Long-Term Treatment With First-Line Ocrelizumab in Patients With Early RMS: 9-Year OPERA Subgroup Analysis
Joao Cerqueira1, Achim Berthele2, Bruce Cree3, Massimo Filippi4, Gabriel Pardo5, Owen Pearson6, Anthony Traboulsee7, Tjalf Ziemssen8, Timothy Vollmer9, Corrado Bernasconi10, Corey Mandel11, Inessa Kulyk10, Cathy Chognot10, Hans-Martin Schneble10, Kalpesh Prajapati12, Eva Havrdova13
12CA-Clinical Academic Centre Braga, Portugal Life and Health Sciences Research Institute, School of Medicine, University of Minho, Braga, Portugal, 2Department of Neurology, School of Medicine, Technical University of Munich, Munich, Germany, 3Department of Neurology, UCSF Weill Institute for Neurosciences, University of California San Francisco, San Francisco, CA, USA, 4Neurology Unit, Neurophysiology Service, Neurorehabilitation Unit, Neuroimaging Research Unit, Division of Neuroscience, IRCCS San Raffaele Scientific Institute, Milan, Italy, 5Multiple Sclerosis Center of Excellence, Oklahoma Medical Research Foundation, Oklahoma City, OK, USA, 6Department of Neurology, Morriston Hospital, Swansea, UK, 7Department of Neurology, University of British Columbia, Vancouver, BC, Canada, 8Center of Clinical Neuroscience, Department of Neurology, University Clinic Carl Gustav Carus, Dresden University of Technology, Dresden, Germany, 9Department of Neurology, Rocky Mountain Multiple Sclerosis Center at Anschutz Medical Campus, University of Colorado Denver, Denver, CO, USA, 10F. Hoffmann-La Roche Ltd, Basel, Switzerland, 11Genentech, Inc., San Francisco, CA, USA, 12IQVIA Solutions, Inc., Amsterdam, The Netherlands, 13Department of Neurology and Center of Clinical Neuroscience, General University Hospital and Charles University, Prague, Czech Republic

To assess the efficacy and safety of first-line ocrelizumab (OCR) in a subgroup of treatment-naive patients (N=757) with early relapsing multiple sclerosis (RMS) (diagnosis ≤2 years) from the OPERA I/II trials (NCT01247324/NCT01412333) over 9 years of follow-up.


The benefits and risks of highly effective therapy as first-line treatment early in RMS should inform evidence-based decisions, to improve patient outcomes compared with escalating from low efficacy treatments.


Patients were randomized to OCR or interferon (IFN)-β-1a during the 96-week, double-blind period (DBP). In the open-label extension (OLE), patients continued with OCR (OCR–OCR) or switched to OCR (IFN–OCR). Efficacy endpoints included no evidence of disease activity (NEDA) with MRI rebaselining at Week 24 (defined as absence of: Protocol-defined relapses, 24-week confirmed disability progression [24W-CDP], contrast-enhancing T1-weighted and new/enlarging T2-weighted lesions) and annualized relapse rate. Safety measures included incidence/nature of adverse events (AEs) and the association between immunoglobulin (Ig)G below the lower limit of normal (LLN) and serious infections (SIs).


Of 757 analyzed patients (OCR, 375; IFN, 382), 67% remained on treatment for over 9 years (OCR, 69%; IFN, 65%). During DBP, a higher proportion of OCR-treated patients, compared with IFN, had NEDA (72% vs 44%; p<0.001) and no 24W-CDP (92% vs 88%; p=0.062). In DBP+OLE, OCR–OCR patients had higher rates of NEDA compared with IFN–OCR (48% vs 26%; p<0.001) and no 24W-CDP (79% vs 75%; p=0.2) or relapses (0.05 vs 0.09; p=0.004). Rates of AEs, serious AEs, SIs and malignancies remained low over 9 years of OCR treatment. In DBP+OLE, 1.8% (12/668) of patients reported SIs during periods of IgG <LLN, with comparable types, characteristics and treatment outcomes to the overall SI profile over 9 years.


In this treatment-naive, early RMS OPERA subgroup, long-term safety and efficacy data over 9 years support the use of ocrelizumab as first-line therapy.