Early Ocrelizumab Shows Sustained Long-Term Benefit in Relapsing MS
Key Clinical Summary:
- In the OPERA I and II trials, continuous ocrelizumab treatment for up to 10 years was associated with greater disability and relapse control than initiating ocrelizumab after 2 years of interferon beta-1a treatment in patients with relapsing multiple sclerosis (RMS).
- Continuous ocrelizumab reduced the hazard of 48-week confirmed disability progression (CDP) by 24%, with 82.2% of patients remaining free of 48-week CDP and 86.1% remaining free of progression independent of relapse activity (PIRA).
- Relapse rates among patients receiving continuous ocrelizumab declined from 0.139 at year 1 to 0.016 at year 10, while rates of adverse events and serious adverse events did not increase during the 8-year open-label extension (OLE).
Treatment with ocrelizumab for up to 10 years was associated with sustained relapse control and minimal disability accrual in patients with RMS, according to results from the phase 3 OPERA I and II trials. Published in JAMA Neurology, the findings also suggest that earlier treatment initiation was associated with more favorable long-term disability outcomes.
Study Findings
OPERA I and II enrolled patients aged 18 to 55 years with RMS, an Expanded Disability Status Scale (EDSS) score of 0 to 5.5, and at least 1 relapse within the year before screening.
Patients were randomized to receive either 600 mg of intravenous ocrelizumab every 24 weeks or 44 µg of subcutaneous interferon beta-1a 3 times weekly. Those who completed the initial double-blind controlled treatment period were then eligible to enter an 8-year OLE phase. During the extension, all patients received ocrelizumab regardless of their original assignment.
A total of 1651 patients received either ocrelizumab (n = 825) or interferon beta-1a (n = 826) in the double-blind period. Of these participants, 1325 entered the OLE and a subsequent 853 completed the studies.
Over 10 years, continuous ocrelizumab significantly reduced the hazard of 48-week CDP by 24% compared to initial treatment with interferon beta-1a (IFN-OCR; hazard ratio [HR], 0.76; 95% CI, 0.61-0.95; P = .02). In participants who received ocrelizumab throughout the entire 10-year period, 680 (82.2%) remained free of 48-week CDP and 712 (86.1%) remained free of PIRA.
Continuous ocrelizumab was also associated with a 34% lower hazard of reaching an EDSS score of 4.0 (HR, 0.66; 95% CI, 0.43-1.03; P = .06) and a 43% lower hazard of reaching an EDSS score of 6.0 (HR, 0.57; 95% CI, 0.40-0.82; P = .002). In this group, 502 patients (93.3%) and 774 patients (94.2%) retained EDSS scores below 4.0 and 6.0, respectively.
Those continuously treated with ocrelizumab additionally saw a decrease in relapse rate from 0.139 at year 1 to 0.016 at year 10. Rates of adverse events and serious adverse events, including serious infections, did not increase during the 8-year OLE.
Clinical Implications
A key challenge in multiple sclerosis management is preventing the accumulation of disability as the disease progresses, particularly as relapse and PIRA may contribute to worse functional outcomes. The results of OPERA I and II suggest that long-term treatment with ocrelizumab may be a safe and effective option for RMS.
The findings also underscore the importance of early initiation, as those who experienced a 2-year delay in receiving ocrelizumab saw less favorable long-term disability outcomes compared to those treated consistently over the 10-year study period.
Expert Commentary
“This 10-year analysis of the OPERA I and II randomized clinical trials confirms the significant and durable impact of ocrelizumab on the long-term course of RMS,” wrote Stephen L. Hauser, MD, Weill Institute for Neurosciences, University of California, San Francisco, and study coauthors.
The researchers concluded that the lack of new or cumulative safety signals throughout the study confirmed “a favorable long-term benefit-risk profile with ocrelizumab in the management of patients with RMS.”
