2024 American Academy of Neurology Abstract Website

Stephen Hauser¹, Ludwig Kappos², Massimo Filippi³, Jerry Wolinsky⁴, Martin Weber⁵, Jacqueline Nicholas⁶, Cathy Chognot⁷, Hans-Martin Schneble⁷, Qing Wang⁷, Gavin Giovannoni⁸, Xavier Montalban⁹
¹UCSF Weill Institute for Neurosciences, ²University Hospital Basel, University of Basel, Research Center for Clinical Neuroimmunology and Neuroscience, ³Ospedale San Raffaele, Neuroimaging Research Unit, ⁴McGovern Medical School, UTHealth, ⁵Institute of Neuropathology and Department of Neurology, ⁶OhioHealth Riverside Methodist Hospital, ⁷F. Hoffmann-La Roche Ltd., ⁸Queen Mary University, ⁹Vall d’Hebron University Hospital

Objective:

To assess the long-term efficacy and safety of ocrelizumab (OCR) in patients with relapsing and primary progressive multiple sclerosis (pwRMS/pwPPMS).

Background:

OCR is a highly effective therapy approved for treatment of RMS and PPMS. Understanding the long-term efficacy and safety of OCR is critical considering the longer treatment durations associated with MS.

Design/Methods:

Patients randomized to receive OCR or comparator (interferon [IFN] β-1a in OPERA I/II [NCT01247324/NCT01412333]; placebo [PBO] in ORATORIO [NCT01194570]) either continued OCR (OCR-OCR) or switched from comparator to OCR (IFN-OCR; PBO-OCR) on entering the open-label extension studies. Disability accumulation (time to 48-week confirmed disability progression [48W-CDP] on Expanded Disability Status Scale [EDSS] and composite CDP [cCDP; 48W-CDP-EDSS, or ≥20% increases in Timed 25-Foot Walk or Nine-Hole Peg Test]) was analyzed up to Week 528. Safety outcomes were reported as rates per 100 patient years.

Results:

After 10 years, over three-quarters (76.6%) of pwRMS on OCR-OCR were free from 48W-CDP-EDSS events and 91.9% did not need a walking aid; risk of reaching either was significantly lower in pwRMS initiating OCR earlier versus delayed treatment (HR, CI: 0.77, 0.61–0.96; p=0.0183; 0.58, 0.41–0.84; p=0.003). In pwPPMS on OCR-OCR, after 10 years, 36.4% and 18.6% were free from 48W-CDP-EDSS and 48W-cCDP events, respectively, while most (80.4%) did not need a wheelchair; risk of reaching each was lower in pwPPMS initiating OCR earlier versus delayed treatment (HR, CI: 0.74, 0.61–0.91; p=0.0041; 0.78, 0.65–0.93; p=0.0064; 0.70, 0.48–1.03; p=0.0708). Over 10 years, (serious) adverse event rates were consistent with the controlled treatment period, treatment withdrawal was infrequent and malignancy rates remained within epidemiologic background. Serious infection rates were low and stable in both pwRMS and pwPPMS, irrespective of immunoglobulin G levels.

Conclusions:

Earlier treatment with ocrelizumab resulted in greater reductions in disability progression, with a favorable long-term safety profile in pwRMS and pwPPMS.