In MS: Immunosuppression is passé.

IMPORTANCE: Prolonged and significant alterations of the immune system by immunosuppression makes multiple sclerosis (MS) patients susceptible to opportunistic infections and malignancies over long periods of treatment. OBSERVATIONS: A reasonable clinical and practical definition of immunosuppression is a temporary or permanent alteration of the body's immune system and subsequent lack of ability to fight infections and malignancies. Immunosurveillance is the sine qua non of the immune system. Immunosurveillance is the constant process by which the immune system looks for and recognizes foreign pathogens such as bacteria and viruses or pre-cancerous or cancerous cells in the body. Immunomodulation (a decrease or increase in pitch or tone - in this case a decrease) maintains immunosurveillance. Immunosuppression (quashing, stamping out) impedes immunosurveillance by one mechanism or another. Immunosuppressive agents need to be administered continually in order to maintain effectiveness. In contrast, immune reconstitution therapies (IRTs) are short course agents that are initially immunosuppressive but ultimately immunomodulatory and can provide significant decreased disease activity over time without retreatment. CONCLUSIONS AND RELEVANCE: The goal of disease modifying therapies in MS is effectiveness over long periods of time with minimal risk. The preservation, reduction or elimination of immunosurveillance should be an important consideration in deciding on the optimal disease modifying treatments (DMT) for an individual MS patient. IRTs have the advantage of providing long term control of disease activity with short term immunosuppression followed by long term immunomodulation without retreatment. For most MS patients with mild or modest disease activity, initial immunomodulation followed by IRT for breakthrough disease may be the best option. In MS, immunosuppression may be passé.