Review ArticleReview Article
Open Access

The use of immune modulating drugs for the treatment of multiple sclerosis

Fahd A. Al-Khamis
Neurosciences Journal January 2016, 21 (1) 4-9; DOI: https://doi.org/10.17712/nsj.2016.1.20150252

Article Figures & Data

Figures

  • Figure 1
    Figure 1

    Schematic representation of the mechanisms of action of 4 immune modulating drugs currently used in the treatment of multiple sclerosis (MS). In the circulatory system Alemtuzumab targets CD52, primarily expressed on T and B-cells and monocytes (Mono)/macrophages (MØ) resulting in their depletion. Also in the circulatory system, Natalizumab binds to a4b1-integrin on T-cells, B-cells and Mono/MØ resulting in their reduced migration across the blood-brain barrier (BBB) into the central nervous system (CNS). Fingolimod blocks the release of activated lymphocytes from lymph nodes by targeting sphingosin-1-phosphate receptors. In the CNS, dimethyl fumarate (DMF) switches cytokine production of T-cells that have migrated into the CNS towards a Th2 profile and enhances NRF2, which has immune regulatory and cytoprotective effects on oligodendrocytes, neurons, and glial cells.

Tables

  • Table 1

    Comparisons of the effects of various medications on multiple sclerosis patients.

    EffectsImmune modulating drugs
    AlemtuzumabDimethyl fumarate (DMF)NatalizumabFingolimod
    TargetDecreases the number of T-cells, B-cells and monocytes/macrophages expressing CD52Promotes anti-inflammatory responses within the CNS by activating Th2 responsesInhibits lymphocyte migration through BBB into the CNS by targeting α4β1-integrinInhibits activated lymphocytes from leaving lymph nodes by targeting S1P-receptors
    B-cellsDecreasesDecreasesDecreasesDecreases
    T-cellsDecreasesDecreasesDecreasesDecreases
    Pro-inflammatory cytokinesDecreasesDecreasesDecreasesDecreases
    Anti-inflammatory cytokinesNCDIncreasesIncreasesNCD
    Side effects (common)Headache, pyrexia, nausea, pruritus insomnia, fatigue, chest discomfort and dyspneaCough or hoarseness, feeling of warmth, fever or chills, lower back or side pain, painful or difficult urination, redness of the face, neck, arms, and occasionally, upper chestCough, difficulty with swallowing, dizziness, fast heartbeat, puffiness or swelling of the eyelids or around the eyes, face, lips, or tongue, shortness of breath, skin rash, hives, or itching, tightness in the chest, unusual tiredness or weaknessDiarrhea, coughing, headaches, hair loss, depression, muscle weakness, dry, itchy skin
    Side effects (rare)Respiratory and urinary tract infections, herpetic infections (mucocutaneous herpes simplex and herpes zoster), autoimmune AELymphopenia, leucopenia, WBC decreased, Ketones in urine, vitamin D decreased, cardiovascular, gastrointestinal, dermatologic, hepatic, hypersensitivityPML, pharyngitis, urinary tract infection, urticaria, cephalgia, dizziness, nausea, vomiting, arthralgia, fever, and rigidity.Bradyarrhythmia and atrioventricular blocks, macular edema, elevated liver function, increased risk of respiratory tract infections, urinary tract infections, regional herpes virus infections and hypertension
    Cognition, depression and fatigueImprovesNCDNCDNCD
    Quality of lifeImprovesImprovesImprovesImproves

    • BBB - blood-brain barrier, ND - no conclusive data, PML - progressive multifocal leukoencephalopathy, SIP - sphingosin-1-phosphate, WBC - white blood cells, AE - adverse events

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