Abstract
Importance
Preventing irreversible disability accumulation is a primary treatment goal in multiple sclerosis (MS).
Objective
To assess 10-year safety and efficacy of ocrelizumab (OCR) in patients with relapsing MS (RMS).
Design, Setting, and Participants
In 2 phase 3 multicenter randomized clinical trials (OPERA I and II), patients were randomized to OCR or interferon beta-1a (IFN) throughout a 2-year double-blind period (DBP) and entered an open-label extension (OLE) to receive OCR for up to an additional 8 years. Study periods were August 2011 to December 2022, with clinical cutoff on July 15, 2023. Data analyses were run between March 2023 and May 2026. Patients with RMS, aged 18 to 55 years, with an Expanded Disability Status Scale (EDSS) score of 0 to 5.5, and at least 1 relapse within the year before screening were eligible for inclusion.
Interventions
OCR (600 mg every 24 weeks) or IFN (44 µg 3 times weekly) in the DBP, then OCR during the OLE.
Main Outcomes and Measures
Outcomes included time to onset of 48-week confirmed disability progression (CDP) or progression independent of relapse activity (PIRA); time to reach EDSS score of 4.0 and 6.0; relapse rates; and incidence of adverse events (AEs) and serious AEs.
Results
A total of 1656 patients were randomized, and 1651 patients received either OCR (n = 825) or IFN (n = 826). A total of 1325 patients (80.0%) entered the OLE, of whom 853 (64.4%) completed the studies. A total of 1093 of 1656 patients (66.0%) were female; mean (SD) baseline age was 37.1 (9.2) years vs 37.2 (9.2) years in the OCR vs IFN arms, respectively. Over 10 years, continuous OCR (OCR-OCR) significantly reduced the hazard of 48-week CDP by 24% compared with delayed initiation (IFN-OCR; hazard ratio, 0.76; 95% CI, 0.61-0.95;
P
= .02), with 680 patients (82.2%) receiving OCR-OCR remaining free of 48-week CDP and 712 (86.1%) free of PIRA. OCR-OCR treatment reduced the hazard of progressing to key disability milestones, including EDSS of 4.0 (34%; hazard ratio, 0.66; 95% CI, 0.43-1.03;
P
= .06) and 6.0 (43%; hazard ratio, 0.57; 95% CI, 0.40-0.82;
P
= .002), with 502 (93.3%) and 774 (94.2%) retaining scores less than 4.0 and 6.0, respectively. In patients receiving OCR-OCR, relapse rates decreased from 0.139 at year 1 to 0.016 at year 10. Rates of AEs and SAEs, including serious infections, did not increase over the 8-year OLE.
Conclusions and Relevance
In the OPERA I and II randomized clinical trials, continuous OCR treatment over 10 years provided greater benefit in preserving function than a 2-year delay in initiating OCR, reinforcing the importance of early high-efficacy treatment.
Trial Registrations
ClinicalTrials.gov Identifiers:
NCT01247324
and
NCT01412333