Natalizumab (Tysabri) is a disease-modifying drug currently given by intravenous infusion every 4 weeks and is commonly prescribed for the treatment of very active MS. It is quite effective at reducing relapse rates by around two-thirds and there is some evidence that it slows progression to disability. However, its use must be balanced against the risk of a rare but potentially deadly brain infection, progressive multifocal leukoencephalopathy (PML).
PML is thought to occur as a result of a mutation of the John Cunningham Virus (JCV), which is carried harmlessly in around half to three-quarters of the population. However, when the immune system is suppressed, as in the case of Tysabri, the virus can become uncontrolled and lead to PML. If diagnosed, there is around a 1 in 4 chance of death or serious disability.
As of January 2018, there have been 756 reported cases of PML, with a global incidence of 4.19 per 1,000 people treated with Tysabri. So this is a real problem.
If a patient with MS tests positive for JCV, they are usually either advised not to use the drug at all, or have treatment stopped after 2 years, when the risk of PML becomes too high. For those who test negative for JCV, the risk is much lower, at around 1 in 10,000.
When a person with MS stops Tysabri however, there is a risk of reactivation of their disease (immune reconstitution inflammatory syndrome – IRIS) to the same level as before starting the therapy. There is also a 1 in 10 chance of rebound in disease activity to a level worse than when they started.
This makes for very difficult discussions and decisions for neurologists and people with MS. They have to weigh up the positive effects of the drug in terms of relapse reduction and preventing disability, against the possibility of potentially deadly brain infection or worsening of their disease.
There is some recent positive news though. Researchers from NYU Langone Health recently presented a study at the Americas Committee for Treatment and Research in Multiple Sclerosis (ACTRIMS) Forum 2018 in San Diego. They showed that, if the interval between doses was extended to 5 – 12 weeks, over 6 years the risk of PML was reduced by nearly 100%.
Whilst their study didn’t assess whether the drug worked as well when the dosing was extended, previous research has shown that there was no negative impact on effectiveness when doses were 8 weeks apart, looking back at the records of 2,000 people.
The team are now planning to prospectively test extended dosing, with the aim that many more people with MS can remain on it in the longer term. This research is very reassuring for those taking or considering starting Tysabri, and certainly warrants detailed discussion with one’s neurologist.
Dr Jonathan White
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