Brief Alert

Interferon-beta Therapy in MS: Development of Neutralizing Antibodies

Source: Ross C, et al. Immunogenicity of interferon-beta in multiple sclerosis patients: Influence of preparation, dosage, dose frequency and route of administration. Ann Neurol 2000;48:706-712.

In this study from denmark, 754 patients starting on different preparations of interferon-beta (IFNb) were prospectively followed in a national protocol in which serum were collected at 0, 3, 6, 12, 18, and 24 months. These samples were then assayed for ability to bind IFN-b and neutralize the biological activity of IFNb in an antiviral neutralization assay. The IFNb preparations were Betaseron (IFNb-1b, 300 mg SC injection QOD), Avonex (IFNb-1a, 30 mcg IM injection Q weekly), or Rebif (IFNb-1a, 22 mcg SC injection 1-3 times weekly).

Ross and associates found that IFNb-1b preparations had a higher occurrence of binding and neutralizing antibodies by 12 months, compared to IFNb-1a. In addition, IFNb-1a was more likely to be immunogenic when given by subcutaneous vs. intramuscular injection, or when administered three times vs. one time weekly. Antibodies induced against one preparation also seemed to cross-react with other preparations.

Commentary

This study helps to define a potential concern with patients receiving long-term administration of recombinant human cytokines. Previous reports have indicated widely variable frequencies in neutralizing antibodies for patients on IFNb therapy. This study demonstrated that the frequencies are highly dependent on the type and specific conditions in the assays, so that it is helpful that all samples were tested under uniform conditions. In the United States, neutralizing assays are performed by Athena Diagnostics (800-394-4493), or as a service from Berlex Laboratories through IDX Labs.

As IFNb therapy will only provide a moderate reduction in the frequency and severity of relapses, the clinician must decide when "breakthrough" disease activity might indicate the development of neutralizing antibodies. Severe attacks in patients on the drug for a few years, especially those accompanied by gadolinium-enhancing activity on brain MRI, might be related to reduction in drug efficacy. If a patient had a persistently high antibody titer on two separate specimens drawn months apart, then alternative drug therapy might need to be considered. —Brian Apatoff