Wednesday, 9 November 2011

Research: Steroids are not the answer for a Tysabri holiday

Borriello et al. Pulse monthly steroids during an elective interruption of natalizumab: a post-marketing study. Eur J Neurol. 2011 Nov 7. doi: 10.1111/j.1468-1331.2011.03577.x. [Epub]

Background and purpose:  Temporary discontinuation of natalizumab/Tysabri is sometimes considered because of the observed risk of progressive multifocal leukoencephalopathy (PML) in patients with multiple sclerosis (MS). However, interruption of natalizumab may result in a re-start of disease activity.


Methods:  In this prospective post-marketing study, 23 patients with MS treated with natalizumab elected a trial of treatment interruption (90-150 days) because of safety concerns on the risk of developing PML. To reduce the risk of disease activity return, patients received monthly intravenous (i.v.) steroid pulses before natalizumab re-start.


Figure - mode of action: Natalizumab works by coating white blood cells and preventing them from entering the brain and spinal cord. By doing this it prevents relapses, but also put treated subjects at risk of infection; we need white blood cells to traffic through the nervous system to clear infections. 

Results:  Despite the steroid coverage, seven patients (30.4%) had an active scan during the natalizumab interruption period; of these, four also had a concomitant clinical exacerbation.

Conclusions:  Our findings suggest that i.v. steroids are not currently recommendable as drug coverage during a scheduled treatment interruption period.

"The conclusions say it all, we need to find an alternative"

6 comments:

  1. How do T-cells breach the blood-barrier in the first place?

    "we need white blood cells to traffic through the nervous system to clear infections"

    I thought T-cells and other lymphocytes had to be kept out of the CNS via the blood-brain barrier and a breach in the barrier can lead to MS?

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  2. Re: "I thought T-cells and other lymphocytes had to be kept out of the CNS via the blood-brain barrier and a breach in the barrier can lead to MS?"

    No this is not entirely correct. The blood-brain-barrier is only a relative barrier and allows cells to migrate through it all the time. These cells survey the central nervous system to look for infections and tumours. If we block these cells from getting in we put ourselves at risk of not being able to fight off an infection if one occurs; this is what happens when MS'ers develop PML as a complication of natalizumab (Tysabri) treatment. I am not sure that a breach in the barrier causes MS, rather MS results in the barrier being leaky. Inflammation opens the barrier.

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  3. What kind of steroids did they use? Cortisone?

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  4. After the intended two year period for NAtalizumab in patients with MS, which is now a days the best treatment option?

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    1. Re: "After the intended two year period for NAtalizumab in patients with MS, which is now a days the best treatment option?"

      It depends on local availability and individualised care. Most of our MSers are choosing to go onto a high-efficacy drug as they have previously failed 1st-line injectables, i.e. fingolimod. In the near future we hope to have DMF and Alemtuzumab as well as choices. I have concerns about using Alemtuzumab post-natalizumab in high-risk PML cases as the treatment is irreversible.

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