Brain volume-protecting DMTs may slow MS disability progression

Disease-modifying therapies (DMTs) can significantly slow the loss of brain volume in adults living with multiple sclerosis, and this slowing links closely to better long-term physical outcomes, according to a new large review of clinical trials.

The findings suggest that treatments which best protect brain tissue also help delay disability over time. This strengthens the case for using changes in brain volume as an important way of measuring how well treatments work in multiple sclerosis.

Researchers from Switzerland and Italy carried out a network meta analysis, a method that allows different treatments to be compared even when they have not been tested directly against each other. They combined data from 33 randomised controlled trials involving 26,247 adults living with multiple sclerosis. All studies followed participants for at least one year and included treatments already approved for use.

Across a median follow-up period of two years, eight of the 16 DMTs studied significantly reduced brain volume loss when compared with a placebo. The strongest effect was seen with ponesimod, which reduced brain volume loss by 48 percent. Other therapies linked with a meaningful reduction included ofatumumab, alemtuzumab, teriflunomide, ozanimod, natalizumab, siponimod, and fingolimod.

All 16 therapies reduced signs of disease activity on MRI scans, and six were also shown to delay confirmed disability progression. Notably, four of the eight treatments that slowed brain volume loss also reduced disability progression. Ofatumumab showed the strongest effect in this area, cutting disability accumulation by 52 percent.

The researchers found a clear link between how well a treatment preserved brain volume and how effectively it slowed disability progression. This association remained even after accounting for visible lesions on MRI scans, suggesting that protecting brain tissue may offer benefits beyond reducing inflammation alone.

While the studies varied in scan methods, definitions, duration, and whether people had used treatments before, the overall message was consistent. Several disease-modifying therapies substantially reduce brain volume loss in multiple sclerosis, and this reduction links to better long-term physical outcomes.

The researchers concluded that measuring brain volume loss should play an important role in future clinical trials that aim to reduce long-term disability in people living with multiple sclerosis.