Comparing treatment options after stopping natalizumab

31 August 2023

  • Long-term use of natalizumab (Tysabri®) is of concern due to an increased risk of a brain infection caused by JC virus.
  • Ceasing natalizumab treatment is associated with a high risk of rebound disease activity, so it is important people are switched to an alternative disease modifying therapy (DMT).
  • Researchers from the MSBase Study Group have compared the effectiveness of three DMTs commonly used after discontinuation of natalizumab.

How does natalizumab work?

Natalizumab (Tysabri®) is a monoclonal antibody that locks onto white blood cells, preventing their movement into the brain and spinal cord to attack the myelin or nerves.

Long-term use of natalizumab is associated with an increased risk of progressive multifocal leukoencephalopathy (PML), a serious brain infection caused by JC virus (JCV).

People living with MS treated with natalizumab who become positive for anti-JCV antibody generally discontinue treatment to mitigate the risk of PML.

They are typically switched to an alternative treatment due to the high relapse risk after stopping natalizumab.

In particular, the risk of rebound disease activity is high around 12 weeks after cessation of natalizumab when residual medication effects appear to be lost.

Common disease modifying therapies (DMTs) used after cessation of natalizumab include fingolimod (Gilenya®), dimethyl fumarate and ocrelizumab (Ocrevus®).

However, evidence has been inconsistent regarding the comparative effectiveness of these three DMTs after switching from natalizumab.

What did the researchers do?

Published in JAMA Neurology and led by Professor Helmet Butzkueven as part of the MSBase Study Group, the researchers conducted a study using information collected from MSBase, a large international clinical database, to compare the outcomes of people treated with fingolimod, dimethyl fumarate and ocrelizumab after natalizumab discontinuation.

The researchers focused on people who had taken natalizumab for at least six months.

What did the researchers find?

The researchers focused on 1,386 people with relapsing remitting MS who met the selection criteria.

Of these, 823 people were treated with fingolimod, 138 people were treated with dimethyl fumarate, and 425 people were treated with ocrelizumab.

Treatment with ocrelizumab was associated with a significant reduction in the average number of relapses over the course of a year (annualised relapse rate) compared to fingolimod and dimethyl fumarate.

People treated with fingolimod or dimethyl fumarate after stopping natalizumab had a significantly higher risk of experiencing their first relapse than those taking ocrelizumab.

There were no significant differences in annualised relapse rate and time to first relapse between fingolimod and dimethyl fumarate.

Next, the researchers focused on disability progression. As there were only a small number of people taking dimethyl fumarate who met the confirmed disability progression criteria, the researchers only compared those people treated with fingolimod and ocrelizumab.

Fingolimod was associated with a higher risk of disability accumulation compared to ocrelizumab.

Compared with ocrelizumab, people taking fingolimod and dimethyl fumarate were more likely to discontinue treatment, and compared with dimethyl fumarate, people taking fingolimod were less likely to discontinue treatment.

What does this mean?

These findings indicate that, among people living with MS who had discontinued natalizumab treatment, ocrelizumab was associated with a significant reduction in annualised relapse rate, an increase in time to first relapse, and a lower discontinuation rate compared to fingolimod and dimethyl fumarate.

These findings will hopefully inform choices for people who need to discontinue natalizumab treatment.

It is important to note that the results of this study are only applicable to natalizumab treatment switches due to the rapid loss of its biological effects once ceased. They cannot be generalised for switches from other treatments.

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Comparing treatment options after stopping natalizumab