The combination of cyclophosphamide plus interferon beta as rescue therapy could be used to treat relapsing–remitting multiple sclerosis patients

Abstract

The aim of the present study was to evaluate the efficacy of the combination of cyclophosphamide (CTX) and interferon beta (IFN beta) in a group of relapsing remitting (RR) multiple sclerosis (MS) patients who experienced treatment failure during IFN beta therapy. It is the general experience that immunomodulatory agents (IMA) are only partially effective in RR patients. Recent data on the efficacy of immunosuppressive therapies for these patients are encouraging. The anti-inflammatory and immunosuppressive effects of CTX have been utilized to treat selected cases of multiple sclerosis with a progressive and worsening course as rescue therapy. Thirty RR MS patients with clinically defined MS who experienced treatment failure during IFN beta therapy (2 or more relapses per year or 1.5 EDSS point worsening in one year) were enrolled in the study and treated with CTX iv pulse therapy added to IFN beta and followed up for 24 months. As primary endpoints we evaluated the yearly relapse rate. We also evaluated the percentage of patients free of relapses and of EDSS variations. We analysed the results at one year before entry (T0: IFN beta alone), 12 (T1) and 24 (T2) months after entry. Brain MRI was performed at T0, at T1 and T2. The 30 RR patients who had experienced a high number of relapses (rr =1.4) at T0 showed a significant improvement in yearly relapse rate (rr = 0.4) at T1 and a further improvement (rr = 0.17) at T2 (p < 0.001). The percentage of patients free of relapse was 70% at T2 (p < 0.0001). EDSS score changed from 2.6+/-1.23 at T0 to 2.2 +/- 1.5 at T2, showing only a trend of improvement. No significant variation of MRI lesion load and no severe adverse events were recorded during the study. These data showed that the combination of CTX plus IFN beta halted the progression of disease in active and deteriorating MS patients suggesting the necessity of RCTs to test the efficacy of this combination therapy in active RRMS patients or in patients who experienced treatment failure in response to disease modifying drugs (DMDs).

Therapeutic Approach to the Management of Pediatric Demyelinating Disease: Multiple Sclerosis and Acute Disseminated Encephalomyelitis

“…Cyclophosphamide is typically infused monthly (with or without induction) and works as an immunosuppressing agent affecting cytokine expression (with pronounced effects on IL-12) along with T-cell and B-cell function [95]. In adults with RRMS, cyclophosphamide appears to reduce relapse rate and the accrual of new lesions on MRI [96,97] Fig. 2 Proposed algorithm for the approach to treating a pediatric patient with multiple sclerosis (MS) [40].…”

Cyclophosphamide therapy in pediatric multiple sclerosis

“…It is generally administered as monthly maintenance therapy, in some cases preceded by an induction course. 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.…”

Mitoxantrone versus cyclophosphamide in secondary-progressive multiple sclerosis

“…Monotherapy use of Mito or Cy [15,[19][20][21][22][23][24] or either used in combination with immunomodulatory agents [25][26][27] has considerably increased over the last years. Despite the risk of dramatic adverse events, like severe acute or delayed heart failure [28] and acute myeloid leukaemia [20][21][22][23][24][25][26][27][28][29][30], Mito has become, after approval by the FDA and EMEA, a first-line rescue therapy for RRMS patients who do not respond to IMA and for rapidly deteriorating SPMS [31][32][33][34].…”

“…Despite the risk of dramatic adverse events, like severe acute or delayed heart failure [28] and acute myeloid leukaemia [20][21][22][23][24][25][26][27][28][29][30], Mito has become, after approval by the FDA and EMEA, a first-line rescue therapy for RRMS patients who do not respond to IMA and for rapidly deteriorating SPMS [31][32][33][34]. Cy, although used in many MS Centres in Europe and the US [35], is not approved for MS and can be used in Italy only when informed consent is obtained.…”