An open-label trial of combination therapy with interferon β-1a and oral methotrexate in MS

Calabresi, Peter A.; Wilterdink, Janet L; Rogg, Jeffrey; Mills, P.; Webb, Adam; Whartenby, Katharine A.

doi:10.1212/wnl.58.2.314

Cited by 82 publications

(38 citation statements)

References 10 publications

(14 reference statements)

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“…Immunosuppressor drugs (cyclophosphamide, and AZA) combined with plasma exchange failed in secondary progressive MS [7, 8]. Experimentation with the use of immunosuppressor drugs (cyclophosphamide [9], methotrexate [10], and AZA [11]) combined with IFN-β has also produced interesting findings; recently, Markovic–Plese et al [12]have reported an open-label study demonstrating a 69% reduction in the number of contrast-enhancing lesions during the combination therapy (AZA/IFN-β 1b ) in 6 patients. Controlled studies of combined AZA and IFN-β treatment are not yet available.…”

Section: Introductionmentioning

confidence: 99%

Azathioprine and Interferon β<sub>1a</sub> in Relapsing-Remitting Multiple Sclerosis Patients: Increasing Efficacy of Combined Treatment

Lus¹,

Romano²,

Scuotto³

et al. 2004

Eur Neurol

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Current treatments of relapsing-remitting multiple sclerosis (RRMS) with immunosuppressive or immunomodulatory drugs have been shown to modify the course of the disease in a significative number of patients. However, in many cases, the response to either interferon β (IFN-β) or azathioprine (AZA) treatments was not satisfactory and new therapeutic approaches are needed. We studied clinical and MRI efficacy, safety and tolerance of AZA and IFN-β_1a combined therapy in 23 patients with clinically definite RRMS, who had not previously been responsive to either monotherapies. Our cases were divided into three subgroups: 8 previously untreated patients (subgroup A) with at least 2 years of natural course of the disease, 8 patients (subgroup B) previously treated with AZA for 2 years and 7 patients (subgroup C) previously treated with IFN-β_1a for 2 years. The baseline Expanded Disability Status Scale (EDSS) ranged from 2 to 4 in all subgroups. All patients completed 2 years of combined treatment with a dose of AZA adjusted to reduce lymphocyte count down to 1,000 ± 100/µl in association with IFN-β_1a at a dose of 6 MIU every other day. The mean number of relapses during the combined treatment period was significantly lower than that observed before combined therapy in all the three subgroups. Also, the mean ΔEDSS score was significantly lower during combined treatment than in monotherapy in subgroups B and C. Moreover, after 2 years of combined treatment, the number of new T₁ hypointense lesions, the number and volume of proton density/T₂ hyperintense lesions and the gadolinium enhancement of T₁ hypointense lesions were significantly lower than before combined treatment. After 2 years of treatment, this combination therapy appears to be safe and well tolerated and no serious side effects were reported. Despite some limitations of our study design, the information regarding efficacy, safety and tolerance of the association of AZA and IFN-β is most encouraging.

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Section: Introductionmentioning

confidence: 99%

Azathioprine and Interferon β<sub>1a</sub> in Relapsing-Remitting Multiple Sclerosis Patients: Increasing Efficacy of Combined Treatment

Lus¹,

Romano²,

Scuotto³

et al. 2004

Eur Neurol

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“…An open-label study has been performed to evaluate combination therapy with weekly oral methotrexate and β-interferon 1a im in patients who continued to experience relapses with β-interferon 1a im monotherapy [2]. The results were consistent with a reduction in disease activity measured on MRI and in relapse rates following addition of methotrexate.…”

Section: ■ Other Combinations With β β-Interferonsmentioning

confidence: 72%

Rationale and experience with combination therapies in multiple sclerosis

Boggild

2006

J Neurol

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“…In an open-label trial, Calabresi et al [70] added 20 mg of methotrexate to intramuscular IFN-beta1a for 6 months in 15 relapsing patients and found a 44 % reduction in number of gadolinium-enhancing lesions when compared with baseline scans of patients on IFN-beta-1a alone. Cohen et al [71] randomized patients with breakthrough disease on intramuscular IFN-beta-1a to combination treatment with either oral methotrexate 20 mg weekly, methylprednisolone 1 g intravenously bimonthly, or both.…”

Section: Trial Effects and Usementioning

confidence: 99%