Biomarker May Determine Disease Activity, Predict Next Relapse in MS

Megan Brooks

October 08, 2010

October 8, 2010 — Myxovirus resistance protein A (MxA) messenger RNA (mRNA) level in peripheral blood correlates with clinical and radiologic measures of disease activity in patients with newly diagnosed multiple sclerosis (MS), a new study shows.

"MxA mRNA has potential as a biomarker for clinical disease activity in MS," Laura F. van der Voort, MD, and colleagues from VU Medical Center, Amsterdam, the Netherlands, conclude in an article in the October 5 issue of Neurology.

In a prospective cohort of 116 therapy-naive patients diagnosed as having MS in the previous 6 months, the researchers measured baseline MxA mRNA levels and correlated them to clinical and magnetic resonance imaging (MRI) findings at baseline and during a median of 45 months.

They found that MxA mRNA (before therapy) was higher in the 93 patients who were clinically stable at baseline (in remission, no relapse or progression) than in the 23 having clinical exacerbations at baseline. Likewise, there were fewer MRI lesions in patients with a high MxA mRNA level relative to those with a low MxA mRNA level (mean, 0.9 vs 1.7).

A low MxA mRNA level was associated with the occurrence of relapse (P = .002) and contrast-enhancing lesions (CELs) on baseline MRI (P = .045). In addition, a high baseline MxA mRNA level correlated with a longer time to a first new relapse (hazard ratio [HR], 0.59; 95% confidence interval [CI], 0.35 – 1.00; P = .044).

Cumulative Value

According to the investigators, a high MxA level was as effective in predicting time to next relapse (HR, 0.59) as the absence of CELs (HR, 0.54). A combination of no CELs and high MxA mRNA level additively predicted lack of future disease activity (HR, 0.35; 95% CI, 0.17 – 0.74; P = .006), “clearly showing a cumulative value of combining both factors,” the researchers say.

On the basis of receiver-operator characteristic curve analysis, the optimal cutoff for MxA levels that discriminated between clinical remission and relapse at baseline was 0.0750. MxA levels below this cutoff were considered low; levels above this cutoff were considered high.

At enrollment, none of the patients had ever received disease-modifying treatment, but 55 (47%) started it during follow-up, most commonly an interferon-beta (IFN-β) preparation. Response to therapy was not predicted by baseline MxA mRNA levels in 40 patients treated during 2 of 4 years of follow-up for whom responder status could be determined.

But the author of a commentary in Neurology, Anthony T. Reder, MD, of University of Chicago, Illinois, cautions that the "group size, and the fact that data were pooled from 3 IFN-β preparations and glatiramer acetate, add to uncertainties about this negative conclusion."

The Big Picture

Studies have shown that MxA may be considered a surrogate marker of individual immunologic response to recombinant IFN-β in MS and a marker of average IFN levels in the circulation.

"The findings in the current study hint "that a person's innate/intrinsic 'set point' of IFN regulation and the proteins that IFN turns on will determine how that person will respond to IFN therapy,” Dr. Reder told Medscape Medical News. This is "important because MS patients are often abnormal in this regard even before any IFN therapy."

Dr. Reder believes "we are getting closer to personalizing neurology drugs, [learning] how to tailor the best therapy to every patient, and [we] hope to use a tailor with great skills for this."

Dr. van der Voort and coinvestigators and Dr. Reder disclose having received funding or serving on boards of various pharmaceutical companies. A complete list can be found in the original articles.

Neurology. 2010;75:1222-1223, 1228-1233.

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