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19-09-2012 | Immunology | Article

Close monitoring could give early warning of MS disease course


Free abstract

medwireNews: Patients with multiple sclerosis (MS) who have breakthrough disease activity early in the course of treatment with interferon beta-1a (IFNβ-1a) are at high risk for severe worsening and poor long-term outcomes, research shows.

The risk associated with such breakthrough disease activity, especially new gadolinium-enhancing lesions on magnetic resonance imaging (MRI), was even higher than that associated with persistent disease activity among patients taking placebo, report Robert Bermel (Cleveland Clinic, Ohio, USA) and colleagues.

They say this finding "argues that there is value in monitoring for persistent active inflammation at treatment start and after initiating interferon." However, the researchers note that "there is no widely available methodology to quantify MRI lesion activity in a clinical setting."

The study involved 136 patients who participated in the pivotal MS Collaborative Research Group trial of IFNβ-1a. Treatment was at the discretion of doctors after the conclusion of the 2-year trial; at the time of the follow-up analysis, 15 years later, about half of all patients were taking IFNβ-1a.

The team's definition of severe worsening during follow up was an increase of at least 4.5 points on the Expanded Disability Status Scale Patients (the top quartile of change). Patients who were taking IFNβ-1a, yet developed two or more gadolinium-enhancing lesions over the course of a year in the original trial (23.9% of patients) were almost ninefold more likely to meet this endpoint, compared with those with one or no lesions.

The finding of two or more gadolinium-enhancing lesions was 55.5% sensitive and 87.7% specific for severe worsening of patients' condition. Although more patients in the placebo group had persistent disease activity by this measure (41.0%), it was less predictive of outcomes, at a sensitivity of 50.0% and a specificity of 64.1%.

Bermel et al suggest that breakthrough activity while on IFNβ-1a may identify patients with a biologically distinct subtype of MS with a severe phenotype.

"Early identification of that phenotype could be important in the current therapeutic environment, so that treatment with more highly effective therapy may be instituted earlier, in an attempt to avoid undesirable long-term outcome," they write in the Annals of Neurology. However, the researchers note that it is not clear which therapies should be used in patients who do not respond to IFN.

Other measures of breakthrough disease - new lesions on T2-weighted MRI and clinical relapses - were also associated with poor outcomes, although less significantly so than gadolinium-enhancing lesions.

They conclude: "The specific choice of treatment for patients with breakthrough disease on [intramuscular] IFN-β1a will be made through individualized discussions about the expected risks and benefits of currently available therapies."

medwireNews ( is an independent clinical news service provided by Springer Healthcare Limited. © Springer Healthcare Ltd; 2012

By Eleanor McDermid, Senior medwireNews Reporter

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