HOW TREATMENT WORKS

The goals of current MS treatment are to modulate or suppress the immune system and thus reduce the autoreactive activity and inflammation that results from such activity. To date there are six FDA approved treatments for MS. Four of these are self-injected medications that are currently considered first-line: three interferon beta products, and one glatiramer acetate. Second-line treatments are a monoclonal antibody: natalizumab and an immunosuppressant agent, mitoxantrone. Each treatment has an effect on the immune system and reduces the inflammation associated with multiple sclerosis. This effect translates into fewer relapses, less progression of disability and fewer inflammatory changes that are seen on MRI.

Interferon beta 1a and 1b are self-injected immunomodulating medications that work by reducing the ability of antigen-presenting cells to present antigen. Interferons occur naturally and have an important role in our response to viral infections. They reduce T-cell activation and proliferation. In addition, they reduce the enzyme production that disrupts the blood-brain barrier. They also reduce expression of the adhesion molecules necessary for adhesion of lymphocytes to the blood vessel endothelium. The result of this immunomodulation is fewer relapses, a delayed progression of disease, and the reduction of new areas of inflammation in the CNS. The potential adverse effects of interferon betas are elevation in hepatic enzymes, anemia, flulike symptoms, mood disorder, and injectionsite reactions.

Glatiramer acetate is also a self-injected immunomodulator but works by a different mechanism than the interferons. Glatiramer acetate is thought to work by inducing the immune system to be less inflammatory. This appears to be accomplished by inducing naïve T-cells to become activated as anti-inflammatory T-cells. These glatiramerinduced T-cells gain entry to the CNS and reduce the inflammation associated with MS by bystander suppression. In addition, there is some evidence that neuroprotective mechanisms are activated by the anti-inflammatory cells. The end result of this activity is the reduction in relapses, delay in progression, and reduction in inflammation within the CNS. The potential adverse effects associated with glatiramer acetate are injection-site reactions, which include lipoatrophy, and a rare brief post-injection reaction that can include symptoms such as flushing, tachycardia, dyspnea, weakness, chest tightness and nausea. Natalizumab is a monoclonal antibody that blocks the ability of lymphocytes to adhere to the endothelium of the blood brain-barrier and thus restricts their entry into the central nervous system. This “blockade” has the end result of reduction in relapses, delay in progression and the reduction in new CNS inflammation. Natalizumab has been associated with the development of progressive multifocal leukoencephalopathy, a rare infection of the CNS that is often fatal. In addition, other less serious infections are associated with natalizumab as well as infusion and allergic reactions.

Mitoxantrone is a powerful chemotherapeutic agent that reduces the number of inflammatory cells available to produce inflammation. This agent was studied in secondary-progressive MS patients and was found to delay progression of disease. It also reduces CNS inflammation and relapses. Adverse effects of mitoxantrone include lymphopenia, infections, cardiac damage, and increased risk for secondary leukemia.

Many additional immunomodulatory agents are in the MS treatment pipeline and each of them impacts the immune system in some way. It is important for nurses to understand the normal as well as abnormal immune system so that we can better understand the treatments for this complex disease. Effective treatments are available, and soon additional treatments will be part of our armamentarium. We will need to know how these drugs impact the immune system and the expected MS effect. We will also need to know the expected adverse effects, how to identify them, and how to help our patients manage these effects.