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Combination Appears Safe in Relapsing-Remitting Multiple Sclerosis: Presented at AAN

By Jill Stein

SAN DIEGO, C.A. -- April 4, 2006 -- The combination of interferon beta 1-a (Avonex) and azathioprine for use in multiple sclerosis (MS) patients is safe and well tolerated and potentially effective, according to preliminary results presented here at the 58^th Annual Meeting of the American Academy of Neurology (AAN).

Jeffrey I. Greenstein, MD, director, Multiple Sclerosis Institute, Philadelphia, Pennsylvania, United States, and colleagues assessed the safety of the addition of azathioprine to intramuscular interferon beta 1-a in patients who were incompletely responsive to intramuscular interferon beta-1a and to determine if the combination would improve both clinical and magnetic resonance imaging (MRI) outcomes.

Dr. Greenstein presented the results of the 12-month, open-label safety study on April 4^th.

The study enrolled 12 patients with relapsing-remitting MS who had experienced at least 1 relapse in the prior 12 months while on interferon beta-1a alone. None of the 12 subjects had interferon neutralising antibodies. They received a combination of a 30-mcg intramuscular injection of interferon beta-1a plus 150 mg azathioprine orally each week.

"Although the currently approved therapies for the treatment of MS have proven efficacy in relapse reduction, and some of them slow disease progression, it is estimated that 50% to 70% of patients on monotherapy will experience ongoing disease activity," Dr. Greenstein observed. "Combination therapy, particularly the use of agents with different modes of action, may improve outcomes."

Interferon-beta therapy has pleiotropic immunomodulatory, anti-inflammatory, and antiviral effects. Potential effects in MS include reduction of matrix metalloproteinase activity, inhibition of proliferation, and enhanced secretion of interleukin-10, he said.

Azathioprine reduces cellular and humoral immunity by inducing T-cell apoptosis and inhibits T-cell/APC conjugation, producing immunosuppression.

Both agents have shown reductions in relapse rates in MS, he added.

In the trial, safety evaluations were performed at baseline and months 1, 2, 3, 6, 9, and 12.

Three subjects withdrew from the study because of nonadherence, limb fracture, and treatment-induced nausea. No significant haematologic or hepatic toxicity occurred.

At the 12-month evaluation, results showed that the annualised relapse rate was significantly decreased from baseline following treatment (1.4-0.3, P <.001). In addition, the number of gadolinium-positive lesions decreased from a mean of 3.3 to 0.5 (P <.0625).

Neither the Expanded Disability Status Score (EDSS) nor the Multiple Sclerosis Functional Composite or its components were significantly affected by combination therapy (P =.280; P =.190, respectively).

Dr. Greenstein said that larger trials of longer duration are needed to confirm the efficacy of the combination.

"Overall, the combination appears safe and well tolerated in patients with relapsing-remitting MS and potentially effective, with a significant effect on relapse rate and trends towards magnetic resonance imaging and disease improvement on both EDSS and MRI measures after treatment," Dr. Greenstein concluded.

The study was supported by Biogen Idec, Inc.


[Presentation title: A Safety Study of Interferon-Beta1a (Avonex) and Azathioprine in Breakthrough Disease in Relapsing-Remitting Multiple Sclerosis. Abstract P01.085]

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