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Determinants of long-term paramagnetic rim lesion evolution in people with multiple sclerosis
Jack A Reeves1, Alexander Bartnik1, Maryam Mohebbi1
1Buffalo Neuroimaging Analysis Center, Department of Neurology, Jacobs School of Medicine and Biomedical Sciences, University at Buffalo, State University of New York, Buffalo, New York, USA.
Objective:
Baseline paramagnetic rim lesion (PRL) load predicts disease progression in people with multiple sclerosis (pwMS). Understanding how PRLs relate to other known MS-related factors, and the practical utility of PRLs in clinical trials, is crucial for informing clinical decision-making and guiding development of novel disease-modifying treatments (DMTs).
Methods:
This study included 152 pwMS enrolled in a larger prospective, longitudinal cohort study who had 3T MRI scans and clinical assessments at baseline and 5- or 10-year follow-ups. PRLs were identified on baseline 3T quantitative susceptibility maps and classified as persisting, disappearing, or newly appearing at follow-up. The relationships between PRL evolution and clinical, radiological, environmental, and genetic characteristics were assessed, and clinical trial sample sizes were estimated using PRL appearance or disappearance as outcome measures.
Results:
DMT use was associated with lower odds of new PRL appearance (for high-efficacy DMTs: odds ratio = 0.088, p = 0.024), but not disappearance. Current smoking status was associated with greater baseline PRL number (B = 0.527 additional PRLs, p = 0.013). A 24-month clinical trial in people with progressive MS for a DMT that doubles the rate of PRL rim disappearance would require an estimated 118 people with progressive MS per group at 80% statistical power.
Interpretation:
Early MS diagnosis and subsequent DMT initiation may reduce new chronic active inflammation. However, the utility of PRL disappearance or new PRL appearance as outcome measures in clinical trials is limited by potentially large sample sizes that are needed for moderate efficacy drugs.
Insights
Paramagnetic rim lesions (PRLs) in multiple sclerosis (MS) are linked to disease progression. While high-efficacy treatments may reduce new PRLs, their appearance or disappearance requires large clinical trial sample sizes.
Area of Science:
- Neuroimmunology
- Radiology
- Clinical Trials
Background:
- Paramagnetic rim lesions (PRLs) are key indicators of active inflammation in multiple sclerosis (MS).
- Understanding factors influencing PRLs and their utility in clinical trials is vital for advancing MS treatment.
- Baseline PRL load predicts disease progression in people with MS (pwMS).
Purpose of the Study:
- To investigate the relationship between PRL evolution and various MS-related factors.
- To assess the practical utility of PRLs as outcome measures in clinical trials for novel disease-modifying treatments (DMTs).
Main Methods:
- Analysis of 3T MRI scans and clinical data from 152 pwMS over 5-10 year follow-ups.
- Identification and classification of PRLs (persisting, disappearing, new) on quantitative susceptibility maps.
- Assessment of associations between PRL changes and clinical, radiological, environmental, and genetic factors; estimation of clinical trial sample sizes.
Main Results:
- High-efficacy DMT use correlated with reduced new PRL appearance (OR=0.088, p=0.024).
- Current smoking was linked to a higher baseline PRL count (B=0.527, p=0.013).
- A 24-month clinical trial for a DMT doubling PRL rim disappearance rate would need ~118 pwMS per group.
Conclusions:
- Early MS diagnosis and DMT initiation may decrease new chronic active inflammation.
- PRL appearance or disappearance may have limited utility as clinical trial outcomes due to substantial sample size requirements for drugs with moderate efficacy.
