Slowing progression

In short

Disability can keep worsening even when relapses have stopped. This is called progression, and it is the main cause of long-term disability.

Most medicines that stop relapses do little against it, so it is the biggest unmet need in MS.

The leading explanations are inflammation trapped inside the brain, nerve fibres running short of energy and repair that fails with age. Only a few medicines have slowed progression in trials.

Where we are

• Progression without relapses drives most long-term disability, and the medicines that stop relapses slow it only partly.
• Tolebrutinib is the first medicine confirmed to slow disability in non-relapsing secondary progressive MS (HERCULES, 2025). The EU approved it in 2026 and the FDA did not.
• Ocrelizumab remains the only medicine approved for primary progressive MS, with a modest effect.
• The mechanisms under test are smouldering inflammation behind the blood-brain barrier (BTK inhibitors, microglia), failing energy supply in nerve fibres, and blood vessel factors.

Written by the editors from the records below. Last reviewed 6 November 2026. Not yet reviewed by an MS specialist.

The evidence

What comes next

Further reading

References

The sources behind this area's background are listed with its Research background in MS in depth. Every trial, hypothesis, review and lab study above links to its own record.