Disease Modifying Agents

National recommended practice guidelines advocate early immunomodulating treatment to slow disease progression and help prevent irreversible neurological damage. Pharmacological management of this complex disease also involves treating acute attacks, managing symptoms, and monitoring interactions among medications, and between the disease process and the medical therapy.

The National MS Society Medical Advisory Board supports early intervention with disease modifying drugs to prevent relapses. Studies show that early relapses can cause permanent axonal damage and destruction of myelin. The Medical Advisory Board recommends that therapy with a disease-modifying drug should be started as soon as a diagnosis of relapsing-remitting MS is made, and that therapy should be continued indefinitely unless there is a clear lack of benefit, intolerable side effects, or until a better therapy is found.


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Early use of disease-modifying drugs can slow disease progression and prevent MS relapses.

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FDA approved disease modifying medications used to treat relapsing and/or progressive forms of MS:

Mitoxantrone (Novantrone®), is an approved disease modifying agent used to treat relapsing remitting and/or progressive forms of MS.

   
Generic/Brand Mechanism of Action Administration Contraindications Adverse reactions Warning
dimethyl
fumarate
TECFIDERA® Induction of nuclear factor 2 (Nrf2) antioxidant response pathway, the primary cellular defense against the cytotoxic effects of oxidative stress? PO, intact capsule

* Hypersensitivity to dimethyl fumurate
* Progressive multifocal leukoencephalopathy
* Hepatic disease
* Breast feeding

Leukopenia, leukoencephalopathy, angioedema, anaphylactoid reactions, eosinaphilia, elevated hepatic enzymes, ABD pain, DNV, rash, pruritus  
teriflunomide Aubagio® Pyrimidine synthesis inhibitor that reduces proliferation of peripheral T&B cells, reducing the concentration of activated lymphocytes in the CNS as well as reduced inflammatory phosphlipid synthesis? Oral pill once a day

* Hypersensitivity to teriflunomide,
* Alcoholism, hepatic disease, immunosupression.
* Agranulocytosis, chemotherapy, infection, thrombocytopenia, tuberculosis,
* Vaccination with live vaccines
* Eosinophilic pneumonia, pneumonitis, pulmonary disease, pulmonary fibrosis, sarcoidosis.
* Hypertention, diabetes mellitus
* Reproductive risk (Male & Female)
* Breast feeding

Renal failure, hepatic failure, pancytopenia , Stevens-Johnson syndrome, erythema multiforme, anaphylactoid reactions, hyperkalemia, myocardial infarction, pancreatiti, pulmonary fibrosis, eosinophilic pneumonia, fetal death, teratogenesis Black Box Warning
peginterferon beta-1a Plegridy Promotes oligodendrocyte survival, differentiation and axonal recovery by suppressing T-cells associated demyelination and inhibits pro-inflammatory cytokines? Promotes formation of anti-inflammatory cytokines. Inhibits T-cell migration across the blood-brain barrier? Subcutaneous

*Hypersensitivity to natural or recombinant interferon beta or peginterferon
*Alcoholism, hepatic disease, hepatitis, jaundice
*Depression, psychosis, suicidal ideation
*Seizure disorder
*Angina, cardiac arrhythmias, cardiac disease, heart failure, myocardial infarction
*Bone marrow suppression, autoimmune disease, thyroid disease
*Pregnancy, breast feeding
*Hemolytic-uremic syndrome, thrombotic thrombocytopenic purpura

* Injection site reactions
* Influenzalike illness
* Nausea
* Depression

 
interferon beta-1a Avonex® Intramuscular and subcutaneous

*Albumin hypersensitivity, latex hypersensity, hamster protein hypersensitivity
*Latex hyperse

* Liver failure, cardiac failure
* Headache
* Flu-like symptoms
* Depression

 
interferon beta-1a Betaseron® Subcutaneous Pregnancy, heart failure, albumin or latex hypersensitivity, breast feeding, depression, immunosuppression,

* Liver failure, cardiac failure
* Headache
* Flu-like symptoms
* Depression

 
glatiramer acetate Copaxone® Affects antigen-presenting cells such as monocytes and dendritic cells causing alteration in cytokine secretion by CD4+ and CD8+ T-cells? Intravenous/Subcutaneous Mannitol hypersensitivity, immunosuppression, infection, pregnancy, breast feeding Adverse reactions include injection site reactions, vasodilatation, chest pain, asthenia, infection, pain, nausea, arthralgia, anxiety, and hypertonia.  
natalizumab Tysabri® Natalizumab is a monoclonal antibody thought to reduce demyelination by interferring with adhesion molecules that facilitate migration T-lymphocytes across the blood brain barrier. IV infusion Progressive multifocal leukoencephalopathy, hypersensitivity, HIV, immunosupression, organ transplant, infection, leukemia Headache, fatigue, arthralgia, urinary tract infection, lower respiratory tract infection, gastroenteritis, vaginitis, depression, pain in extremity, abdominal discomfort, diarrhea, rash Black Box Warning
mitoxantrone Novantrone Antineoplastic DNA-reactive agent that intercalates into deoxyribonucleic acid (DNA) forming crosslinks and strand breaks. It also interferes with ribonucleic acid (RNA) and is a potent inhibitor of topoisomerase II, an enzyme responsible for uncoiling and repairing damaged DNA. IV infusion Preexisting cardiac disease, myelosuppression, hepatic disease, pregnancy, breast feeding.

Neutropenia, GI bleeding renal failure, heart failure, seizures, new primary malignancy, pulmonary edema anaphylactoid reactions, intracranial bleeding, pancytopenia, cardiomyopathy, tissue necrosis

 

Black Box warning
fingolimod Gilenya May act by reducing the number of circulating lymphocytes by inhibiting lymphocyte migration out of lymph nodes Oral capsule Hypersensitivity to fingolimod, Recent or current MI, stroke, heart failure Headache, myalgia, diarrhea, back pain, abnormal liver tests, and cough. Rarely: death or bradyarrhythmia and atrioventricular block at treatment initiation, infections, macular edema, respiratory effects, hepatic effects, and fetal risk FDA Warning

Although these drugs are not a cure for MS, they have each been shown to slow or modify the course of the disease. Tysabri and Novantrone have significant negative side effects and risks; please view the black box information. Gilenya has recently undergone an FDA safety review following reports of death and serious side effects.

Other immunosuppressive agents such as azathioprine (Imuran ®), cladribine (Leustatin ®), cyclophosphamide (Cytoxan ®), and methotrexate are also used for progressive forms of MS. As these agents are used to treat cancer, they are used in lower doses in MS therapy. However, patients may experience side effects such as hair loss and nausea and may be at risk for long-term side effects including sterility, cardiotoxicity, and liver toxicity.

 


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