Starting ocrelizumab two years later still showed as more disability at ten years

Design

Two phase 3 randomised trials with open-label extension to 10 years

Population

1,656 adults aged 18 to 55 with relapsing MS

Primary outcome

Time to 48-week confirmed disability progression

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 1,656 adults with relapsing MS to ocrelizumab or interferon beta-1a for two years. After that, almost everyone could take ocrelizumab in an open-label extension for up to eight more years. This report covers the full decade.

Patients on ocrelizumab from the start had a lower hazard of 48-week confirmed disability progression than those who switched after two years of interferon (HR 0.76, 95% CI 0.61 to 0.95). The hazard of reaching EDSS 6.0, needing a walking aid, was lower too (HR 0.57, 0.40 to 0.82); for EDSS 4.0 the estimate leaned the same way but was not significant. Among continuous ocrelizumab patients, 82.2% were free of confirmed progression at ten years, and the relapse rate fell from 0.139 in year one to 0.016 in year ten. Serious adverse events and infections did not rise over the extension.

The key point is that two years on a less effective drug left a gap that later treatment did not close. That supports offering high-efficacy therapy early to suitable patients rather than escalating after failure.

The extension was open-label and about a third did not complete it, which can bias long-term estimates. Cost and access to anti-CD20 drugs remain real barriers in India, where rituximab is sometimes used off-label instead.

• Consider high-efficacy therapy at diagnosis in suitable patients with relapsing MS rather than escalating later
• Explain to patients that lost ground from delayed treatment may not be recovered
• Monitor immunoglobulins and infection risk during long-term anti-CD20 therapy
• Check hepatitis B status before starting any anti-CD20 drug

Why it matters

It challenges the escalation approach of starting with a moderate drug and waiting for failure.

Don't overread it

The extension was open-label with about a third not completing, so long-term estimates may be biased.

The statistics, in plain English

An HR of 0.76 means about a quarter lower hazard of confirmed progression. Because the comparison was randomised for only the first two years, the ten-year difference reflects that early gap carried forward, with open-label follow-up and dropouts adding some uncertainty.

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