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Updated: May 28, 2026
Magnetic Resonance Imaging of Multiple Sclerosis at 7.0 Tesla
Published on: February 19, 2021
Combined MRI lesions and relapses as a surrogate for disability in multiple sclerosis
M P Sormani1, D K Li, P Bruzzi
1Biostatistics Unit, Department of Health Sciences, University of Genoa, Genoa, Italy. mariapia.sormani@unige.it
Objective:
In multiple sclerosis (MS), the aim of therapies is to prevent the accumulation of irreversible disability. This is difficult to assess given the short time course of clinical trials. MRI markers and relapses are often used as surrogate of disability in MS studies, but their validity remains controversial. We sought to validate, at the individual patient level, MRI lesions and relapses as surrogates for disability progression over the course of MS trials.
Methods:
Individual patient data from a large, placebo-controlled trial of interferon β-1a in relapsing-remitting MS (RRMS) were analyzed. The Prentice criteria were applied to evaluate surrogacy of 1-year MRI active lesions and relapses for disability worsening (Expanded Disability Status Scale [EDSS]) over the 2-year follow-up.
Results:
All Prentice criteria were satisfied. Treatment reduced by 31% the odds of having EDSS worsening over 2 years, reducing the mean number of MRI lesions by 61% and the mean number of relapses by 36% over 1 year. Both 1-year MRI lesion activity and relapses, when considered independently, accounted for more than 60% of the treatment effect on 2-year EDSS worsening. A combination of 1-year MRI lesion activity and relapses explained 100% of the treatment effect on EDSS worsening over 2 years.
Conclusions:
A combined measure of 1-year changes in MRI lesions and relapses after interferon therapy fully estimated the corresponding effect on 2-year EDSS worsening. This short-term combined measure appears to be a surrogate for disability progression over a longer term when evaluating the effect of interferon in RRMS.
Insights
In multiple sclerosis, MRI lesions and relapses measured over one year effectively predict long-term disability worsening after interferon therapy, validating their use in clinical trials.
Area of Science:
- Neuroscience
- Clinical Neurology
- Medical Imaging
Background:
- Therapies for multiple sclerosis (MS) aim to prevent irreversible disability, a difficult endpoint to assess in short clinical trials.
- MRI lesions and relapses are commonly used as surrogate markers for disability in MS studies, but their validity is debated.
- Validating these surrogates at the individual patient level is crucial for assessing treatment efficacy in MS.
Purpose of the Study:
- To validate MRI lesions and relapses as surrogates for disability progression in multiple sclerosis (MS) at the individual patient level.
- To assess the utility of short-term MRI and relapse data in predicting long-term disability outcomes in MS clinical trials.
- To determine if a combined measure of MRI activity and relapses can serve as a reliable surrogate for disability worsening.
Main Methods:
- Analysis of individual patient data from a large, placebo-controlled trial of interferon β-1a in relapsing-remitting MS (RRMS).
- Application of the Prentice criteria to evaluate the surrogacy of 1-year MRI active lesions and relapses for disability worsening (Expanded Disability Status Scale [EDSS]).
- Assessment of disability worsening over a 2-year follow-up period.
Main Results:
- Interferon therapy reduced the odds of EDSS worsening by 31% over 2 years.
- One-year MRI lesion activity decreased by 61% and relapses by 36% with treatment.
- Independently, 1-year MRI lesion activity and relapses each accounted for over 60% of the treatment effect on 2-year EDSS worsening.
- A combined measure of 1-year MRI lesion activity and relapses explained 100% of the treatment effect on 2-year EDSS worsening.
Conclusions:
- A combined measure of 1-year changes in MRI lesions and relapses after interferon therapy fully estimated the treatment effect on 2-year EDSS worsening.
- This short-term combined measure serves as a valid surrogate for longer-term disability progression in evaluating interferon's effect in RRMS.
- The findings support the use of combined MRI and relapse data as reliable short-term endpoints in MS clinical trials.
