ORATORIO

Ocrelizumab

ORATORIO showed that ocrelizumab delayed disability progression in primary progressive multiple sclerosis.

Phase
Phase III
Population
Primary progressive multiple sclerosis (PPMS)
Controlled period
Mar 2, 2011 — Jul 23, 2015

What was compared

Randomized 2:1Double-blindPlacebo-controlledEvent-driven
Intervention

Ocrelizumab

600 mg intravenously every 24 weeks

n=488
Comparator

Placebo

Matching intravenous infusions every 24 weeks

n=244
732 randomizedAt least 120 weeks controlled phase

Primary endpoint

Prespecified outcome

12-week confirmed disability progression

Event-driven follow-up

Outcome figure

Primary endpoint results

Intervention Comparator or reference

12-week confirmed disability progression

Participants with progression (%)

Event-driven follow-up
Ocrelizumab
32.9%
Placebo
39.3%

HR 0.76 (95% CI 0.59–0.98; P=0.03).

Selected secondary outcomes

24-week confirmed disability progression

29.6% versus 35.7%; HR 0.75 (P=0.04).

Timed 25-foot walk and MRI

Walking deterioration and MRI lesion/brain-volume outcomes favored ocrelizumab.

Study population

Randomized
732 randomized
Age
Mean 44.6 years; eligible 18–55
Sex
361 women (49%)
Disability
EDSS 3.0–6.5
Disease definition
Primary progressive multiple sclerosis

Who entered the trial

Key inclusion criteria

  • Defined based on McDonald criteria 2005
  • Baseline EDSS 3.0–6.5
  • Restricted disease duration based on baseline disability

Key exclusion criteria

  • Relapsing-remitting, secondary progressive, or progressive-relapsing MS
  • Prior B-cell therapy or specified potent immunosuppressive treatment
  • Active or recurrent infection, malignancy, or inability to undergo MRI

Safety signal

  • Infusion reactions, upper-respiratory infections, and oral herpes were more frequent with ocrelizumab.
  • Neoplasms occurred in 2.3% with ocrelizumab and 0.8% with placebo.

Why it mattered

ORATORIO provided the first pivotal evidence supporting an approved disease-modifying therapy for primary progressive MS.

Important limitation

Age, disability, and disease-duration criteria selected a narrower and generally earlier PPMS population than many patients seen in practice.

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