Stabilization of rapidly worsening multiple sclerosis for 36 months in patients treated with interferon beta plus cyclophosphamide followed by interferon beta

Abstract

Cyclophosphamide (CTX) is an alkylating agent related to nitrogen mustards whose anti-inflammatory and immunosuppressive effects have been utilised to treat selected cases of multiple sclerosis with a progressive and worsening course. To halt the progression of disease in patients refractory to disease modifying drugs CTX has been given, and several open-label studies have recently shown clinical benefits. In a previous study we demonstrated the effectiveness of a combination of IV monthly pulses of CTX and interferon beta (IFN-beta) in 10 patients with "rapidly transitional" form of multiple sclerosis characterised by severe and frequent attacks and rapid progression of disability. The present study reports the clinical and MRI follow-up 36 months after the discontinuation of CTX showing the maintenance of the results obtained in relapse rate (p<0.001), EDSS (p<0.001), T2 MRI total lesion load (p<0.001) and T2 lesions number (p<0.001) compared to the pre-treatment period. These encouraging findings and the absence of significant recorded side effects affirm that the association of CTX plus interferon-beta is amenable, safe and can be recommended in rapidly worsening MS patients.

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

“…Differently from our previous studies the population of patients here investigated were RR with an active form of disease, and poor responders to IFN β treatment. This sample could be more representative of RR MS population than the rapidly transitional groups previously described [29,30]. Thus the present results could suggest a therapeutic option for RR MS in the earlier stages of the disease when inflammatory activity is prominent.…”

“…In previous studies we demonstrated the effectiveness of a combination of IV monthly pulses of CTX and IFN β in patients with transitional MS, characterized by severe and frequent attacks and rapid progression of disability [29]. On the basis of the results obtained with the combination therapy on this group of patients and after the analysis of follow-up data which showed the maintenance of the benefits after 54 months [30], we decided to enlarge the combination treatment to those MS patients who did not seem to obtain any benefit from treatment with IFN β. The aim of the present study was to evaluate the efficacy and the safety of the combination treatment in a group of active RR MS patients previously treated with INF β.…”

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.…”

Role of Immunosuppressive Therapy for the Treatment of Multiple Sclerosis

“…Studies generally show that the onset of MRI effect is within 1-5 months [21]. Cyclophosphamide has also been used successfully in combination with IFN [22][23][24]. Despite different dosing schedules trials with cyclophosphamide have been consistent in showing that patients respond best if they are younger, have a shorter disease duration, and still have relapses or evidence of recent MRI activity [25,26].…”