Minimal Disease Activity Seen With Ocrelizumab for Early RRMS Over 4 Years

After 4 years of ocrelizumab therapy, patients with early relapsing-remitting multiple sclerosis (RRMS) who were treatment-naive generally remained with low-level or no disease activity, without new or unexpected safety signals. These are the results of a study presented at the 2023 Consortium of Multiple Sclerosis Centers (CMSC) Annual Meeting, held from May 31 to June 3 in Aurora, Colorado.

In the open-label, single-arm, phase 3b ENSEMBLE study (ClinicalTrials.gov Identifier: NCT03085810), 678 patients (median age, 31) received 600 mg ocrelizumab every 24 weeks. On average, the patients had enrolled in the study approximately 1-year after symptom onset; and, they had a mean Expanded Disability Status Scale (EDSS) score of less than 2 at baseline.

A total of 593 patients completed the study. Of those patients, 66.4% had no evidence of disease activity following a week-8 re-baselining, ie, were without progression of disability or relapse, or magnetic resonance imaging (MRI) evidence of worsening.

Across the 4-year study period, of the entire cohort, 647 patients (95.4%) reported adverse events (AE), 15.5% of which were serious events. An AE graded 1-2 occurred in close to 76% of patients, while an AE graded 3 and 4 were reported for 17.3% and 1.5%. A total of 6 deaths occurred (4 due to COVID-19, 1 to inflammatory pathology during immune recovery, and 1 to pneumonia).

Further AE data were as follows:

• 510 infections (75.2%) in the study included 68 COVID-19 infections; 47 infections (6.9%) were serious, including 14 COVID-19 cases.
• Among 351 patients reporting infusion-related reactions, none was greater than Grade 3 (13 reactions), although 3 were considered serious.
• Of 34 malignancies (5%), 8 were serious.
• 21 patients (3.1%) discontinued therapy, and 11 (1.6%) modified or interrupted therapy, due to an AE.

Researchers concluded, “Low levels of disease activity and no new safety signals were observed in treatment-naive patients with early RRMS over 4 years of OCR [ocrelizumab] treatment in the ENSEMBLE study.”

Disclosures: Several study authors have declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of the author’s disclosures.