Ofatumumab for relapsing forms of multiple sclerosis.

Abstract

In recent years, B cells have been extensively studied as a therapeutic target in multiple sclerosis (MS). Particularly, anti-CD20 monoclonal antibodies (MAbs) such as rituximab or ocrelizumab have proven to be effective in treating various forms of MS. Ofatumumab, a second-generation anti-CD20 IgG1κ fully human MAb, binds to a different, membrane-proximal epitope of CD20 compared with other anti-CD20 MAbs, thus ensuring a slower dissociation rate. This results in dose-dependent B-cell depletion mainly exerted through a mechanism of complement-dependent cytotoxicity. The repletion kinetic is faster than that of rituximab or ocrelizumab. Ofatumumab is the first approved drug for relapsing forms of MS that is administered via subcutaneous injection every 4 weeks. Two phase II and two phase III clinical trials have shown that it is effective in reducing the annualized relapse rate and clinical disability worsening, as well as in suppressing magnetic resonance imaging (MRI) disease activity. The safety profile of the drug has proven to be favorable, with good tolerability and low immunogenic risk. Moreover, the subcutaneous injection grants an easier way of administration. The current evidence on ofatumumab efficacy and safety is reviewed in the present article.