Targeted therapy of multiple sclerosis: real-world experience with divozilimab

Abstract

Introduction. Anti-B-cell therapy that prevents clonal expansion of B cells expressing CD20 is a significant achievement in the pharmacotherapy of multiple sclerosis (MS). Randomized studies have shown high efficacy of monoclonal antibodies (mAb), confirmed by a reduction in the annualized relapse rate (ARR), MRI activity, and the risk of disability progression. Divozilimab (DIV) is a humanized afucosylated anti-CD20 mAb with a modified Fc fragment that provides high effector activity. The aim is to evaluate the efficacy and safety of DIV in patients with various MS phenotypes in real-world clinical practice. Materials and methods. The prospective study included 43 patients: 24 with rapidly progressive MS, 9 with highly active MS, and 10 with secondary progressive MS with relapses. All received DIV therapy for 6–12 months. We assessed ARR, MRI activity (lesions with contrast enhancement (T1-Gd+), new/enlarged T2 lesions), changes in the Expanded Disability Status Scale (EDSS), CD19+ B-cell levels, and the safety profile. Data were analyzed before therapy, at 6 months, and at 12 months of treatment. Results. Over 12 months of therapy, ARR decreased from 1.3 to 0.03; the proportion of patients without T1-Gd+ lesions increased from 27.9% to 100%, and new T2 lesions were detected in 6.1%. The median EDSS decreased from 3.0 [2.0; 3.5] to 2.5 [2.0; 3.0]. Profound depletion of CD19+ B cells was noted (0% [0.0; 0.2]); NEDA-3 (No Evidence of Disease Activity-3) status was achieved in 84.9%. Adverse events were limited to mild/moderate infusion reactions (30.2% at the first infusion), and no serious adverse events were recorded. Conclusion. DIV provides rapid and sustained suppression of clinical and MRI activity in MS with pronounced B-cell depletion and a favorable safety profile, justifying its early use in patients with high disease activity