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

Mult Scler. 2009 Aug;15(8):965-76. doi: 10.1177/1352458509105229. Epub 2009 May 22.


Background: Studies evaluating interferon beta (IFNbeta) for multiple sclerosis (MS) showed only partial efficacy. In many patients, IFNbeta does not halt relapses or disability progression. One strategy to potentially enhance efficacy is to combine IFNbeta 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 IFNbeta-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 IFNbeta-1a 30 microg intramuscularly (IM) once weekly, IFNbeta-1a 30 microg IM once weekly plus AZA 50 mg orally once daily, or IFNbeta-1a 30 microg 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 IFNbeta-1a, 0.91 for IFNbeta-1a plus AZA, and 0.73 for combination. The cumulative probability of sustained disability progression was 16.8% for IFNbeta-1a, 20.7% for IFNbeta-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 IFNbeta-1a alone (+30.3%, P < 0.05). Groups had similar safety profiles.

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

Publication types

  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Administration, Oral
  • Adrenal Cortex Hormones / administration & dosage*
  • Adrenal Cortex Hormones / adverse effects
  • Atrophy
  • Azathioprine / administration & dosage*
  • Azathioprine / adverse effects
  • Brain / pathology
  • Disability Evaluation
  • Disease Progression
  • Double-Blind Method
  • Drug Administration Schedule
  • Drug Therapy, Combination
  • Humans
  • Immunologic Factors / administration & dosage*
  • Immunologic Factors / adverse effects
  • Immunosuppressive Agents / administration & dosage*
  • Immunosuppressive Agents / adverse effects
  • Injections, Intramuscular
  • Interferon beta-1a
  • Interferon-beta / administration & dosage*
  • Interferon-beta / adverse effects
  • Magnetic Resonance Imaging
  • Multiple Sclerosis, Relapsing-Remitting / diagnosis
  • Multiple Sclerosis, Relapsing-Remitting / drug therapy*
  • Prednisone / administration & dosage*
  • Prednisone / adverse effects
  • Prospective Studies
  • Recurrence
  • Time Factors
  • Treatment Outcome


  • Adrenal Cortex Hormones
  • Immunologic Factors
  • Immunosuppressive Agents
  • Interferon-beta
  • Azathioprine
  • Prednisone
  • Interferon beta-1a