Drugs Targeting CD20 in Multiple Sclerosis: Pharmacology, Efficacy, Safety, and Tolerability

Abstract

Currently, there are four monoclonal antibodies (mAbs) that target the cluster of differentiation (CD) 20 receptor available to treat multiple sclerosis (MS): rituximab, ocrelizumab, ofatumumab, and ublituximab. B-cell depletion therapy has changed the therapeutic landscape of MS through robust efficacy on clinical manifestations and MRI lesion activity, and the currently available anti-CD20 mAb therapies for use in MS are a cornerstone of highly effective disease-modifying treatment. Ocrelizumab is currently the only therapy with regulatory approval for primary progressive MS. There are currently few data regarding the relative efficacy of these therapies, though several clinical trials are ongoing. Safety concerns applicable to this class of therapeutics relate primarily to immunogenicity and mechanism of action, and include infusion-related or injection-related reactions, development of hypogammaglobulinemia (leading to increased infection and malignancy risk), and decreased vaccine response. Exploration of alternative dose/dosing schedules might be an effective strategy for mitigating these risks. Future development of biosimilar medications might make these therapies more readily available. Although anti-CD20 mAb therapies have led to significant improvements in disease outcomes, CNS-penetrant therapies are still needed to more effectively address the compartmentalized inflammation thought to play an important role in disability progression.

Hypogammaglobulinaemia during rituximab treatment in multiple sclerosis: A Swedish cohort study

“…The data from our cohort indicate a lower rate of IgG decline compared with the NMOSD and RA studies, which possibly in part could be explained by dose reductions and extended infusion intervals at Swedish centres [2,31,32]. In the rituximab studies for RA, concomitant medication with methotrexate and oral steroids can contribute to this risk [8].…”

“…se), off-label use started more than 10 years ago with treatment protocols adapted from rheumatology (1000-2000 mg every 6-24 months). Gradually, lower doses and prolonged intervals were introduced with evidence of sustained efficiency [2,[31][32][33].…”