A randomized blinded trial of combination therapy with cyclophosphamide in patients with active multiple sclerosis on interferon beta

被引:54
作者
Smith, DR
Weinstock-Guttman, B
Cohen, JA
Wei, X
Gutmann, C
Bakshi, R
Olek, M
Stone, L
Greenberg, S
Stuart, D
Orav, J
Stuart, W
Weiner, H
机构
[1] Brigham & Womens Hosp, Dept Neurol, Boston, MA 02115 USA
[2] Brigham & Womens Hosp, Dept Epidemiol, Boston, MA 02115 USA
[3] Cleveland Clin, Dept Neurol, Cleveland, OH 44106 USA
[4] Buffalo Gen Hosp, Dept Neurol, Buffalo, NY 14203 USA
[5] Peachtree Neurol Clin, Atlanta, GA USA
关键词
brain atrophy; breakthrough disease; combination therapy; cyclophosphamide; cytotoxic agents; eosinophilia; eosinophils; glucocorticoids; IFN beta; IL-4; methylprednisolone; mitoxantrone; MRI; MS; natalizumab = antegren = tysabri; randomized clinical trial; RRMS; treatment failure;
D O I
10.1191/1352458505ms1210oa
中图分类号
R74 [神经病学与精神病学];
学科分类号
摘要
Objective: To evaluate the efficacy and safety of combination therapy with pulse cyclophosphamide given with methylprednisolone ( MP) and interferon beta (IFN beta)-1a in multiple sclerosis (MS) patients with active disease during IFN beta monotherapy. Methods: This was a randomized, single-blind, parallel-group, multicenter trial in MS patients with a history of active disease during IFNb treatment. Patients were randomized to either cyclophosphamide 800 mg/m(2) plus methylprednisolone 1 g IV (CY/MP) or methylprednisolone once a month for six months and then followed for an additional 18 months. All patients received three days of methylprednisolone 1 g IV at screening and 30 mcg IFN beta-1a IM weekly for the entire 24 months. The primary endpoint was change from baseline in the mean number of gadolinium-enhancing (Gd+) lesions. Secondary clinical endpoints included time to treatment failure. Results: Fifty-nine patients were randomized to treatment: 30 to CY/MP and 29 to MP. Change from baseline in the number of Gd+ lesions was significantly different between treatment groups at three ( P = 0.01), six ( P = 0.04) and 12 months ( P = 0.02), with fewer lesions in the CY/MP group. The cumulative rate of treatment failure was significantly lower in the CY/MP group compared with the MP group ( rate ratio = 0.30; 95% confidence interval, 0.12 - 0.75; P = 0.011). CY/MP treatment was well tolerated. Conclusion: Combination therapy with CY/MP and IFN beta-1a decreased the number of Gd+ lesions and slowed clinical activity in patients with previously active disease on IFN beta alone.
引用
收藏
页码:573 / 582
页数:10
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