Treatment of relapsing–remitting multiple sclerosis with high-dose cyclophosphamide induction followed by glatiramer acetate maintenance

Abstract

Background Previous studies have described stabilization of aggressive multiple sclerosis (MS) with one-time induction therapy with high-dose cyclophosphamide (HiCy). The long-term benefit of this stabilization followed by conventional therapy has not been explored. Objective The objective of this study was to evaluate the safety and clinical outcomes following treatment of relapsing–remitting MS with HiCy induction therapy followed by glatiramer acetate maintenance. Methods A retrospective review of a closely followed population of thirty two MS patients treated with HiCy (200mg/kg intravenous infusion over 4 days) followed by maintenance with glatiramer acetate was performed. Results Annualized relapse rate was reduced from 1.37 in the 2 years prior to treatment to 0.27 over a mean post-treatment follow-up period of 14 months (range 0.5–33.8). The projected probability of relapse-free survival at 2 years was 0.64 (95% CI 0.37–0.82). The projected probability of Expanded Disability Status Scale (EDSS) progression-free survival at 2 years was 0.77 (95% CI 0.43–0.92). The mean number of gadolinium-enhanced lesions was reduced from 0.86 (SD 1.6) at baseline to 0 at 12 months and 0.08 (SD 0.28) at 15–24 months. A total of 55% of patients had no evidence of disease activity in follow-up. Infectious complications occurred in 47% with no long-term morbidity and no deaths. Conclusions Induction therapy with HiCy followed by long-term maintenance with glatiramer acetate is well tolerated in patients with MS, and appears to be efficacious in reducing the risk of relapse, disability progression, and new MRI lesions.

Relapses in Multiple Sclerosis: Definition, Pathophysiology, Features, Imitators, and Treatment

“…Although there is not enough scientific evidence available, high-dose cyclophosphamide or rituximab can be evaluated in patients who are refractory to steroid and plasma exchange therapy or in those for whom these therapies cannot be performed (85,86).…”

Dynamics of B-Cell Populations in CSF and Blood in Patients Treated with a Combination of Rituximab and Mitoxantrone

“…Synergistic drug combinations of few relatively “strong” medications can potentially decrease the cumulative dose of any one medication and thus reduce some treatment associated risks. Such a combination could possibly be reserved as an escalation opportunity for patients with particularly active disease and poor prognostic factors [34], or as a preferable alternative to other induction approaches such as alemtuzumab [35], cladribine [4], high-dose cyclophosphamide (RevImmune) [36], and bone marrow transplantation.…”

Therapeutic Management of Severe Relapses in Multiple Sclerosis

“…Given the kinetics of such therapies, however, their primary effect is probably more of accelerating induction of immunosuppression to prevent subsequent relapse disease activity than acting as true acute rescue treatments for relapse. Myeloablative induction dosing of cyclophosphamide (i.e., 50 mg/kg/day for 4 days) has been shown in small studies in MS to lead to remission of disease activity and improvement in disability [67,68], and there are reports of the use of such strategies in children [69], although the risks of such therapy in this context require better characterization and such treatment is typically reserved for use in exceptional cases involving fulminant or tumefactive syndromes. Cyclophosphamide can also be given as an intravenous pulse of 500-800 mg/m 2 of body surface area every 3-4 weeks without inducing severe myeloablation, but this treatment strategy functions more as a relatively aggressive preventive immunosuppressive therapy and not as an acute Table 3.…”