Cyclophosphamide Treatment of MS: Current Therapeutic Approaches and Treatment Regimens

Immunosuppression and immunotherapy have developed as the primary mode of therapy for multiple sclerosis (MS) and are most effective in active, relapsing stages of the disease. Cyclophosphamide has been used in the treatment of MS for over 40 years. The effectiveness of cyclophosphamide and its ability to stabilize MS patients has been suggested in many studies. Cyclophosphamide has selective effects on the immune response, including the suppression of Th1/Th17 responses and the enhancement of cells secreting anti-inflammatory cytokines such as interleukin (IL) IL-4, IL-10 and TGF-b. Different regimens have been developed fosssssssssr the use of cyclophosphamide in MS, from intermittent outpatient pulse therapy that is analogous to protocols used in lupus nephritis, to very high-dose inpatient regimens. Cyclophosphamide has also been used to treat paediatric MS. Like most immunomodulatory drugs, cyclophosphamide has limited, if any efficacy in primary progressive MS, or stages of secondary progressive MS with slow clinical deterioration, in the absence of relapses or inflammatory changes (gadolinium enhancement) on magnetic resonance imaging. Cyclophosphamide is used in relapsing or actively progressive MS as second-line therapy in patients unresponsive to interferon beta or glatiramer acetate who are not candidates for natalizumab.