Immunosuppression with high-dose I.V. cyclophosphamide and acth in progressive multiple sclerosis

Carter, Jonathan L.; Az, Scottsdale; Dawson, David M.; Fallis, Robert J.; Hafler, David A.; Stazzone, Lynn; Weiner, Howard L.

doi:10.1016/0165-5728(87)90173-1

Cited by 14 publications

(18 citation statements)

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“…The Kaiser-Permanente Medical Care Program designed to evaluate the effects of intensive immunosuppression in MS showed modest benefits to the treatment but demonstrated the safety of outpatient CTX administration [21]. Carter et al showed that high-dose iv CTX and ACTH treatment regimen was well tolerated and favourably affected the course of chronic progressive MS, but some forms of maintenance treatment or re-treatment were requested for persistent stabilisation of disease [1]. The NorthEastern Cooperative Treatment Group reported a benefit from CTX boosters, but the positive clinical effects disappeared in 36 months.…”

Section: Discussionmentioning

confidence: 99%

“…Cyclophosphamide (CTX) is an alkylating agent related to nitrogen mustards used in treatment of neoplastic and non-neoplastic immune-mediated inflammatory diseases [19,20]. Its anti-inflammatory and immunosuppressive effects have been utilized to treat selected cases of multiple sclerosis with progressive and worsening course without obtaining a general agreement on the efficacy of this drug in modifying the course of the disease [1,4,5,6,8,9,14]. However literature data suggest that CTX is efficacious in MS when inflammation predominates over the degenerative process in the CNS and JON 1857 ■ Abstract The aim of the present study was to evaluate the efficacy of the combination of cyclophosphamide (CTX) and interferon beta (IFN β) in a group of relapsing remitting (RR) multiple sclerosis (MS) patients who experienced treatment failure during IFN β therapy.…”

Section: Introductionmentioning

confidence: 99%

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

et al. 2005

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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).

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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

et al. 2005

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“…Infections were defined "major" when accompanied by sepsis requiring intravenous antibiotics that prolonged the hospital course and/or caused significant morbidity. Infection were "minor" when requiring oral antibiotic therapy but not prolonging the hospital course or causing morbidity [17]. Major infections occurred in Group B (three cases of broncopneumonia) and in Group C (one case of broncopneumonia and one case with urinary sepsis).…”

Section: Fig 1 Clinical Evolution Of Patients Mean Changes In Edssmentioning

confidence: 97%

Cyclophosphamide in chronic progressive multiple sclerosis: a comparative study

Mantia¹,

Eoli²,

Salmaggi³

et al. 1998

Ital J Neuro Sci

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No effective treatment is presently available for progressive multiple sclerosis (MS). Cyclophosphamide (CFX), a cytotoxic immunosuppressive drug widely used in systemic dysimmune diseases, has been proposed for the treatment of multiple sclerosis with different schedules and controversial results. To evaluate the safety and clinical efficacy of CFX, we compared three different treatment schedules in patients with progressive MS: induction followed by bimonthly boosters for one year (17 patients); bimonthly boosters for one year without previous induction (15 patients); and monthly boosters for one year (21 patients). Survival analysis showed that the percentage of stable patients was significantly higher in the first and third treatment schedule groups. Myelotoxicity occurred in patients treated with induction and boosters (Group A). A high incidence of broncopneumonia was observed in patients undergoing the second treatment schedule (Group B). No major effects were observed in patients treated with monthly boosters (Group C). Response to treatment was limited to secondary progressive form. This study suggests that monthly treatment with CFX might be safely administered in progressive MS patients; its clinical efficacy must be confirmed by an appropriately designed clinical trial.

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“…Its anti-inflammatory and immunosuppressive effects have been used to treat selected cases of multiple sclerosis with progressive and worsening course without obtaining general agreement on the efficacy of this drug in modifying the course of the disease [1,5,6,8,9,19,21].…”

Section: Introductionmentioning

confidence: 99%

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

et al. 2004

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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.

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Immunosuppression with high-dose I.V. cyclophosphamide and acth in progressive multiple sclerosis

Cited by 14 publications

References 0 publications

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

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

Cyclophosphamide in chronic progressive multiple sclerosis: a comparative study

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

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