The Canadian cooperative trial of cyclophosphamide and plasma exchange in progressive multiple sclerosis. The Canadian Cooperative Multiple Sclerosis Study Group.
To find out whether non-specific immunosuppression is beneficial in multiple sclerosis (MS) a randomised, placebo-controlled, single-masked trial was carried out in nine university centres. 168 patients with clinically or laboratory-supported definite MS in progressive phase (deterioration by at least 1.0 on the expanded disability status scale [EDSS] in the previous year) were randomised to receive intravenous cyclophosphamide and oral prednisone (n = 55); daily oral cyclophosphamide, alternate day prednisone (22 weeks), and weekly plasma exchange (20 weeks) (n = 57); or placebo medications and sham plasma exchange (n = 56). All patients were followed for at least 12 months (mean 30.4 months) by a monitoring neurologist, who was aware of treatment allocation, and an evaluating neurologist, who was not. The primary analysis was a comparison of rates of treatment failure (worsening of evaluating neurologist's assessment of EDSS by 1.0 or more on two consecutive 6-monthly assessments). There were no significant differences among the groups in this primary analysis (19 [35%] treatment failures with cyclophosphamide; 18 [32%] with plasma exchange; 16 [29%] with placebo). Nor were there any differences in the proportions improved, stabilised, or worsened at each 6 month assessment or in the mean change in the EDSS at the final assessment (0.81 cyclophosphamide; 0.69 plasma exchange; 0.69 placebo). A slight trend favouring the plasma exchange group at 12-24 months of follow-up was not sustained at the final assessment. This study fails to confirm previous reports that immunosuppressive treatments result in stabilisation or improvement in progressive MS.
D000328:Adult; D002170:Canada; D003131:Combined Modality Therapy; D003520:Cyclophosphamide / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D004334:Drug Administration Schedule; D004359:Drug Therapy, Combination; D005069:Evaluation Studies as Topic; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008297:Male; D009103:Multiple Sclerosis / Q000401:mortality / Q000503:physiopathology / Q000628:therapy*; D010951:Plasma Exchange / Q000009:adverse effects; D011241:Prednisone / Q000008:administration & dosage / Q000627:therapeutic use; D016019:Survival Analysis
D003520:Cyclophosphamide; D011241:Prednisone