2023 American Academy of Neurology Abstract Website

Martin Weber¹, Ludwig Kappos², Stephen Hauser³, Hans-Martin Schneble⁴, Qing Wang⁴, Gavin Giovannoni⁵
¹Institute of Neuropathology and Department of Neurology, University Medical Centre, Göttingen, Germany, and Fraunhofer-Institute for Translational Medicine and Pharmacology ITMP, Göttingen, Germany, ²Research Center for Clinical Neuroimmunology and Neuroscience, University Hospital Basel, University of Basel, Basel, Switzerland, ³UCSF Weill Institute for Neurosciences, University of California San Francisco, San Francisco, CA, USA, ⁴F. Hoffmann-La Roche Ltd, Basel, Switzerland, ⁵Queen Mary University of London, London, UK

Objective:

To assess the efficacy of earlier initiation of ocrelizumab on reaching key disability milestones, after 8.5 years of follow-up in the double-blind period (DBP) and open-label extension (OLE) of the pooled OPERA I/II (NCT01247324/NCT01412333) studies in patients with relapsing multiple sclerosis.

Background:

Early intervention using high-efficacy therapies to prevent disease progression is an increasingly adopted therapeutic strategy in multiple sclerosis, as reaching disability milestones is associated with increased patient and societal burden.

Design/Methods:

Patients completing the DBP either continued ocrelizumab (OCR-OCR) or switched from interferon β-1a to ocrelizumab (IFN-OCR) when entering the OLE period. Time-to-onset of 24-week confirmed disability progression to Expanded Disability Status Scale (EDSS) scores reflecting onset of impairment perceived by the patient (EDSS ≥2.0 from baseline EDSS ≤1.0), walking impairment (EDSS ≥4.0 from baseline EDSS ≤3.0) and requiring a walking aid (EDSS ≥6.0 from baseline EDSS ≤5.5) since DBP baseline were analyzed.

Results:

Over 8.5 years of the DBP and OLE, the risk of reaching key disability milestones was significantly lower in those who initiated ocrelizumab earlier (OCR-OCR) vs delayed treatment (IFN-OCR) (Hazard Ratio [95% confidence interval]): onset of disability (EDSS ≥2.0: n=9/61 vs n=20/82; 0.42 [0.19–0.94]; p=0.0303); walking impairment (EDSS ≥4.0: n=49/538 vs n=62/544; 0.69 [0.47–1.00]; p=0.0486); requiring a walking aid (EDSS ≥6.0: n=61/822 vs n=79/823; 0.67 [0.48–0.94]; p=0.0207). Over 8.5 years, 85.2%, 90.9% and 92.6% of OCR-OCR patients had not progressed to EDSS ≥2.0, EDSS ≥4.0 and EDSS ≥6.0 from the respective baseline.

Conclusions:

After 8.5 years of follow-up, earlier treatment with ocrelizumab was associated with reduced numbers of patients reaching early disability milestones. Early institution of high-efficacy therapy can preserve function that is not regained when the same treatment is initiated later.