OPERA I & II
Ocrelizumab
The identically designed OPERA I and II trials showed that ocrelizumab outperformed high-dose subcutaneous interferon beta-1a across relapse, disability, and MRI outcomes.
- Phase
- Phase III × 2
- Population
- Relapsing multiple sclerosis (RMS)
- Controlled period
- Aug 31, 2011 — May 12, 2015
What was compared
Ocrelizumab
600 mg intravenously every 24 weeks
Interferon beta-1a
44 μg subcutaneously three times weekly
Primary endpoint
Annualized relapse rate
96 weeks
Primary endpoint results
Annualized relapse rate in each OPERA trial
Relapses per participant-year
46% lower in OPERA I and 47% lower in OPERA II (P<0.001 for both).
Selected secondary outcomes
9.1% versus 13.6% in pooled analysis; HR 0.60 (P<0.001).
94% and 95% lower with ocrelizumab in OPERA I and II.
Study population
- Randomized
- 1,656 randomized across both trials
- Age
- Mean about 37 years; eligible 18–55
- Sex
- 1,093 women (66%)
- Disability
- EDSS 0–5.5
- Disease definition
- Relapsing multiple sclerosis with recent clinical activity
Who entered the trial
Key inclusion criteria
- Defined based on McDonald criteria 2010
- At least two attacks in 2 years or one attack in the prior year
- Neurologic stability before baseline and EDSS 0–5.5
Key exclusion criteria
- Primary progressive MS
- Chronic immunosuppression, immunodeficiency, or active/recurrent infection
- Prior severe reaction to monoclonal antibodies or major MRI contraindication
Safety signal
- Infusion-related reactions occurred in 34.3% with ocrelizumab.
- Serious infection occurred in 1.3% with ocrelizumab and 2.9% with interferon.
- Neoplasms occurred in 0.5% and 0.2%, respectively; longer observation was required.
Why it mattered
Replicated superiority in two large trials established CD20-positive B-cell depletion as a major therapeutic strategy in relapsing MS.
Important limitation
The 96-week trials could not define long-term immune, infection, or malignancy risk, and some secondary outcomes rely on prespecified pooled analysis.