DX45
Brain MRI Activity and Atrophy in Ocrelizumab-Treated Relapsing Multiple Sclerosis Patients in the Open-Label Extension of the Pooled Opera Trials

Thursday, May 31, 2018
Exhibit Hall A (Nashville Music City Center)
Anthony Traboulsee, MD , The University of British Columbia, Vancouver, BC, Canada
Douglas L Arnold, MD , NeuroRx Research, Montreal, QC, Canada
Ludwig Kappos, MD , University Hospital Basel, University of Basel, Basel, Switzerland
Stephen L Hauser, MD , University of California, San Francisco, CA
Xavier Montalban, MD, PhD , Vall díHebron University Hospital, Barcelona, Spain
Jerry S Wolinsky, MD , McGovern Medical School, UTHealth, Houston, TX
Victoria Levesque, PhD , Genentech, Inc., South San Francisco, CA
Pablo Villoslada, MD , Genentech, Inc., South San Francisco, CA
Shibeshih Belachew, MD, PhD , F. Hoffmann-La Roche Ltd, Basel, Switzerland
Fabian Model, PhD , F. Hoffmann-La Roche Ltd, Basel, Switzerland
Stanislas Hubeaux, MSc , F. Hoffmann-La Roche Ltd, Basel, Switzerland
Amit Bar-Or, MD , University of Pennsylvania, Philadelphia, PA
PDF


Background:

The efficacy and safety of ocrelizumab (OCR) in relapsing multiple sclerosis (RMS) were demonstrated in the 96-week double-blind control period of OPERA I and II (NCT01247324; NCT01412333). Upon completion of the controlled treatment period, all patients were eligible to enter an OCR open-label extension (OLE) phase.

Objectives:

To assess the efficacy of OCR therapy on MRI measures of disease activity and progression in the OLE period (2 years) of Phase III trials in RMS.

Methods:

During the double-blind controlled treatment period, patients received intravenous OCR 600 mg every 24 weeks or subcutaneous interferon beta-1a (IFN β-1a) 44 μg three times weekly for 96 weeks. At the start of the OLE period, patients continued (OCR-OCR) or were switched from IFN β-1a to OCR (IFN-OCR). MRI lesion activity (T1 gadolinium-enhancing [T1Gd+] lesions, new/enlarging T2 [N/ET2] lesions) and percentage change in whole brain volume (WBV), cortical grey matter volume (cGMV) and white matter volume (WMV) were analysed.

Results:

Among IFN-OCR patients, the adjusted number of T1Gd+ lesions was 0.48 lesions/scan at the time pre-switch, and decreased to 0.00 at Years 1 and 2 of OLE; similar reductions in adjusted number of N/ET2 lesions were seen from 2.16 lesions/scan in the year pre-switch to 0.33 and 0.08 at Years 1 and 2 of OLE. OCR-OCR continuers maintained low numbers of T1Gd+ and N/ET2 lesions through 2 years of OLE. OCR-OCR continuers versus IFN-OCR switchers had lower brain atrophy from core study baseline to the end of Years 1 and 2 of the OLE period measured by WBV change (–1.31%/–1.51% and –1.57%/–1.88%; p<0.01 for both); cGMV change (–1.47%/–1.56% and –1.72%/–1.91%; p=0.16 and p<0.01) and WMV change (–0.94%/–1.23% and –1.11%/–1.46%; p<0.01 for both).

Conclusions:

Switching from IFN β-1a to ocrelizumab at the start of the OLE period was associated with rapid and robust reductions in MRI disease activity. Patients initially randomized to ocrelizumab maintained lower whole brain, white matter and cortical grey matter tissue loss after 4 years of continuous treatment compared to those initiating ocrelizumab 2 years later.