Design: Two phase 3 randomised trials with 8-year open-label extension (OPERA I and II)
Population: 1656 adults aged 18 to 55 with relapsing multiple sclerosis
Primary outcome: 48-week confirmed disability progression over 10 years
Effect: Early vs delayed ocrelizumab HR 0.76 (95% CI 0.61 to 0.95); EDSS 6.0 HR 0.57 (0.40 to 0.82)

OPERA I and II randomised 1656 adults with relapsing multiple sclerosis to ocrelizumab or interferon beta-1a for two years, after which all could take ocrelizumab in an open-label extension for up to eight more years. 80% entered the extension and 64% of those completed it.

Over ten years, starting ocrelizumab immediately rather than two years later reduced 48-week confirmed disability progression by 24% (hazard ratio 0.76, 95% CI 0.61 to 0.95). The hazard of reaching EDSS 6.0, needing a walking aid, was 43% lower (0.57, 0.40 to 0.82); for EDSS 4.0 the reduction did not reach significance (0.66, 0.43 to 1.03). 82% of the early group remained free of confirmed progression. Relapse rates fell to 0.016 a year by year ten, and serious adverse events, including serious infections, did not rise over time.

The finding supports starting high-efficacy therapy early rather than escalating after failure. In India, cost and access shape the choice, and biosimilar or off-label anti-CD20 options such as rituximab are widely used; this trial did not test them. The comparison after year two is between two groups who were both on ocrelizumab, and dropout over ten years limits certainty.

Discuss high-efficacy therapy at diagnosis of active relapsing MS rather than after a first-line failure.
Explain that a two-year delay in effective treatment was not made up over ten years.
Monitor immunoglobulins and infection risk on long-term anti-CD20 therapy.
Weigh cost and access openly; anti-CD20 alternatives are often used in India.

Why it matters

Early disability in MS appears to be permanent, so the first treatment choice carries forward.

The statistics, in plain English

A hazard ratio of 0.76 means a 24% lower rate of confirmed worsening at any point. The EDSS 4.0 result's interval crosses 1, so that milestone could not be confirmed. After two years the trial was open-label and a third of patients did not complete, which can bias long-term comparisons.