To assess the efficacy and safety of ocrelizumab over 3 years in patients with relapsing-remitting multiple sclerosis (RRMS) who rolled over from CASTING (NCT02861014) to LIBERTO (NCT03599245).

The Phase IIIb CASTING study evaluated the efficacy and safety of ocrelizumab in patients with RRMS with a suboptimal response to ≥6 months treatment with one or two prior disease-modifying therapies (DMTs). LIBERTO is a long-term extension study, in which eligible CASTING patients from participating countries could enroll.

Patients deemed by the treating neurologist as having a positive benefit-risk ratio at the end of the CASTING 96-week treatment period rolled over to LIBERTO and continued intravenous ocrelizumab
600mg every 24 weeks. Efficacy endpoints included no evidence of disease activity (NEDA; absence of protocol-defined relapses, 24-week confirmed disability progression, contrast-enhancing T1-weighted and new/enlarging T2-weighted lesions), with MRI rebaselining at CASTING Week 8. Safety outcomes included incidence/nature of adverse events (AEs).

As of October 12, 2020, 439/680 CASTING patients rolled over to LIBERTO. NEDA was observed in 82.6% of patients from baseline to Year 1 (n/N=549/665), 87.0% of patients from Year 1 to Year 2 (n/N=571/656) and 82.5% of patients from Year 2 to Year 3 (n/N=235/285). Over the 3-year period, 59.4% of patients had NEDA (n/N=190/320). Mean (SD) Expanded Disability Status Scale score was 2.09 (1.06) at CASTING baseline and 2.16 (1.48) at Year 3. Annualized relapse rate remained low (Year 1, 0.07; Year 2, 0.05; Year 3, 0.05). Overall, 92.3% of patients reported AEs (n/N=405/439) and 8.4% of patients reported serious AEs (n/N=37/439). Four patients from LIBERTO discontinued due to AEs (0.9%); one death occurred in CASTING.

Patients with a suboptimal response to one or two prior DMTs who switched to ocrelizumab responded consistently well to ocrelizumab treatment over 3 years, based on clinical and MRI measures. No new safety signals were observed.