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Emerging treatmentsPhase 3 study in peopleStudy completed

OPERA I and II: what 10 years of ocrelizumab follow-up show

Published by MyelinWatch:

Study sponsor
F. Hoffmann-La Roche Ltd
Funder
F. Hoffmann-La Roche Ltd

OPERA I and II (ocrelizumab) · The OPERA I and II Phase 3 trials studied ocrelizumab, an antibody that depletes CD20-positive B cells, in adults with relapsing multiple sclerosis (MS). For the first two years, participants were randomized to ocrelizumab or interferon beta-1a. Those entering the open-label extension then received ocrelizumab for up to eight more years. The October 2026 paper analyzes this follow-up after the trials ended.

What is the approach?

Ocrelizumab is an antibody that binds CD20 on B cells and reduces that immune-cell population. OPERA I and II compared this approach with interferon beta-1a for relapsing MS during the randomized period, then followed participants receiving ocrelizumab in an open-label extension; the extension is not a continuing randomized comparison.

Approach source: JAMA Neurology — original OPERA follow-up article ↗

What is being studied

The OPERA I and II Phase 3 trials studied ocrelizumab, an antibody that depletes CD20-positive B cells, in adults with relapsing multiple sclerosis (MS). For the first two years, participants were randomized to ocrelizumab or interferon beta-1a. Those entering the open-label extension then received ocrelizumab for up to eight more years. The October 2026 paper analyzes this follow-up after the trials ended.

Research stage

Phase 3 study in people

NCT01247324 and NCT01412333 are completed; any broader current programme status is not established

What we know so far

Of 1,656 originally randomized participants, 853 completed the studies. Across ten years, the earlier-ocrelizumab group had a lower hazard of 48-week confirmed disability progression than the group that started on interferon and later switched (hazard ratio 0.76; 95% confidence interval 0.61–0.95). The difference arose largely in the initial randomized period; the extension-only comparison was not significant (hazard ratio 1.02; 95% confidence interval 0.81–1.28). The comparison for progression independent of relapse activity (PIRA) was also not significant. Serious infections and lower IgG levels occurred despite no rising overall observed adverse-event rates in the extension.

What this means for patients today

The findings inform long-term discussions about treatment timing in relapsing MS, but they do not show ten years of randomized treatment comparison, an individual treatment recommendation, myelin repair or benefit in primary progressive MS. Attrition, open-label follow-up and post hoc analysis limit interpretation. The paper itself does not establish access or reimbursement in Greece.

Treatment or approach
OPERA I and II: long-term ocrelizumab follow-up in relapsing MS
How it is intended to work
Anti-CD20 B-cell depletion by ocrelizumab
Where the study is running
Multicenter studies; this paper does not establish Greek availability or reimbursement
Source: JAMA Neurology — peer-reviewed paper ↗Source: ClinicalTrials.gov — OPERA I (NCT01247324), completed with posted results ↗ Source: ClinicalTrials.gov — OPERA II (NCT01412333), completed with posted results ↗
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Last substantive MyelinWatch update

Programme updates — newest research developments first

  1. Post hoc analysis of two completed Phase 3 trials in relapsing MSResearch event/source date:

    OPERA trials: post hoc look at disability worsening in Black and Hispanic or Latino participants

    Researchers led by the University of Southern California, with authors from Genentech, Roche and other US centres, re-analysed the OPERA I and II trials, which compared ocrelizumab with interferon beta-1a for two years in relapsing multiple sclerosis (MS). In the interferon group, non-Hispanic Black and Hispanic or Latino participants had a higher risk of disability worsening confirmed after 24 weeks, measured with a combined (composite) disability measure, than non-Hispanic White participants (hazard ratio 3.0 and 2.3). Non-Hispanic Black and Hispanic or Latino participants also had more CD19-positive B cells at the start. In 1,138 participants who consented to genetic analysis, higher African or Americas genetic ancestry was also linked to higher risk. Ocrelizumab lowered B cells in all groups. Compared with interferon, it lowered the risk of this composite disability worsening in Hispanic or Latino participants (hazard ratio 0.38; 95% confidence interval 0.20–0.72). In the 65 Black participants the estimate also pointed to lower risk (hazard ratio 0.41), but the 95% confidence interval of 0.13–1.29 includes no difference, so the result is not statistically significant.

    Source: Multiple Sclerosis Journal (SAGE) — peer-reviewed primary article ↗Source: Multiple Sclerosis Journal — DOI 10.1177/13524585261496124 ↗ Source: ClinicalTrials.gov — OPERA I (NCT01247324), completed with posted results ↗ Source: ClinicalTrials.gov — OPERA II (NCT01412333), completed with posted results ↗

  2. Post hoc 10-year follow-up analysis of two Phase 3 trials in relapsing MSResearch event/source date:

    Ocrelizumab: full 10-year OPERA I and II analysis published

    Published online on 5 October 2026, the full OPERA I and II follow-up analysis covers 1,656 people randomized with relapsing multiple sclerosis (MS). Ocrelizumab was compared with interferon beta-1a for two blinded years; participants entering the open-label extension then received ocrelizumab for up to eight more years. Across the full period, earlier ocrelizumab was associated with a lower hazard of disability progression confirmed for 48 weeks (hazard ratio 0.76; 95% confidence interval 0.61–0.95). The difference was largely established during the randomized period. After the switch, the extension-only comparison did not show a new difference (hazard ratio 1.02; 95% confidence interval 0.81–1.28).

    Source: JAMA Neurology — peer-reviewed paper ↗Source: ClinicalTrials.gov — OPERA I (NCT01247324), completed with posted results ↗ Source: ClinicalTrials.gov — OPERA II (NCT01412333), completed with posted results ↗