Tysabri and the Rebound Effect

Stopping treatment may cause serious MS relapse in some

Tysabri is administered through an IV.
Tysabri is administered through an IV. Echo/Getty Images

Tysabri (natalizumab) is a disease-modifying drug used in treating relapse in persons with multiple sclerosis (MS). It impedes the ability of immune cells to cross the blood-brain barrier that separates the brain and spinal cord from the rest of the body. It is these cells that can cause damage to nerves as they inadvertently strip them of their protective coating (known as the myelin sheath).

Tysabri is approved by the U.S. Food and Drug Administration (FDA) for use in MS monotherapy (not to be combined with other therapies) and is administered intravenously every 28 days.

Risks Associated With Tysabri Use

While Tysabri has been shown to reduce relapse in people with MS by a striking 68 percent, it is not without its concerns. In 2005, the FDA issued a black box warning advising patients and doctors that Tysabri was around two of every 1,000 users experienced a potentially fatal brain infection known as progressive multifocal leukoencephalopathy (PML).

Another lesser known concern is the phenomenon known as rebound where discontinuation or interruption of the drug triggered a return of MS relapse symptoms, in some cases worse than when treatment was started.

Understanding the Rebound Effect

The Tysabri rebound effect was first identified in 2007 when Dutch investigators examined the MRI scans of people who had been taking Tysabri but had to stop when the drug was temporarily pulled from the market due to PML concerns.

During this 15-month treatment gap, the scientists found that the average number of lesions in the central nervous system had increased from an average of 3.43 at the start of treatment to 10.32 after treatment was stopped.

Strangely enough, this effect was not seen to worsen in persons who had been on treatment longer. In fact, it was just the opposite. According to the research, those who had undergone a couple of Tysabri treatments had five times more lesions than those who have been on the treatment for the entire duration of the study (roughly 36 infusions).

A similar study in 2014 supported these claims and concluded that the interruption of therapy was linked to a nearly two-fold increase in the risk of relapse. More concerning yet was the fact that a quarter of these individuals had more relapses after stopping Tysabri than before treatment was started.

What This Tells Us

Scientists do not entirely know why this rebound effect happens. The same has been noted in other MS drugs, including Gilenya (fingolimod), and there remains little insight as to what can be done to prevent it.

What we do know is this: the persons at greatest risk are those who only take a couple of months of Tysabri and then stop. If treatment with Tysabri is recommended, you as the patient need to commit to treatment and stick with it. You cannot take arbitrary drug holidays or decide to stop if and when you are feeling better.

Treatment ultimately needs to be directed by a qualified specialist who can better determine if and when Tysabri is no longer needed.

Sources:

Fox, R.; Cree, et al. "MS disease activity in RESTORE: a randomized 24-week natalizumab treatment interruption study." Neurology 2014; 82(17):1491-8.

Sorensen, P.; Koch-Henrikson, H.; Petersen, T. et al. "Recurrence or rebound of clinical relapses after discontinuation of natalizumab therapy in highly active MS patients." J Neurol. 2014; 261(6):1170-7.

Vellinga, M.; Castelijns, J.; Barkhof, F. et al. "Postwithdrawal rebound increase in T2 lesional activity in natalizumab-treated MS patients." Neurology. 2008; 70(13):1150-1.

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