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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.


Oral Administration
Generic/Brand		Mechanism of Action	Contraindications	Adverse reactions
dimethyl fumarate	Tecfidera	Induction of nuclear factor 2 (Nrf2), the primary cellular defense against the cytotoxic effects of oxidative stress?	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?	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
fingolimod	Gilenya	Inhibits lymphocyte release from the lymph nodes, decreasing the number of lymphocytes available to migrate to the CNS.	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
cladribine	Mavenclad	Interferes with DNA synthesis and repair by incorporation into DNA, resulting in sustained reduction of circulating T and B lymphocytes implicated in the pathogenesis of MS	Current malignancy, pregnant women and persons of reproductive potential, HIV, chronic infections (eg, hepatitis, tuberculosis).	Upper respiratory infection, headache, low white blood cell count
siponimod	Mayzent	Inhibits lymphocyte release from the lymph nodes, decreasing the number of lymphocytes available to infiltrate CNS.	CYP2C93/3 genotype increases cardiovascular risk. Verify vaccination status, increased infection risk.	Headache, hypertension, and transaminase elevation; macular edema
Injectable Treatment
Generic/Brand		Mechanism of Action	Contraindications	Adverse reactions
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?	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		Albumin hypersensitivity, latex hypersensity, hamster protein hypersensitivity Latex hyperse	Liver failure, cardiac failure Headache Flu-like symptoms Depression
interferon beta-1a	Betaseron		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?	Mannitol hypersensitivity, immunosuppression, infection, pregnancy, breast feeding	Adverse reactions include injection site reactions, vasodilatation, chest pain, asthenia, infection, pain, nausea, arthralgia, anxiety, and hypertonia.
Intravenous Infusion
Generic/Brand		Mechanism of Action	Contraindications	Adverse reactions
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.	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
ocrelizumab	Ocrevus	Monoclonal antibody that inhibits replication of the CD20-positive B lymphocyte cell lines, that damage nerve cells and the myelin sheaths	Active hepatitis B virus infection, serious infusion reaction.	Pruritus, rash, urticaria, erythema, bronchospasm, throat irritation, oropharyngeal pain, dyspnea, pharyngeal or laryngeal edema, flushing, hypotension, pyrexia, fatigue, headache, dizziness, nausea, and tachycardia.
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.	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
alemtuzumab	Lemtrada	Monoclonal antibody that binds to CD52 on T and B lymphocytes. Binding causes lysis of the lymphocytes reducing T-cells infiltration to the CNS.	Active tuberculosis, inactive tuberculosis, Listeria monocytogenes infection, HIV, shingles, herpes simplex infection, chronic hepatitis B, Chronic Hepatitis C, protozoa infection.	Immune thrombocytopenia, autoimmunity, infusion reactions, thyroid disorders, malignancies, glomerular nephropathies, etc.

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