This Article Full Text (PDF) All Versions of this Article: 1352458509105229v1 15/8/965    most recent References Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Add to Saved Citations Download to citation manager Request Permissions Request Reprints Add to My Marked Citations Citing Articles Citing Articles via Scopus Google Scholar Articles by Havrdova, E Articles by Horakova, D PubMed PubMed Citation Articles by Havrdova, E Articles by Horakova, D Social Bookmarking                         What's this?

Randomized study of interferon beta-1a, low-dose azathioprine, and low-dose corticosteroids in multiple sclerosis

Department of Neurology, Charles University in Prague, First Faculty of Medicine, Prague, Czech Republic eva.havrdova{at}gmail.com

R Zivadinov

Department of Neurology, Buffalo Neuroimaging Analysis Center, State University of New York at Buffalo, Buffalo, NY, USA

J Krasensky

Department of Radiology, Charles University in Prague, First Faculty of Medicine, Prague, Czech Republic

MG Dwyer

Department of Neurology, Buffalo Neuroimaging Analysis Center, State University of New York at Buffalo, Buffalo, NY, USA

I Novakova

Department of Neurology, Charles University in Prague, First Faculty of Medicine, Prague, Czech Republic

O Dolezal

Department of Neurology, Charles University in Prague, First Faculty of Medicine, Prague, Czech Republic

V Ticha

Department of Neurology, Charles University in Prague, First Faculty of Medicine, Prague, Czech Republic

L Dusek

Center of Biostatistics and Analyses, Faculty of Medicine and Faculty of Sciences, Masaryk University, Brno, Czech Republic

E Houzvickova

Department of Neurology, Charles University in Prague, Second Faculty of Medicine, Prague, Czech Republic

JL Cox

Department of Neurology, Buffalo Neuroimaging Analysis Center, State University of New York at Buffalo, Buffalo, NY, USA

N Bergsland

Department of Neurology, Buffalo Neuroimaging Analysis Center, State University of New York at Buffalo, Buffalo, NY, USA

S Hussein

Department of Neurology, Buffalo Neuroimaging Analysis Center, State University of New York at Buffalo, Buffalo, NY, USA

A Svobodnik

Center of Biostatistics and Analyses, Faculty of Medicine and Faculty of Sciences, Masaryk University, Brno, Czech Republic

Z Seidl

Department of Radiology, Charles University in Prague, First Faculty of Medicine, Prague, Czech Republic

M Vaneckova

Department of Radiology, Charles University in Prague, First Faculty of Medicine, Prague, Czech Republic

D Horakova

Department of Neurology, Charles University in Prague, First Faculty of Medicine, Prague, Czech Republic

Background

Studies evaluating interferon beta (IFNβ) for multiple sclerosis (MS) showed only partial efficacy. In many patients, IFNβ does not halt relapses or disability progression. One strategy to potentially enhance efficacy is to combine IFNβ with classical immunosuppressive agents, such as azathioprine (AZA) or corticosteroids, commonly used for other autoimmune disorders.

Objective

The Avonex–Steroids–Azathioprine study was placebo-controlled trial and evaluated efficacy of IFNβ-1a alone and combined with low-dose AZA alone or low-dose AZA and low-dose corticosteroids as initial therapy.

Methods

A total of 181 patients with relapsing–remitting MS (RRMS) were randomized to receive IFNβ-1a 30 µg intramuscularly (IM) once weekly, IFNβ-1a 30 µg IM once weekly plus AZA 50 mg orally once daily, or IFNβ-1a 30 µg IM once weekly plus AZA 50 mg orally once daily plus prednisone 10 mg orally every other day. The primary end point was annualized relapse rate (ARR) at 2 years. Patients were eligible for enrollment in a 3-year extension.

Results

At 2 years, adjusted ARR was 1.05 for IFNβ-1a, 0.91 for IFNβ-1a plus AZA, and 0.73 for combination. The cumulative probability of sustained disability progression was 16.8% for IFNβ-1a, 20.7% for IFNβ-1a plus AZA, and 17.5% for combination. There were no statistically significant differences among groups for either measure at 2 and 5 years. Percent T2 lesion volume change at 2 years was significantly lower for combination (+14.5%) versus IFNβ-1a alone (+30.3%, P < 0.05). Groups had similar safety profiles.

Conclusion

In IFNβ-naïve patients with early active RRMS, combination treatment did not show superiority over IFNβ-1a monotherapy.

Key Words: azathioprine • beta-interferon • corticosteroids • disease modifying therapies • placebo-controlled

This version was published on August 1, 2009

Multiple Sclerosis, Vol. 15, No. 8, 965-976 (2009)
DOI: 10.1177/1352458509105229


CiteULike    Complore    Connotea    Del.icio.us    Digg    Reddit    Technorati    Twitter    What's this?