DMTs that protect brain volume may also slow disability progression
Analysis shows clear link between brain atrophy and MS symptom progression
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- Disease-modifying therapies (DMTs) significantly slow brain volume loss in multiple sclerosis patients.
- Reduced brain volume loss directly correlates with decreased long-term disability progression in MS.
- DMTs like Ponvory and Kesimpta are effective, highlighting brain volume as a key treatment target.
Specific disease-modifying therapies (DMTs) significantly slow the rate of brain volume loss in adults with multiple sclerosis (MS), a benefit that is directly linked to reduced long-term disability, according to a new review.
A network meta-analysis of more than 26,000 patients confirms that therapies most effective at preserving brain tissue are also those that can best delay physical decline, thereby strengthening the case for using brain volume as a key measure of treatment efficacy.
“These results strengthen the role of BVL [brain volume loss] as a clinically relevant biomarker and a meaningful therapeutic target in MS management,” researchers wrote.
The meta-analysis, “The effect of disease-modifying therapies on brain volume loss and disability accumulation in multiple sclerosis: a systematic review and network meta-analysis,” was published in The Lancet Regional Health – Europe.
Brain volume loss and disability
MS occurs when the immune system mistakenly attacks myelin, the fatty substance that protects nerve cells in the brain and spinal cord. These immune attacks damage both myelin and nerve cells, resulting in lasting symptoms that can lead to disability.
In people with MS, increased brain atrophy — a reduction of overall brain volume caused by a loss of nerve cells and their connections — is correlated with a greater degree of disability. Thus, tracking brain volume loss may be used to predict long-term disability.
Although several DMTs have been shown to slow brain atrophy in MS, it is still difficult to compare their effects because few studies have tested them directly against each other. Additionally, it is unclear to what extent a reduction in brain atrophy correlates with improvements in disability progression trajectories.
To address this, researchers in Switzerland and Italy conducted a network meta-analysis. This type of analysis allows both direct and indirect comparisons between therapies, even if they were not tested head-to-head, by combining data from a network of studies.
Their meta-analysis included 33 randomized controlled trials involving 26,247 adults with MS. Studies had to report brain volume loss over at least one year and include DMTs approved in the U.S.
Over a median follow-up of two years, eight of the 16 DMTs that were assessed significantly reduced brain volume loss compared with a placebo. These included Ponvory (ponesimod) — which showed the strongest effect, with a 48% reduction — Kesimpta (ofatumumab), Lemtrada (alemtuzumab), Aubagio (teriflunomide), Zeposia (ozanimod), Tysabri (natalizumab), Mayzent (siponimod), and Gilenya (fingolimod).
All 16 DMTs reduced MRI activity, and six also delayed confirmed disability progression. Notably, four of the eight drugs that reduced brain atrophy were also found to slow disability progression. Kesimpta showed the strongest effect, reducing disability accumulation by 52%.
Consistently, a therapy’s effect on brain atrophy was significantly associated with its impact on disability progression, the researchers found. This link remained significant after accounting for lesions, suggesting that preserving brain volume has benefits beyond reducing visible inflammation on MRI scans.
Despite differences in how MRI scans were obtained, how parameters were defined, how long the studies lasted, and whether patients had received any prior therapies, “several DMTs substantially reduce BVL in MS, with this being linked to reduced disability progression,” the researchers wrote.
“These findings collectively highlight the importance of assessing BVL in trials targeting long-term disability accrual,” they concluded.
