2023 American Academy of Neurology Abstract Website

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

Objective:

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.

Background:

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.

Design/Methods:

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).

Results:

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.

Conclusions:

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.