Ocrelizumab Showed No Evidence of Disease Activity in Early-Remitting MS

Joao J. Cerqueira, MD, PhD

Recent data from a subgroup analysis of the OPERA I/II (NCT01247324/NCT01412333) trials with over 9 years of follow-up with ocrelizumab (Ocrevus; Genentech) showed no evidence of disease activity in a high portion of treatment-naive patients with early relapsing multiple sclerosis (RMS).

During the double-blinded period, no evidence of disease activity (72% vs 44%; P <.001) and no 24-week confirmed disability progression (92% vs 88%; P = .062) was observed in a higher proportion of ocrelizumab-treated patients compared with interferon-β-1a. In double blinded period and open label extension, patients that continued with ocrelizumab had higher rates of no evidence of disease activity(48% vs 26%; P <.001) and no 24-week confirmed disability progression (79% vs 75%; P = .2) or relapses (0.05 vs 0.09; P = .004) compared those who switched to ocrelizumab.

The findings were presented as an abstract at the 2023 American Academy of Neurology (AAN) Annual Meeting, April 22-27, in Boston, Massachusetts, by lead author Joao J. Cerqueira, MD, PhD, associate professor of neurology, School of Medicine, University of Minho, Braga, Portugal. Cerqueira and colleagues noted that the results support the use of treatment as first-line therapy for RMS.

Patients were randomized to ocrelizumab or interferon β-1a during the 96-week, double-blind period. In the open-label extension, patients continued with ocrelizumab or switched to ocrelizumab. The efficacy end points included no evidence of disease activity with MRI rebaselining at week 24, defined as absence of protocol-defined relapses, 24-week confirmed disability progression, contrast-enhancing T1-weighted and new/enlarging T2-weighted lesions; and annualized relapse rate. The safety measures were the incidence/nature of adverse events and the association between immunoglobulin (Ig)G below the lower limit of normal and serious infections.

Among the 757 analyzed patients (ocrelizumab, n = 375; interferon β-1a, n = 382), 67% of patients remained on treatment for over 9 years (ocrelizumab, 69%; interferon β-1a, 65%). Over the 9 years of treatment, rates of adverse events, serious adverse effects, serious infections and malignancies remained low. In the double blinded period and open label extension over 9 years, 1.8% (12 out of 668) of patients reported serious infections during periods of IgG below the lower limit of normal, with comparable types, characteristics and treatment outcomes to the overall serious infection profile.

Cerqueira et al noted, "the benefits and risks of highly effective therapy as first-line treatment early in RMS should inform evidence-based decisions, to improve patient outcomes compared with escalating from low efficacy treatments."¹

The 2 OPERA trials were conducted between August 2011 and April 2015 and included patients with RMS diagnosed using the 2010 revised McDonald criteria, randomized from 307 total sites across 56 countries. Overall, the baseline demographics and disease characteristics were similar for patients randomized to interferon β-1a vs ocrelizumab (mean age, 37.2 [standard deviation (SD), 9.2] vs 37.1 [SD, 9.2] years; 552 [66.6%] vs 541 women [65.4%]).

After completion of the 96-week controlled treatment period, most patients participated in the open-label extension phase of the OPERA studies and had their EDDS scores used to confirm potential initial increase of disability (IID) events that occurred at the end of the controlled period. Also, researchers conducted an analysis on a post-hoc subgroup in addition to the analysis of the overall IIT population.

In each treatment group, the few patients who experienced 12-week or 24-week composite CDA without fulfilling either definition of composite PIRA or composite RAW were more frequent with interferon β-1a treatment (14 of 829 [1.7%] and 8 of 829 [1.0%], respectively) compared with ocrelizumab treatment (3 of 827 [0.4%] and 2 of 827 [0.2%], respectively).

Since 2017, ocrelizumab has been approved by FDA for the treatment of primary progressive MS and relapsing MS. In late April 2020, the treatment had its supplemental applications review accepted by both the FDA and EMA for those with relapsing or primary progressive MS. As for interferon β-1a, the FDA approved updated prescribing information for the treatment in early April 2023 that included the removal of contraindications for pregnancy.²

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REFERENCES
1. Cerqueira J, Berthele A, Cree B, et al. Long-Term Treatment With First-Line Ocrelizumab in Patients With Early RMS: 9-Year OPERA Subgroup Analysis. Presented at: 2023 AAN Annual Meeting; April 22-27, Boston, Massachusetts. Abstract 002.
2. US FDA and EMA accept applications for Roche’s OCREVUS (ocrelizumab) shorter 2-hour infusion time. News Release. Basel, Switzerland: Genentech; Published April 20, 2020. Accessed April 24, 2023. globenewswire.com/news-