A randomized blinded trial of combination therapy with cyclophosphamide in                 patients with active multiple sclerosis on interferon beta

Smith, Derek R.; Weinstock‐Guttman, Bianca; Cohen, Jeffrey A.; Wei, Xing‐Chang; Gutmann, Christine; Bakshi, Rohit; Olek, Michael J.; Stone, Lael A.; Greenberg, Steven J.; Stuart, David; Orav, John; Stuart, William H.; Weiner, H L

doi:10.1191/1352458505ms1210oa

Cited by 79 publications

(31 citation statements)

References 37 publications

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“…We observed that over 50% of patients with over 1 year of follow-up after the cessation of therapy continued to experience frequent relapses and required additional second-line treatments, suggesting that cyclophosphamide treatment did not induce a permanent suppression of the inflammatory process in this cohort of pediatric MS patients. Our results may differ from observations in adults 1 because of the selection of a particularly active pediatric MS population, or may be due to key differences in the immunologic response in children compared to adults, a hypothesis which requires further exploration.…”

Section: Figure Clinical Scores Precyclophosphamide and Postcyclophoscontrasting

confidence: 56%

“…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.…”

mentioning

confidence: 99%

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Cyclophosphamide therapy in pediatric multiple sclerosis

Makhani

Gorman²,

Branson³

et al. 2009

Neurology

120

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Section: Figure Clinical Scores Precyclophosphamide and Postcyclophoscontrasting

confidence: 56%

mentioning

confidence: 99%

Cyclophosphamide therapy in pediatric multiple sclerosis

Makhani

Gorman²,

Branson³

et al. 2009

Neurology

120

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“…Although well-designed trials have failed to conclusively demonstrate the efficacy of cyclophosphamide monotherapy, it is possible that combining cyclophosphamide, IFNb, and other agents may be an option for patients failing previous therapy and with limited treatment options. Data from a randomized, single-blinded, placebo-controlled, multicenter trial combining monthly cyclophosphamide and corticosteroids with IFNb indicate that this combination has some efficacy in reducing clinical relapses and MRI lesions [Smith et al 2005].…”

Section: Cyclophosphamidementioning

confidence: 99%

Chemotherapeutics in the treatment of multiple sclerosis

Kieseier

Jeffery

2010

Ther Adv Neurol Disord

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Abstract:The likely pathogenic mechanisms of multiple sclerosis (MS) provide a sound rationale for investigating the efficacy of drugs possessing immunosuppressive or immunomodulatory properties. With proven efficacy, safety and tolerability, interferon beta formulations and glatiramer acetate have become the mainstay of initial treatment for patients with relapsing forms of MS. More recently, natalizumab, a humanized monoclonal antibody (mAb) against the cellular adhesion molecule a4-integrin, has been employed for patients with an inadequate response or lack of tolerability to an alternate MS therapy, or as initial therapy for patients with severe disease. Various agents initially developed for oncological indications, either as chemotherapeutics or mAbs, may also have current or future uses in MS treatment. Mitoxantrone is currently the only chemotherapeutic agent approved for treatment of MS in the United States, while in parts of Europe azathioprine is approved and widely used for MS treatment. Other chemotherapeutics that have been tested in MS to date include cyclophosphamide, methotrexate, cladribine, and the mAbs alemtuzumab and rituximab. While there has been varying evidence of efficacy for these compounds, each appears to be associated with serious risks that require careful consideration and management. Given the risks that have been demonstrated for available chemotherapeutic agents and while long-term postmarketing safety data are still not available for those agents in development, it seems prudent to carefully assess the possible use of chemotherapeutics in the treatment of MS. A thorough riskbenefit analysis is becoming increasingly important in the assessment of therapeutic options for this disabling disease.

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“…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].…”

Section: Cyclophosphamidementioning

confidence: 99%

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

Brenton

Banwell

2016

Neurotherapeutics

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Acquired pediatric demyelinating diseases manifest acutely with optic neuritis, transverse myelitis, acute disseminated encephalomyelitis, or with various other acute deficits in focal or polyfocal areas of the central nervous system. Patients may experience a monophasic illness (as in the case of acute disseminated encephalomyelitis) or one that may manifest as a chronic, relapsing disease [e.g., multiple sclerosis (MS)]. The diagnosis of pediatric MS and other demyelinating disorders of childhood has been facilitated by consensus statements regarding diagnostic definitions. Treatment of pediatric MS has been modeled after data obtained from clinical trials in adult-onset MS. There are now an increasing number of new therapeutic agents for MS, and many will be formally studied for use in pediatric patients. There are important efficacy and safety concerns regarding the use of these therapies in children and young adults. This review will discuss acute management as well as chronic immunotherapies in acquired pediatric demyelination.

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A randomized blinded trial of combination therapy with cyclophosphamide in patients with active multiple sclerosis on interferon beta

Abstract: Combination therapy with CY/MP and IFNbeta-Ia decreased the number of Gd+ lesions and slowed clinical activity in patients with previously active disease on IFNbeta alone.

Cited by 79 publications

References 37 publications

Cyclophosphamide therapy in pediatric multiple sclerosis

Cyclophosphamide therapy in pediatric multiple sclerosis

Chemotherapeutics in the treatment of multiple sclerosis

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

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