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

Background Studies evaluating interferon beta (IFN beta) for multiple sclerosis (MS) showed only partial efficacy. In many patients, IFN beta does not halt relapses or disability progression. One strategy to potentially enhance efficacy is to combine IFN beta 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 IFN beta-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 IFN beta-1a 30 mu g intramuscularly (IM) once weekly, IFN beta-1a 30 mu g IM once weekly plus AZA 50 mg orally once daily, or IFN beta-1a 30 mu g 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 IFN beta-1a, 0.91 for IFN beta-1a plus AZA, and 0.73 for combination. The cumulative probability of sustained disability progression was 16.8% for IFN beta-1a, 20.7% for IFN beta-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 IFN beta-1a alone (+30.3%, P < 0.05). Groups had similar safety profiles. Conclusion In IFN beta-naive patients with early active RRMS, combination treatment did not show superiority over IFN beta-1a monotherapy. Multiple Sclerosis 2009; 15: 965-976. http://msj.sagepub.com