Treatment of fulminant multiple sclerosis with intravenous cyclophosphamide

BACKGROUND- The role of intravenous (IV) cyclophosphamide (CTX) for patients with progressive multiple sclerosis (MS) remains controversial, despite numerous controlled and uncontrolled clinical trials. OBJECTIVE- To present the results of open label treatment with CTX and intravenous methylprednisolone (MP) in 17 consecutive patients with corticosteroid-resistant, fulminant MS. METHOD- Open-label, nonblind, noncontrolled consecutive series of patients meeting the following criteria were treated with CTX and MP. Fulminant MS was defined as objectively documented, continuous deterioration by ≥1.5 points on the Kurtzke Expanded Disability Status Scale (EDSS) for ≥ 3 months. Corticosteroid resistance was defined as continued deterioration for 2 months after high-dose IV MP. After completion of the CTX/MP treatment protocol, all patients were subsequently treated with maintenance immunotherapy at the discretion of their treating neurologist. Each patient was followed by a single neurologist, who determined the EDSS according to a standard protocol at successive visits. RESULTS- Baseline EDSS scores at the time of CTX/MP treatment ranged from 6.0 to 8.5. There were no serious complications of treatment. Follow-up time ranged from 12 to 24 months (median 24 months, mean 22 months). At 12 months, 13 of 17 (75.5%) patients were stable or improved by ≥1.0 EDSS point. At 24 months, 9 of 13 (69%) of patients were stable or improved. CONCLUSION- This consecutive case series suggests that CTX/MP represents an effective therapeutic option for those rare MS patients with a fulminant progressive course who are refractory to corticosteroid therapy. The limitations related to the uncontrolled nature of the study and comparisons with other CTX studies are discussed.