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).