Low Disease Activity Over 4 Years of Ocrelizumab Therapy in Treatment-Naive Patients With Early-Stage Relapsing-Remitting Multiple Sclerosis; the Phase IIIb ENSEMBLE Study
Robert Bermel1, Hans-Peter Hartung2, Bruno Brochet3, Ralph Benedict4, Thomas Berger5, William Carroll6, Timothy Vollmer7, Trygve Holmoy8, Rana Karabudak9, Joep Killestein10, Carlos Nos11, Francesco Patti12, Amy Perrin Ross13, Ludo Vanopdenbosch14, Jens Wuerfel15, Thomas Kuenzel15, Karen Kadner15, Inessa Kulyk15, Mark Freedman16
1Mellen Center for MS, Cleveland Clinic, Cleveland, OH, USA, 2Deptartment of Neurology, Heinrich-Heine-University Düsseldorf, Germany, 3Université de Bordeaux, Neurocentre Magendie INSERM, Bordeaux, France, 4Jacobs School of Medicine and Biomedical Sciences, Department of Neurology, University of Buffalo, NY, USA, 5Dept. of Neurology, Medical University of Vienna, 6Department of Neurology, Sir Charles Gairdner Hospital, Perron Institute for Neurological and Translational Science, The University of Western Australia, Nedlands, Australia, 7Department of Neurology, University of Colorado School of Medicine, Aurora, CO, USA, 8Department of Neurology, Akershus University Hospital, Lørenskog, Norway, 9Department of Neurology, Hacettepe University Faculty of Medicine, Ankara, Turkey, 10Department of Neurology, VU University Medical Centre, Amsterdam, The Netherlands, 11Centre d'Esclerosi Múltiple de Catalunya (Cemcat), Vall d’Hebron Hospital Universitari, Barcelona, Spain, 12Department of Medical and Surgical Sciences and Advanced Technologies, GF Ingrassia, Neuroscience Section and Multiple Sclerosis Centre, University of Catania PO Policlinico G Rodolico, Catania, Italy, 13Loyola University Chicago, Chicago, IL, USA, 14Department of Neurology, AZ Sint-Jan Brugge-Oostende, Brugge, Belgium, 15F. Hoffmann-La Roche Ltd, Basel, Switzerland, 16University of Ottawa, Department of Medicine and the Ottawa Hospital Research Institute Ottawa, ON, Canada.
Objective:

To report 4-year efficacy and safety data from the ENSEMBLE trial (NCT03085810) of ocrelizumab (OCR) in patients with early-stage relapsing-remitting multiple sclerosis (RRMS).

Background:

Early and sustained treatment of MS with high-efficacy therapy reduces the risk of long-term disease progression. ENSEMBLE is a multicenter, open-label, single-arm Phase IIIb study, evaluating the efficacy and safety of OCR in patients with early-stage RRMS.

Design/Methods:

At the time of enrollment, eligible patients were treatment naive, aged 18–55 years, had an active early-stage RRMS with a disease duration ≤3 years, Expanded Disability Status Scale (EDSS) ≤3.5 and ≥1 clinically reported relapse(s) or ≥1 signs of magnetic resonance imaging (MRI) activity (T1-weighted contrast-enhancing lesions or new/enlarging T2-weighted lesions, with MRI measurements rebaselined at W8) in the prior 12 months. Patients received OCR 600 mg every 24 weeks for 192 weeks. Key endpoints were no evidence of disease activity (NEDA)-3 (defined as no relapses, no 24-week [W] confirmed disability progression [CDP] and no MRI activity), annualized relapse rate (ARR), mean change in EDSS score from baseline (BL) and safety.

Results:

BL characteristics (N=678) were consistent with early-stage RRMS (patients ≤40 years with a median age of 31.0 years; duration since MS symptom onset, 0.78 years; duration since RRMS diagnosis, 0.24 years; mean BL EDSS score [SD], 1.71 [0.95]). At W192, the majority of patients had NEDA (n=394/593, 66.4%), 85.0% had no MRI activity, 90.9% had no relapses and 81.8% had no 24W-CDP. Adjusted ARR at W192 was low, 0.020 (95% CI, 0.015–0.027). No new or unexpected safety signals were observed.

Conclusions:

Disease activity based on clinical and MRI measures was minimal in most patients treated with ocrelizumab over 4 years in the ENSEMBLE study. Safety was consistent with the known profile of ocrelizumab, with no new signals.

10.1212/WNL.0000000000202202