Efficacy and safety of ublituximab for relapsing multiple sclerosis patients: current evidence and expert opinion

Ublituximab, a newly launched anti-CD20 monoclonal antibody, represents a substantial advancement in the treatment landscape for relapsing multiple sclerosis (RMS). Its unique glycoengineered design enhances antibody-dependent cellular cytotoxicity, enabling rapid and effective B-cell depletion. Phase III randomized controlled trials ULTIMATE I and II confirmed superior efficacy of ublituximab over teriflunomide, achieving substantial reductions in annualized relapse rates, near-complete suppression of gadolinium-enhancing T1 lesions and new/enlarging T2-hyperintense white matter lesions, as well as higher rates of no evidence of disease activity 3. Safety data indicate that ublituximab is generally well tolerated, with mild, manageable infusion-related reactions as the most common adverse event. Its streamlined infusion protocol, requiring maintenance doses administered in just 1 h twice a year, provides a practical solution to the clinical and logistical challenges of MS management. Its rapid B-cell depletion, high efficacy, and convenient twice-yearly short infusion regimen make it particularly suitable for treatment-naïve patients with high disease activity who may benefit from early and robust disease control as well as for those who have experienced suboptimal responses, poor tolerability, or safety concerns with prior disease-modifying therapies. Although ublituximab shows great promise and five-year data are already available, further research is required to fully explore its potential in limiting disability progression and neurodegeneration, as well as to confirm its long-term safety. Real-world evidence, extended follow-ups, and comprehensive biomarker assessment specific to MS-related pathology will be essential to confirm its efficacy and optimize RMS patients’ management. This review synthesizes discussions from two meetings of Italian Neurologists held in 2024 and 2025, focusing on efficacy and safety data of ublituximab, and providing a comprehensive and in-depth analysis of its current and future role in RMS treatment.