2026 American Academy of Neurology Abstract Website

Gavin Giovannoni¹, Laura Airas², Riley Bove³, Gary Cutter⁴, Jeremy Hobart⁵, Jens Kuhle⁶, Xavier Montalban⁷, Carmen Tur⁸, Jerry Wolinsky⁹, Hans-Martin Schneble¹⁰, Anna Baldinotti¹⁰, Ulrike Bonati¹⁰, Caroline Giacobino¹⁰, Qing Wang¹⁰, Ke Yang¹⁰, Jiwon Oh¹¹
¹Department of Neurology, Royal London Hospital, Barts Health NHS Trust, London, UK and Blizard Institute, Queen Mary University, London, UK, ²University of Turku, Turku, Finland, ³UCSF Weill Institute for Neuroscience, Department of Neurology, University of California San Francisco, San Francisco, CA, USA, ⁴The University of Alabama at Birmingham, School of Public Health, Birmingham, AL, USA, ⁵Peninsula Medical School, Plymouth University, UK, ⁶MS Center and Research Center for Clinical Neuroimmunology and Neuroscience Basel (RC2NB), University Hospital Basel, University of Basel, Basel, Switzerland, ⁷Centre d'Esclerosi Múltiple de Catalunya, Vall d'Hebron University Hospital, Barcelona, Spain, ⁸Queen Square MS Centre, Department of Neuroinflammation, Institute of Neurology, Faculty of Brain Sciences, University College London (UCL), London, UK/Neurology-Neuroimmunology Department, Multiple Sclerosis Centre of Catalonia (CEMCAT), Vall d'Hebron Barcelona Hospital Campus, Barcelona, Spain, ⁹Department of Neurology, University of Texas Health Science Center, Houston, TX, USA, ¹⁰F. Hoffmann-La Roche Ltd, Basel, Switzerland, ¹¹Division of Neurology, Department of Medicine, St. Michael's Hospital, University of Toronto, Toronto, Ontario, Canada

Objective:

ORATORIO-HAND (NCT04035005) evaluated the efficacy and safety of ocrelizumab in patients with primary progressive multiple sclerosis (pwPPMS), including older pwPPMS and those with more-advanced disease.

Background:

ORATORIO (NCT01194570) showed superiority of ocrelizumab vs placebo in delaying disability progression in pwPPMS. The impact of ocrelizumab in older and more-advanced pwPPMS is not fully understood, particularly in preventing hand-function worsening.

Design/Methods:

Adult pwPPMS (≤65 years, Expanded Disability Status Scale [EDSS] score: 3.0-8.0) were randomized 1:1 to ocrelizumab 600 mg or placebo every 6 months for 144 weeks or until ≥340 progression events, whichever occurred earlier. The primary endpoint was a composite of time to onset of 12-week confirmed disability progression (12W-cCDP) in 9-Hole Peg Test (CDP-9HPT ≥20% worsening from baseline) or EDSS (CDP-EDSS) in all randomized and a subset of MRI-active patients.

Results:

In ocrelizumab (n=505) and placebo (n=508) patients, baseline median (range) age was 48 (18-66) vs 47 (22-66) years and EDSS was 6.0 (3.0-8.0) vs 6.0 (2.5-8.0); median treatment duration was 144.0 and 143.7 weeks. The percentage of ocrelizumab and placebo patients with 12W-cCDP was 32.7% vs 40.4% (hazard ratio [HR] [95% CI]: 0.70 [0.57-0.86]; risk reduction [RR], 30%; P=0.0007); 16.7% vs 24.9% on 9HPT (RR, 41%; P=0.0002) and 23.0% vs 30.8% on EDSS (RR, 33%; P=0.0013). In the MRI-active subset, the percentage of patients with 12W-cCDP was 26.8% vs 45.9% (HR [95% CI]: 0.45 [0.31-0.64], RR, 55%; P<0.0001), with significant RRs observed in CDP-9HPT (62%) and CDP-EDSS (59%). The safety profile was similar between both arms, apart from infusion-related reactions (20.8% ocrelizumab vs 4.3% placebo) and infections (48.4% vs 44.7%). Additional results will be presented.

Conclusions:

In pwPPMS including those with more-advanced disease, ocrelizumab was superior to placebo in delaying overall disability progression and upper-limb–function worsening. Adverse events reported were consistent with the known ocrelizumab safety profile.