NEDA sustained for up to 10 years with ocrelizumab in treatment-naïve RMS

In approximately 9 of 10 treatment-naïve (TN) patients with relapsing MS (RMS) treated with ocrelizumab, either intravenous (IV) or subcutaneous (SC), no evidence of disease activity (NEDA-3) was maintained in any given year. Long-term safety data were reassuring, with infection rates decreasing over time and serious infection rates remaining low and stable [1].

These findings derive from long-term follow-up of the phase 3 OPERA I/II (NCT01247324/NCT01412333) [2], with up to 10 years of follow-up, and the phase 3 OCARINA II study (NCT05232825) [3], with 2 years of follow-up. Both studies enrolled TN patients with early RMS. In OPERA I/II, 603 participants were randomised to IV ocrelizumab, of whom 375 had been diagnosed with MS within the previous 2 years. In OCARINA II, 46 participants were randomised to SC ocrelizumab.

The primary efficacy endpoint was NEDA-3, defined as the absence of protocol-defined relapses, no 48-week confirmed disability progression (CDP48), and no MRI activity (no gadolinium-enhancing T1 lesions (Gd+ T1) and no new or enlarging T2 lesions. Event rates over the entire study period and safety were also evaluated.

Across both studies, approximately 9 of 10 participants achieved NEDA-3 in any given year. Efficacy appeared comparable between IV and SC formulations. Most participants remained free of relapses, CDP48, and MRI activity throughout the ocrelizumab treatment.

Over the entire follow-up period, corresponding to 4,547.8 patient-years in the IV group (10 years) and 95.8 patient-years in the SC group (2 years), the proportions of patients achieving key outcomes were as follows:

NEDA-3: 60.9% (IV) and 90.6% (SC);
No relapse: 75.0% (IV) and 97.8% (SC);
No CDP48: 83.4% (IV) and 98.1% (SC);
No Gd+ T1 lesions: 97.8% (IV) and 98.6% (SC);
No new or enlarging T2 lesions: 89.2% (IV) and 89.5% (SC).

Regarding safety, infection rates declined over time, while serious infections remained low and stable in both groups. In the IV group, infection rates per 100 patient-years were 90.5 at year 1, 68.0 at year 5, and 44.1 at year 10. Corresponding rates of serious infections were 0.68, 1.72 and 1.3 per 100 patient-years, respectively. In the SC group, infection rates decreased from 83.1 per 100 patient-years at year 1 to 38.0 at year 3; no serious infections were reported in this cohort.

Overall, these long-term data support sustained high efficacy and favourable safety profile of both IV and SC ocrelizumab in treatment-naïve patients with early RMS.

Newsome SD, et al. No Evidence of Disease Activity in treatment-naive people with relapsing multiple sclerosis treated with intravenous or subcutaneous ocrelizumab: Findings of the OPERA (10 Years) and OCARINA II (2 Years) studies. P125, ACTRIMS Congress 2026, 4–7 February, San Diego, California, USA.
Hauser SL, et al. N Engl J Med. 2017;376(3):221-234.
Newsome SD, et al. Neurology. 2025;104(9):e213574.