Zero tolerance for disease activity on treatment is near (but not yet)


REPORT FROM THE EUROPEAN CHARCOT FOUNDATION ANNUAL MEETING – BAVENO, ITALY, NOVEMBER 28-30, 2013 – Recent studies have attempted to identify baseline disease characteristics that would predict response to a given treatment, but no factors have been determined thus far. However, markers of disease activity during treatment can be useful for identifying treatment failure.

A long-term cohort study of 283 RRMS patients examined response parameters in the first two years of treatment that were predictive of a worse outcome at 12 years. Worse outcome was defined as SPMS, EDSS 6, or a minimum 5-point increase in EDSS at 12 years (Tintoré M. ECF 2013). Tintoré et al. found that one clinical relapse, EDSS change or a combination of the two during the first 24 months of therapy was predictive of a poorer outcome. These results were similar to a recently published 15-year follow-up study, which reported that persistent disease activity (relapses, new T2 lesions or Gd-enhancing lesions) in the first two years on interferon-beta treatment was predictive of severe EDSS worsening (Bermel et al. Ann Neurol 2013;73:95-103).

MRI activity on treatment has also been shown to be predictive of disability. A meta-analysis of 13 trials (n=13,500) reported that the impact of treatment on active MRI lesions number and brain atrophy explained 75% of the effect of treatment on disability progression (Sormani et al. Ann Neurol 2013; epublished September 5, 2013). The MAGNIMS study group also found that central atrophy and lesion volume change predicted EDSS at 10-year follow-up (Popescu et al. Ann Neurol J Neurol Neurosurg Psychiatry 2013;84:1082-1091).

Combining endpoints to calculate a Rio score or modified Rio score has been shown to be useful in determining an individual patient’s response to treatment (Río et al. Ann Neurol 2006;59:344-352; Sormani et al. Mult Scler 2013;19:605612). For patients with intermediate scores suggestive of a suboptimal response, a repeat MRI at 18 months can clarify whether the patient is responding or is a candidate for an alternative therapy.

Dr. Tintoré concluded that the day is approaching when treatment success will be defined as zero tolerance for disease activity (relapses, EDSS progression, new MRI lesions). However, this criterion may be too rigorous and will need to be properly evaluated in clinical studies.

Reviewer: Dr. Daniel Selchen. Head of Neurology, St. Michael’s Hospital, Toronto, Canada.

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