To report 4-year efficacy and safety data of ocrelizumab in a subgroup of patients with early, high-activity relapsing-remitting multiple sclerosis (HA RRMS) from the ENSEMBLE study (NCT03085810) and to assess predictors of no evidence of disease activity (NEDA)-3 in the overall ENSEMBLE population.

ENSEMBLE was an open-label, single-arm Phase IIIb study evaluating the efficacy and safety of ocrelizumab in patients with early-stage RRMS; disease activity was minimal in most patients treated over the 4-year period.

Patients in the HA subgroup were treatment naive, aged 18–55 years, had active early-stage RRMS (duration ≤3 years), Expanded Disability Status Scale (EDSS) ≤3.5, ≥2 prior relapses and MRI activity in the year prior to screening. Patients received ocrelizumab 600 mg every 24 weeks for 192 weeks. Key endpoints included NEDA-3 (defined as no relapses, no 24-week [W] confirmed disability progression [CDP] and no MRI activity) and safety. Cox regression analysis for NEDA-3 predictors was performed in the overall population.

In the ENSEMBLE study, 29% (n=198/678) of patients had HA disease, with a median age of 30.0 years; duration since MS symptom onset, 0.71 years; duration since RRMS diagnosis, 0.24 years; mean baseline EDSS score (SD), 1.85 (0.95). At W192, 64.4% of patients (n=116/180) included in the HA disease subgroup analysis had NEDA, 90.6% had no relapses, 82.2% had no 24W-CDP and 83.9% had no MRI activity. No new or unexpected safety signals were observed. Cox regression analysis showed that older age at diagnosis in the overall ENSEMBLE population increased the risk of not achieving NEDA by 2% per year difference (p=0.016).

NEDA-3 rates and the safety profile of ocrelizumab in patients with HA RRMS were consistent with those previously reported for the overall ENSEMBLE population. Age at diagnosis can significantly impact the likelihood of reaching NEDA-3.