Ocrevus (ocrelizumab) demonstrates superior long-term outcomes in delaying disease progression when used as a first-line treatment for early-stage relapsing forms of multiple sclerosis (MS), according to nine-year data from the OPERA I and OPERA II Phase 3 trials. The findings, published in Neurology, support the early use of high-efficacy therapy to improve clinical outcomes in patients diagnosed with early-stage relapsing MS.
The OPERA I (NCT01247324) and OPERA II (NCT01412333) trials initially assigned participants to either Ocrevus or Rebif (interferon beta-1a) for two years, followed by an open-label extension where all participants received Ocrevus. The analysis focused on treatment-naive patients diagnosed with relapsing MS within two years prior to enrollment.
Sustained NEDA-3 Achievement
After nine years, 48.2% of patients who started on Ocrevus achieved no evidence of disease activity (NEDA-3), defined as the absence of relapses, MRI activity, and confirmed disability worsening. This was nearly twice the rate (25.7%) observed in patients who initially started on Rebif and later switched to Ocrevus. The study included 757 patients across both trials, with 382 initially assigned to Ocrevus and 375 to Rebif.
Impact on Disability Progression and Relapse Rates
While disability progression rates became similar between the two groups after Rebif patients switched to Ocrevus, the initial benefits observed in the Ocrevus group during the first two years were sustained. This resulted in the Rebif group having greater disability levels after nine years due to faster disease progression during the initial Rebif treatment period.
Relapse rates were also significantly lower among Ocrevus patients over the nine-year period (0.05 vs. 0.09), reflecting the higher relapse rates experienced by the Rebif group during the main trials. Similar benefits were observed regarding brain volume loss, a key indicator of neurodegeneration.
ENSEMBLE Study Reinforces Findings
These findings are further supported by the ENSEMBLE study, a prospective, 4-year, international, multicenter, single-arm, open-label, phase IIIb study. The study evaluated the effectiveness and safety of ocrelizumab as a first-line therapy in treatment-naive patients with recently diagnosed relapsing-remitting MS (RRMS). At week 192, most of the patients had NEDA-3 (66.4%), 85.0% had no MRI activity, 90.9% had no relapses, and 81.8% had no 24-week CDP over the study duration. Adjusted ARR at week 192 was low (0.020, 95% CI 0.015-0.027).
Safety Profile
The overall safety profile of Ocrevus remained consistent throughout the study, with no new safety signals observed during the open-label extension phase. The most commonly reported side effects were infections, but their rates remained low and stable over nine years of continuous Ocrevus treatment.
Clinical Implications
The results underscore the importance of initiating high-efficacy therapy, such as Ocrevus, early in the disease course of relapsing MS. The data suggest that this approach can provide beneficial short-term and long-term effects on disease progression compared with an escalation approach. "It is important to note that the higher disability accrual and average brain volume loss observed during the [two] years on [Rebif] treatment were not recovered, even after switching to [Ocrevus], indicating that initiating treatment with [Ocrevus] earlier in the disease course is beneficial to patients," the researchers wrote.
