Positive 4-year efficacy and safety data of ocrelizumab in early MS

Intense therapy with ocrelizumab in patients with early-stage relapsing-remitting multiple sclerosis (RRMS) showed clinical remission with MRI disease activity in most patients. There were no new safety signals.

Early treatment of MS has been shown to provide significant long-term benefits in terms of EDSS compared with delayed treatment. Ocrelizumab is a recombinant, humanised immunoglobulin (Ig) G1 monoclonal antibody that selectively targets CD20-expressing B cells. The single-arm ENSEMBLE trial (NCT03085810) evaluated the safety and efficacy of ocrelizumab in treatment-naive participants with early (≤3 years) RRMS [1]. Eligible participants were aged 18–55 years, had active disease, an EDSS score ≤3.5 and ≥1 clinical relapse(s) or signs of MRI activity in the 12 months before enrolment. The 678 participants received ocrelizumab 600 mg initially as 2 intravenous infusions of 300 mg 2 weeks apart and subsequently as a single 3.5-hour 600 mg infusion every 24 weeks for 192 weeks. Dr Robert Bermel (Cleveland Clinic, OH, USA) presented the efficacy and safety data after 4 years of treatment. Key endpoints were no evidence of disease activity (NEDA)-3, annualised relapse rate (ARR), mean change in EDSS from baseline, and safety.

The median age of participants was 31 years, the mean duration since diagnosis was 0.24 years, and the mean EDSS (SD) at baseline was 1.71 (0.95). At week 192, two-thirds of participants had NEDA (n=394/593: 66.4%), 77.9% showed no evidence of clinical activity, and 85.0% showed no disease activity on MRI. Furthermore, 90.9% of participants had no relapses, and 81.8% had no 24-week confirmed disability progression. Also, 90.6% and 90.4% of participants showed no T1-weighted contrast-enhancing lesions or T2-weighted lesions, respectively. The adjusted ARR was low, 0.020 (95% CI 0.015–0.027), and EDSS improved in 22.8%, remained stable in 59.3%, and worsened in 18.0% of participants.

The safety was consistent with the known profile of ocrelizumab, with no new or unexpected signals. Throughout the trial, 647 patients (95.4%) had an adverse event, whereby 105 (15.5%) participants presented with serious events and grade ≥3 events were observed in 21 (3.1%) participants. The 6 fatalities (0.6%) comprised 2 cases of COVID-19, 2 cases of COVID-19 pneumonia, 1 case of pneumonia, and 1 case of immune reconstitution inflammatory syndrome. Serious infections occurred in 6.9% of participants.

1. Bermel RA, et al. Low Disease Activity Over 4 Years of Ocrelizumab Therapy in Treatment-Naive Patients With Early-Stage Relapsing-Remitting Multiple Sclerosis; the Phase IIIb ENSEMBLE Study. S46.005, AAN 2023 Annual Meeting, 22–27 April, Boston, USA.

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Posted on 26 June 202325 March 2024