Efficacy and Safety of Patients With Relapsing Multiple Sclerosis Switching to Ocrelizumab Due to Suboptimal Treatment Response: Results of the 4-Year CASTING–LIBERTO Trial

Background: Almost 75% of patients with relapsing multiple sclerosis (pwRMS) with suboptimal response to other disease-modifying therapies (DMTs) showed no evidence of disease activity (NEDA-3) when treated with ocrelizumab in a large single-arm multicentre trial over 2 years. We aimed to assess the 4-year effectiveness and safety of ocrelizumab in pwRMS who entered a 2-year extension trial. Methods: PwRMS completing CASTING were eligible to rollover into LIBERTO if available in the country of residence. PwRMS received ocrelizumab every 24 weeks; the same frequency was used for clinical assessments. Primary endpoint was the proportion of patients who had NEDA-3 over 4 years. Safety was assessed by rate and nature of adverse events (AEs). Results: A total of 439 pwRMS rolled over to LIBERTO, of which 68.1% completed the study; most patients discontinued from LIBERTO due to country-specific changes in reimbursement but most remained on ocrelizumab outside the trial. Over 4 years, 79.5% of patients showed no 24-week confirmed disability progression, 87.5% no relapses, and 90.0% no radiological activity. A total of 65.6% of patients (n = 290) showed NEDA-3, with the proportion of patients achieving NEDA-3 yearly remaining above 84.8%. Over 4 years, infections (72.9% of patients) and infusion-related reactions (44.2%) were the most reported AEs. Serious AEs were reported in 9.3% of patients. Five (1.1%) patients discontinued due to AEs. Conclusions: Findings suggest that switching to ocrelizumab is safe for patients with early RRMS and suboptimal response to previous DMTs, resulting in significant and durable control of disease activity. Trial Registration: LIBERTO (NCT03599245), extension study to CASTING (NCT02861014); first patient enrolled 12.07.2018; https://clinicaltrials.gov/study/NCT03599245. CHORDS (NCT02637856), ENSEMBLE (NCT03085810).