Immunomodulatory therapies for relapsing-remitting multiple sclerosis: monoclonal antibodies, currently approved and in testing

Abstract

Relapsing-remitting multiple sclerosis (RRMS), a CNS inflammatory demyelinating disease, is one of the most prevalent causes of chronic disability in young adults. Studies of the disease pathogenesis have identified multiple therapeutic targets. The number of approved disease modifying therapies has almost doubled within the past 5 years, which creates a challenge for medical professionals to stay abreast of their use in everyday practice. This manuscript provides an overview of available injectable, oral, and intravenous therapies for RRMS, and offers guidance in selecting an appropriate therapy. Focus is on the recently approved and emerging monoclonal antibody therapies, because they offer more selective and superior therapeutic efficacy compared with injectable and oral disease modifying therapies. We discuss the outlook for monoclonal antibodies and their role in RRMS treatment in the future.

The future of multiple sclerosis treatments

“…Approved therapies such as the humanized antibodies natalizumab, alemtuzumab [13] and daclizumab, and the currently less used, cytostatic agent mitoxantrone are more effective but their use is associated with safety concerns. These drugs are administered parenterally and can have potentially severe side effects [e.g.…”

“…Natalizumab is a humanized recombinant monoclonal antibody directed against α4-integrin [13]. Natalizumab interferes with leukocyte migration from the peripheral blood into the CNS by preventing its binding via α4-integrin to the vascular cell adhesion molecule (VCAM) on endothelial cells [13].…”

“…Natalizumab interferes with leukocyte migration from the peripheral blood into the CNS by preventing its binding via α4-integrin to the vascular cell adhesion molecule (VCAM) on endothelial cells [13]. This step has an impact on CNS inflammation as it blocks the adhesion and subsequent migration of lymphocytes across the blood-brain barrier (BBB).…”

“…Alemtuzumab produces rapid and profound lymphopenia lasting for years via antibody-dependent cellular cytotoxicity [13]. Alemtuzumab was compared to IFNβ-1a administered subcutaneously three times a week in two phase III trials of RRMS [24,25].…”