Multiple sclerosis (MS) is one of the most common causes of neurological disability in young adults, occurring more frequently in women than men. The development of anti-cluster of differentiation 20 (CD20) monoclonal antibodies (mAbs) in recent years has significantly changed the way we treat MS. Compared to older standards of care, such as chemotherapy and immunosuppressive drugs, anti-CD20 mAbs have been shown to be more effective in treating MS with fewer side effects.
Data have shown that B cells play a crucial role in the pathogenesis of MS via antigen-driven autoantibody responses and the cross-regulation of T-helper cells. CD20 is a protein that is expressed on the surface of B cells. Since B cells express the surface molecule CD20 at all points of differentiation, they provide a specific target for mAbs and are used to treat certain types of cancer and autoimmune disorders, including MS.
In people living with MS, the immune system mistakenly attacks the myelin sheath, a protective layer that surrounds nerve fibers in the central nervous system. This attack can cause inflammation and damage to the myelin sheath, leading to the development of various symptoms such as muscle weakness, vision problems, and issues with coordination and balance.
Anti-CD20 antibodies work by targeting and destroying B cells, which play a role in the immune system's attack on the myelin sheath. By targeting and destroying these cells, anti-CD20 antibodies may help to reduce the inflammation and damage to the myelin sheath and improve symptoms of MS.
There are several anti-CD20 mAbs used for the treatment of MS, including ocrelizumab, ofatumumab, ublituximab, and rituximab. Each drug has a unique mechanism of action and safety profile and distinct monitoring requirements. These therapies have been shown to deplete circulating B cells significantly for a certain amount of time, and they may be used in combination with other medications to treat MS.
Ocrelizumab, a humanized anti-CD20 mAb administered by intravenous (IV) infusion, was approved in March 2017 by the US Food and Drug Administration (FDA) and is the first proven treatment to reduce disability progression in both primary progressive MS and relapsing MS. Interestingly, ocrelizumab binds to a CD20 epitope that overlaps partially with the epitope to which rituximab binds.
Ofatumumab is the first fully human anti-CD20 mAb and was approved by the FDA in August 2020 for treating relapsing forms of MS. The approval was on the basis of data from the phase 3 ASCLEPIOS I and II trials, which compared ofatumumab with teriflunomide, an oral agent that reduces the activity of proliferating T lymphocytes and B lymphocytes, mitigating the overall inflammatory response in MS. Subcutaneous ofatumumab demonstrated better efficacy than oral teriflunomide in reducing the annualized relapse rate in patients with MS.
Ublituximab was recently approved by the FDA for treatment of relapsing forms of MS, including relapsing-remitting MS and active secondary progressive MS . Ublituximab works much like other anti-CD20 antibodies; however, it has been glycoengineered so that certain altered sugar molecules attached to the antibody increase its effectiveness.