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Updated: Jul 2, 2026
Comprehensive Autopsy Program for Individuals with Multiple Sclerosis
Published on: July 19, 2019
Impact of multiple sclerosis disease-modifying therapies on chronic lesion tissue expansion
Daniel Guilfoyle1, Kayla Ward1, Samuel Klistorner2
1Brain and Mind Centre, The University of Sydney, Sydney, NSW, Australia; Royal Prince Alfred Hospital, Sydney, NSW, Australia.
Background:
Chronic lesion tissue expansion (CLTE) reflects slow, concentric growth of established multiple sclerosis (MS) lesions and is linked to central brain atrophy and disability progression. Whether existing MS disease-modifying therapies (DMTs) differentially influence this aspect of progressive MS biology remains unclear.
Objectives:
To compare the effect of current DMTs on CLTE in a multicentre, real-world MS cohort.
Methods:
We conducted a retrospective, observational study using linked clinical data from MSBase and the MSBase Imaging Repository. Data from patients aged ⩾18 years with ⩾3 longitudinal MRI scans, and 7 therapies with ⩾100 stable treatment epochs were included. Therapy effects on CLTE, new T2 lesions, and brain atrophy were assessed using epoch-based covariate-adjusted generalised estimating equation models, with fingolimod as a comparator.
Result:
The cohort included 564 patients contributing 1648 stable treatment epochs. After adjustment for demographic, clinical, and imaging covariates, B-cell depleting therapy was the only DMT associated with significantly lower CLTE (β = -4.03, p = 0.017) relative to fingolimod. CLTE was independently associated with age, baseline lesion volume, and centre effects.
Conclusions:
B-cell depletion is associated with reduced CLTE, a promising biomarker of progressive MS biology.
Insights
B-cell depleting therapies significantly reduced chronic lesion tissue expansion (CLTE) in multiple sclerosis (MS) patients compared to fingolimod. This finding highlights B-cell depletion as a potential therapeutic strategy for progressive MS.
Area of Science:
- Neuroimmunology
- Clinical Neurology
- Radiology
Background:
- Chronic lesion tissue expansion (CLTE) is a key feature of progressive multiple sclerosis (MS), correlating with brain atrophy and disability.
- The impact of current disease-modifying therapies (DMTs) on CLTE remains incompletely understood.
Purpose of the Study:
- To evaluate and compare the effects of various DMTs on CLTE in a real-world, multicenter MS cohort.
- To identify which DMTs may influence the progression of MS lesions.
Main Methods:
- Retrospective observational study utilizing linked clinical and MRI data from the MSBase registry.
- Inclusion criteria: patients ≥18 years, ≥3 MRI scans, and ≥100 stable treatment epochs across 7 therapies.
- Generalized estimating equation models were used to assess therapy effects on CLTE, adjusting for covariates, with fingolimod as the reference treatment.
Main Results:
- Analysis included 564 patients and 1648 treatment epochs.
- B-cell depleting therapy was the only treatment significantly associated with reduced CLTE compared to fingolimod (β = -4.03, p = 0.017).
- CLTE was independently associated with patient age, baseline lesion volume, and study center.
Conclusions:
- B-cell depletion demonstrates a significant association with reduced CLTE in MS.
- This suggests B-cell depleting therapies may represent a promising approach to target progressive MS biology and its associated lesion expansion.
