Current Treatment Strategies for Multiple Sclerosis - Efficacy Versus Neurological Adverse Effects

Abstract

Recent years have broadened the spectrum of therapeutic strategies and specific agents for treatment of multiple sclerosis (MS). While immune-modulating drugs remain the first-line agents for MS predominantly due to their benign safety profile, our growing understanding of key processes in initiation and progression of MS has pioneered development of new agents with specific targets. One concept of these novel drugs is to hamper migration of immune cells towards the affected central nervous system (CNS). The first oral drug approved for MS therapy, fingolimod inhibits egress of lymphocytes from lymph nodes; the monoclonal antibody natalizumab prevents inflammatory CNS infiltration by blocking required adhesion molecules. The second concept is to deplete T cells and/or B cells from the peripheral circulation using highly specific monoclonal antibodies such as alemtuzumab (anti-CD52) or rituximab/ocrelizumab (anti-CD20). All of these novel, highly effective agents are a substantial improvement in our therapeutic armamentarium; however, they have in common to potentially lower the abundance of immune cells within the CNS, thereby collaterally affecting immune surveillance within this well-controlled compartment. In this review, we aim to critically evaluate the risk/benefit ratio of therapeutic strategies in treatment of MS with a specific focus on infectious neurological side effects.

MAGNIMS consensus guidelines on the use of MRI in multiple sclerosis—establishing disease prognosis and monitoring patients

“…In general, MRI has three major tasks in this context: detection of persistent disease activity, comorbid ities (such as vascular or neoplastic disorders) and adverse effects (including opportunistic infections). 7,93 The crucial role of MRI in pharmacovigilance is made evident by the case of natalizumab, a recombinant human ized monoclonal antibody against α4 integrin. 94 This treatment for MS is highly effective, but is associated with progressive multifocal leukoencephalopathy (PML), a potentially life threatening adverse effect.…”

Role of Integrin Alpha4 in Drug Resistance of Leukemia

“…Natalizumab, which is almost fully humanized, has been available in the clinic for treatment of relapsing–remitting multiple sclerosis as well as of complicated refractory inflammatory bowel disease with very high efficaciousness and for the most part good safety and tolerability. Long-term treatment has been associated in some patients with induction of neutralizing antibodies against the few remaining murine amino acid residues of the antibody, a scenario presenting as mild infusion-associated serum sickness and loss of efficacy (83). Infrequently, JC-virus-associated progressive multifocal leukoencephalopathy (PML) has been described after prolonged use, a complication, which is associated with a poor prognosis despite aggressive plasmapheresis (84).…”

A discrete-choice experiment to determine patient preferences for injectable multiple sclerosis treatments in Germany

“…First-line treatment for MS in Germany has evolved over the past 3 years to now include oral treatments such as dimethyl fumarate and teriflunomide [Warnke et al 2013;Weber et al 2012]. However, historically, the mainstay of disease-modifying treatments (DMTs) for MS are injectable immunomodulatory drugs [Patti, 2010;Wingerchuk and Carter, 2014].…”