Earlier Start, Less MS Disability at 10 Years

Ten-year data confirmed the durable clinical benefit of the anti-CD20 monoclonal antibody ocrelizumab and reinforced the importance of early initiation in patients with relapsing multiple sclerosis (MS).Long-term follow-up data from the OPERA I and OPERA II trials showed that patients initially assigned to ocrelizumab retained an advantage over those who received interferon beta-1a for 2 years before switching.Earlier treatment was associated with a 24% lower hazard of disability progression confirmed for 48 weeks and a 43% lower hazard of needing a walking aid.Relapse activity remained low with continued treatment, and no new or cumulative safety signals emerged, reported investigators led by Stephen L. Hauser, MD, of the UCSF Weill Institute for Neurosciences at the University of California, San Francisco.The findings were published online on October 5 in JAMA Neurology.Lasting BenefitDuring the double-blind phase of the OPERA I and II trials, 1656 adults with relapsing MS were randomly assigned in a 1:1 ratio to intravenous ocrelizumab (600 mg every 24 weeks) or subcutaneous interferon beta-1a (44 µg 3 times per week) for 2 years. A total of 1325 patients entered the extension phase, and all received ocrelizumab for up to 8 more years.Among patients assigned to ocrelizumab from the outset, 82.2% remained free of disability progression confirmed for 48 weeks over the 10-year follow-up. The hazard was lower than among those who switched after 2 years of interferon treatment (hazard ratio [HR], 0.76; P = .02).Early continuous ocrelizumab treatment reduced the hazard of reaching key disability milestones, including an Expanded Disability Status Scale (EDSS) score of 4.0 (34%; HR, 0.66; P = .06) and 6.0 (43%; HR, 0.57; P = .002), with 93.3% and 94.2% remaining below those thresholds, respectively.Over 10 years, 73.0% of patients receiving continuous ocrelizumab remained free from relapse, compared with 63.2% of those who initially received interferon beta-1a, corresponding to a 38% reduction in relapse risk (P < .001).“The number of relapses decreased consistently over time, and in year 10, only approximately 1 out of 100 patients experienced a relapse,” the investigators reported. MRI activity was also rapidly suppressed and remained near-completely suppressed during follow-up. In addition, 58.6% of patients treated continuously with ocrelizumab had no evidence of disease activity over 10 years, compared with 38.0% of patients who initially received interferon (P < .001).No New Long-Term Safety SignalsAmong 1448 patients exposed to ocrelizumab, which represents more than 10,800 patient-years of exposure, rates of adverse events and serious adverse events did not increase over time. Serious infections occurred at a rate of 1.8 per 100 patient-years and remained generally stable. Mean immunoglobulin G (IgG) levels declined but remained within the normal range overall, with 84.5% of patients maintaining levels above the lower limit of normal. Prolonged exposure was not associated with an increasing risk for serious infection, regardless of IgG status. Malignancy rates also remained stable and were similar to rates in the general population and in external MS cohorts.The investigators cautioned that the open-label extension lacked a contemporaneous control group and that the analysis was post hoc. Attrition was another limitation, with slightly more than half of patients initially randomly assigned completing the full 10-year follow-up.Despite these limitations, the authors said the data support a favorable long-term benefit-risk profile for ocrelizumab and reinforce the importance of early initiation.This research was funded by F. Hoffmann-La Roche. Several authors reported relationships with Roche and other pharmaceutical companies.