OPERA 9-Year
(2025)Objective
Ocrelizumab - To assess long-term efficacy and safety of ocrelizumab versus initial interferon β-1a in treatment-naive relapsing multiple sclerosis patients over 9 years.
Study Summary
• Early initiation led to better disability and brain volume outcomes compared with delayed switch from interferon
• Long-term safety profile remained stable with no new concerns
Intervention
Post hoc subgroup of OPERA I/II randomized controlled trials; patients received OCR or IFNβ-1a for 96 weeks, then OCR for 7-year open-label extension.
Inclusion Criteria
Treatment-naive patients with early relapsing MS, diagnosis within ≤2 years, mean baseline EDSS ~2.4.
Study Design
Arms: OCR–OCR (continuous ocrelizumab) vs IFN–OCR (interferon β-1a then switch to ocrelizumab)
Patients per Arm: OCR–OCR: 375; IFN–OCR: 382; Total: 757 (67% completed 9 years)
Outcome
• NEDA-3 at 9 years: 48.2% OCR–OCR vs 25.7% IFN–OCR
• Brain atrophy progression lower with OCR–OCR
• Safety stable: serious infections 1.3/100 PY, malignancy within expected rates
Bottom Line
Early and continuous treatment with ocrelizumab in treatment-naive patients with early RMS provides long-term benefits in controlling disease activity and preventing disability progression over 9 years. The benefits achieved by starting on ocrelizumab early were maintained long-term, and the disability and brain volume loss accrued by patients starting on interferon were not recovered after switching to ocrelizumab.
Major Points
- This is a post hoc exploratory analysis of a subgroup of 757 treatment-naive patients with early-stage RMS from the OPERA I/II trials and their open-label extension (OLE).
- Patients were initially randomized to ocrelizumab (OCR-OCR group) or interferon β-1a (IFN-OCR group) for a 96-week double-blind period (DBP), after which all patients received ocrelizumab in the OLE for a total follow-up of 9 years.
- The higher rate of achieving No Evidence of Disease Activity (NEDA-3) status with ocrelizumab during the DBP (72.5% vs 43.8% with interferon) was maintained throughout the 7-year OLE (48.2% vs 25.7%).
- Over 9 years, 78.7% of patients who started on and continued ocrelizumab remained free of 24-week confirmed disability progression (CDP).
- Brain volume loss that occurred during the initial 2 years of interferon treatment was not recovered after switching to ocrelizumab, although the rate of loss became similar between groups after the switch.
- No new safety signals were observed during the OLE, and the rate of infections remained low and stable over the >9 years of continuous ocrelizumab treatment.
Study Design
- Study Type
- Post hoc exploratory analysis of a subgroup from randomized controlled trials with a subsequent open-label extension.
- Randomization
- Yes
- Blinding
- The initial 96-week period was double-blind and double-dummy. The subsequent extension was open-label.
- Sample Size
- 757
- Follow-up
- 9 years
Primary Outcome
Definition: This analysis focused on long-term efficacy, primarily No Evidence of Disease Activity (NEDA-3) and 24-week Confirmed Disability Progression (CDP).
| Control | Intervention | HR/OR | P-value |
|---|---|---|---|
| - |
Limitations & Criticisms
- This was a post hoc exploratory analysis of a specific subgroup, not a prospectively defined primary analysis.
- Assessment bias could have been introduced due to the open-label nature of the extension period.
- Although the 9-year completion rate was high (67%), attrition bias remains a potential limitation.
Citation
Neurology 2025;104:e210142