Mitoxantrone versus cyclophosphamide in secondary-progressive multiple sclerosis

Abstract

Fifty secondary progressive multiple sclerosis (SPMS) patients who had lost one or more EDSS points in the prior two years were selected to receive either cyclophosphamide (25 patients, 13 females, 12 males, F/M = 1.08; mean age: 42.4 years; mean disease duration: 13.3 years; mean EDSS at study entry: 5.7) or mitoxantrone (25 patients, 14 females, 11 males, F/M = 1.27; mean age: 38.2 years; mean disease duration: 11.5 years; mean EDSS at study entry: 5.5). SPMS patients were treated for two years with clinical evaluation (relapse rate, disability progression) every three months and radiological imaging (conventional magnetic resonance imaging) before therapy initiation and at the end of the first and second years of therapy. Safety profile and costs of the two therapeutic protocols were also analysed. In terms of clinical and radiological measures the drugs exerted a quite identical effect on both, and produced a significant reduction in both relapse rate (mitoxantrone Mito): p = 0.001, cyclophosphamide (Cy): p = 0.003) and disability progression (Mito: p = 0.01; Cy: p = 0.01). Subgroups of mitoxantrone- and cyclophosphamide-responding patients were identified (14/25 and 17/25, respectively) and were characterized by a significantly shorter duration of the secondary progressive phase of the disease. In these subgroups, the improvement in the EDSS score at the end of therapy was highly significant (p<0.0001 for Mito, p = 0.0004 for Cy). The safety profiles of both drugs were acceptable; however, the Cy-based therapy protocol was significantly less expensive. We conclude that Cy should be considered as a therapeutic option in rapidly deteriorating SPMS patients.

Basic and escalating immunomodulatory treatments in multiple sclerosis: Current therapeutic recommendations

“…Similarly, add-on therapy with cyclophosphamide [98] and mitoxantrone [99] still has not been satisfactorily been investigated. In a small, open-labeled trial with parallel administration of either mitoxantrone or cyclophosphamide, the two medications were observed to have about equivalent efficacy on clinical and MRI parameters in SPMS patients but the statistical power of the study was low [100].…”

Cyclophosphamide therapy in pediatric multiple sclerosis

“…Cyclophosphamide has been shown to be effective in relapse rate reduction 1,2 and in control of MRI lesion accrual 1,3 ; however, effects in delaying disease progression have been variable. [4][5][6][7] Several studies have suggested that cyclophosphamide treatment may be most beneficial in younger adult patients, [7][8][9] and in patients with early secondary progressive MS. 6,7,10 MS onset before the age of 18 years is estimated at 2.7%-10.5% [11][12][13] of all patients. Children experience more frequent relapses than adults, suggesting a highly inflammatory disease.…”

Current Theories for Multiple Sclerosis Pathogenesis and Treatment

“…In situations where all other avenues have been exhausted and disease continues to progress at an unusually rapid rate, physicians may prescribe the chemotherapy drugs mitoxantrone or cyclophosphamide (Neuhaus et al, 2006;Perini et al, 2006;Rinaldi et al, 2009;Stuve et al, 2004;Theys et al, 1981). These drugs are often considered as final options due to their potent immunosuppressive and other serious effects.…”