Wednesday, 14 March 2012

Research: Tysabri and PML



Background: Multifocal progressive leukoencephalopathy (PML) is associated with JC virus (JCV) seropositivity, past immunosuppression, and natalizumab treatment for two years or more. 


Aim: The aim of this study was to investigate the rate of treatment discontinuation after stratifying for the three risk factors in a group of 104 natalizumab-treated patients with relapsing-remitting multiple sclerosis. 


Methods: The investigators  investigated JCV serological status in their population. We then divided patients into groups according to their PML risk. Treatment indication was reassessed. Of the patients, 64 (61.5%) were JCV seropositive. Amongst seropositive patients on natalizumab for 2 years or more, 10 had received immunosuppression (group A), and 38 had not (group B). 



Results: After an informed and shared decision-making process, 6/10 (60%) from group A compared with 9/38 (23.7%) from group B discontinued treatment (p=0.027). In groups A and B, discontinuation also depended upon doctors' views (p=0.019, group A; p=0.010, group B) and clinical outcomes (p=0.021, group A). No-one from low-intermediate risk groups discontinued. 


Conclusions: The decision to discontinue natalizumab treatment is complex, even when clear PML risk rates are described. Clinical outcomes and doctors' idiosyncrasies play a crucial part in patients' final choice.


"The results are self-explanatory. What do you think?"

4 comments:

  1. For Pathway of Multiple Sclerosis http://rnspeak.com/pathophysiology/multiple-sclerosis-pathophysiology/#.T2BJbnl_42w

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  2. Is reducing the frequency of Tysabri infusions to every 6 weeks an option? If so, I would think people who are doing well on Tysabri would look into that rather than discontinuing use entirely. Is it possible those that decided to discontinue use were not seeing good results from Tysabri?

    I think it was this blog that posted an article about doing blood tests to determine the amount of Tysabri in the blood at a given time. Then customizing the infusion schedule to the patient. I think once those type of tests are calibrated they should eliminate the risk of PML entirely.

    Hopefully Biogen realizes that were such a test to be available and successful, demand for Tysabri would rise dramatically. It seems like compared to testing a new drug, developing that kind of procedure would be relatively cheap.

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  3. Re: "Then customizing the infusion schedule to the patient. I think once those type of tests are calibrated they should eliminate the risk of PML entirely."

    No this will not occur; for natallzumab to work it has to stop trafficking of white blood cells into the central nervous system. This is the risk factor for PML. I don't think there is a window that will allow some trafficking to prevent PML and still treat MS. The only way to prevent PML is to have treatment that eliminates the virus from the body. This is not some wild fantasy; it has been done with other viruses. For example new hepatitis C drugs eliminate the virus in the majority of sufferers.

    ReplyDelete
  4. Re: "Then customizing the infusion schedule to the patient. I think once those type of tests are calibrated they should eliminate the risk of PML entirely."

    No this will not occur; for natallzumab to work it has to stop trafficking of white blood cells into the central nervous system. This is the risk factor for PML. I don't think there is a window that will allow some trafficking to prevent PML and still treat MS. The only way to prevent PML is to have treatment that eliminates the virus from the body. This is not some wild fantasy; it has been done with other viruses. For example new hepatitis C drugs eliminate the virus in the majority of sufferers.

    ReplyDelete

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