Cyclophosphamide as second-line therapy in multiple sclerosis: benefits and risks.

Cyclophosphamide (Cy) is an alkylating agent used over the past 40 years to halt rapidly progressive forms of multiple sclerosis (MS). High doses of Cy produce marked immunosuppression and an anti-inflammatory immune deviation. Cy is most effective in young patients, with very active MS (frequent relapses, rapid accumulation of disability, and gad+ lesions on brain MRI). Monthly intravenous pulses of Cy for 1 year, followed by bimonthly pulses for the second year are a well-tolerated protocol in MS. Most side effects (mild alopecia, nausea and vomiting, and cystitis) are transient, dose dependent, and reversible. Permanent amenorrhoea and bladder cancer have rarely been described. As second-line therapy, Cy can be used in non-responders to IFN-beta or glatiramer acetate. As induction therapy, a short course (6-12 months) of Cy can precede immunomodulatory drugs in selected patients with an aggressive MS onset.