105) of the cohort, and death occurred in 6 patients (0.6%). Fatalities included 2 cases of COVID-19, 2 cases of COVID-19 pneumonia, 1 case of pneumonia, and 1 case of immune reconstitution inflammatory syndrome. Infusion-related reactions, infections, and serious infections were found in 51.8%, 75.2%, and 6.9% of patients, respectively. Of the IRRs (n = 351), none were grade 4 and above, and 13 were grade 3.
Ocrelizumab, an anti-CD20 monoclonal antibody, has been approved for relapsing MS and primary progressive MS. In 2020, the FDA approved a shorter 2-hour infusion time for ocrelizumab based on findings from ENSEMBLE-PLUS, a prospective substudy to the open-label, single-arm, phase 3b ENSEMBLE trial. Findings from ENSEMBLE-PLUS showed a similar frequency and severity of infusion reactions for a 2-hour ocrelizumab infusion time compared to the previously approved 3.5-hour time in patients with RRMS.2
REFERENCE
1. Bermel R, Hatung H, Brochet B, et al. Low disease activity over 4 years of ocrelizumab therapy in treatment-naïve patients with early-stage relapsing-remitting multiple sclerosis: the phase 3b ENSEMBLE study. Presented at: 2023 AAN Annual Meeting; April 22-27; Boston, MA. Abstract 001928
2. FDA approves Genentech’s Ocrevus (ocrelizumab) shorter 2-hour infusion for relapsing and primary progressive multiple sclerosis. News release. Genentech. December 14, 2020. Accessed April 24, 2023. https://www.businesswire.com/news/home/20201214005766/en/FDA-Approves-Genentech%E2%80%99s-Ocrevus-ocrelizumab-Shorter-2-Hour-Infusion-for-Relapsing-and-Primary-Progressive-Multiple-Sclerosis
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