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A Method of Trigonometric Modelling of Seasonal Variation Demonstrated with Multiple Sclerosis Relapse Data
Published on: December 9, 2015
Onset of clinical and MRI efficacy of ocrelizumab in relapsing multiple sclerosis
Frederik Barkhof1, Ludwig Kappos2, Jerry S Wolinsky2
1From the Department of Radiology and Nuclear Medicine (F.B.), VU University Medical Centre, Amsterdam, the Netherlands; UCL Institutes of Healthcare Engineering and Neurology (F.B.), London, UK; Neurologic Clinic and Policlinic, Departments of Medicine, Clinical Research, Biomedicine and Biomedical Engineering (L.K.), University Hospital Basel, University of Basel, Switzerland; Department of Neurology (J.S.W.), McGovern Medical School, UTHealth, Houston, TX; Department of Radiology (D.K.B.L.), University of British Columbia, Vancouver, Canada; Department of Neurology and Center for Neuroinflammation and Experimental Therapeutics (A.B.-O.), University of Pennsylvania, Philadelphia; Department of Neurology, Medical Faculty (H.-P.H.), Heinrich-Heine University Düsseldorf, Germany; F. Hoffmann-La Roche Ltd. (S.B., A.S., J.N., H.K.), Basel, Switzerland; Genentech, Inc. (J.H., L.J.), South San Francisco; and Department of Neurology (S.L.H.), University of California, San Francisco. During completion of the work related to this article, S. Belachew was an employee of F. Hoffmann-La Roche Ltd.; his current affiliation is Biogen, Cambridge, MA. f.barkhof@vumc.nl.
Objective:
To assess the onset of ocrelizumab efficacy on brain MRI measures of disease activity in the phase II study in relapsing-remitting multiple sclerosis (RRMS), and relapse rate in the pooled phase III studies in relapsing multiple sclerosis (RMS).
Methods:
Brain MRI activity was determined in the phase II trial at monthly intervals in patients with RRMS receiving placebo, ocrelizumab (600 mg), or intramuscular interferon (IFN) β-1a (30 μg). Annualized relapse rate (ARR; over various epochs) and time to first relapse were analyzed in the pooled population of the phase III OPERA (A Study of Ocrelizumab in Comparison With Interferon Beta-1a [Rebif] in Participants With Relapsing Multiple Sclerosis) I and OPERA II trials in patients with RMS receiving ocrelizumab (600 mg) or subcutaneous IFN-β-1a (44 μg).
Results:
In patients with RRMS, ocrelizumab reduced the number of new T1 gadolinium-enhancing lesions by week 4 vs placebo (p = 0.042) and by week 8 vs intramuscular IFN-β-1a (p < 0.001). Ocrelizumab also reduced the number of new or enlarging T2 lesions appearing between weeks 4 and 8 vs both placebo and IFN-β-1a (both p < 0.001). In patients with RMS, ocrelizumab significantly reduced ARR (p = 0.005) and the probability of time to first protocol-defined relapse (p = 0.014) vs subcutaneous IFN-β-1a within the first 8 weeks.
Conclusion:
Epoch analysis of MRI-measured lesion activity in the phase II study and relapse rate in the phase III studies consistently revealed a rapid suppression of acute MRI and clinical disease activity following treatment initiation with ocrelizumab in patients with RRMS and RMS, respectively.
Classification Of Evidence:
This study provides Class II evidence that for patients with RRMS and RMS, ocrelizumab suppressed MRI activity within 4 weeks and clinical disease activity within 8 weeks.
Insights
Ocrelizumab rapidly suppressed brain MRI lesions in relapsing-remitting multiple sclerosis (RRMS) within 4 weeks and reduced relapse rates in relapsing multiple sclerosis (RMS) within 8 weeks.
Area of Science:
- Neuroimmunology
- Clinical Neurology
- Pharmacology
Background:
- Multiple sclerosis (MS) is a chronic autoimmune disease affecting the central nervous system.
- Relapsing forms of MS (RMS) and relapsing-remitting MS (RRMS) are characterized by inflammatory lesions and clinical relapses.
- Ocrelizumab is a targeted B-cell depleting therapy investigated for MS treatment.
Purpose of the Study:
- To evaluate the early efficacy of ocrelizumab on MRI-assessed disease activity in RRMS.
- To determine the onset of ocrelizumab's effect on relapse rates in RMS.
Main Methods:
- Phase II trial: Monthly MRI assessment of T1 gadolinium-enhancing and T2 lesions in RRMS patients treated with ocrelizumab, placebo, or interferon-beta-1a.
- Phase III (OPERA I & II) trials: Analysis of annualized relapse rate (ARR) and time to first relapse in RMS patients receiving ocrelizumab or subcutaneous interferon-beta-1a.
Main Results:
- Ocrelizumab significantly reduced new T1 gadolinium-enhancing lesions by week 4 (vs placebo) and week 8 (vs interferon-beta-1a) in RRMS.
- Ocrelizumab decreased new or enlarging T2 lesions between weeks 4-8 in RRMS compared to placebo and interferon-beta-1a.
- In RMS, ocrelizumab significantly lowered ARR and time to first relapse within 8 weeks compared to subcutaneous interferon-beta-1a.
Conclusions:
- Ocrelizumab demonstrates rapid suppression of MRI-measured disease activity in RRMS.
- Early clinical efficacy, shown by reduced relapse rates, was observed in RMS patients treated with ocrelizumab.
- Class II evidence indicates ocrelizumab's prompt action on both MRI and clinical disease markers in MS.
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