Tuesday, 3 January 2012

Tysabri hangs around for a long time

Rispens T, Vennegoor A, Wolbink GJ, Polman CH, Killestein J. Natalizumab remains detectable in patients with multiple sclerosis long after treatment is stopped.Mult Scler. 2011 Dec 19. [Epub ahead of print]

Natalizumab is frequently used as a treatment for multiple sclerosis (MS). The occurrence of progressive multifocal leukoencephalopathy (PML) in natalizumab-treated patients indicates that its prominent beneficial effects need to be balanced against the risks. Also, cessation of the drug seems to be associated with recurrence of disease activity.

Both the moment of rebound disease activity and the outcome of PML are related to clearance of the drug. Specific features of this IgG4 antibody (i.e. half-antibody exchange) may result in underestimated drug levels. Here, we demonstrate natalizumab levels in 10 patients with relapsing MS, using a recently developed sensitive assay. Remarkably, natalizumab was detectable up to 200 days after cessation of therapy.

Although we will perhaps be shocked about how long the antibody hangs around, the important information about PML and rebound disease is not the length of time it takes for the antibody to disappear, but for how long is it functionally silencing the white blood cell response after stopping the drug

You may know that they can detect cannabinoids in your body for about a month after smoking cannabis but does it get you high for a month, of course not although I never inhaled if it did would Sativex have any chance?-Only joking but you see the point


13 comments:

  1. MouseDoctor,

    This is kind of random but I would like to know what are the differences between Fampridine and Nerispirdine? Both seem to be doing the exact same thing which begs the question, 'why do we need two different drugs that replicate each others benefits?'

    Why do pharmas invest time in creating facsimilies? Why not explore different drugs that achieve different positive results?

    Furthermore, Fampridine and Nerispridine are Aminopyridines, aren't they? Isn't there a school of thought that suggests Aminopyridines are dangerous to MS'ers?

    After all, your very own Prof G went on record to say: "Aminopyridines will almost certainly increase the energy requirements of damaged, vulnerable, demyelinated axons as they will require more energy for repolarization the process by which they get ready to transmit another electrical signal. There is now good evidence that increasing the energy requirements of axons may result in further axonal injury and loss."

    Should MS'ers eschew Fampridine on account of it potentially increasing disability in the long run?

    Happy New Year by the way.

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  2. Re: "This is kind of random but I would like to know what are the differences between Fampridine and Nerispirdine? Both seem to be doing the exact same thing which begs the question, 'why do we need two different drugs that replicate each others benefits?'"

    Pharma is a business and me too's make money. More often and not second or third in class drugs make more money than first in class drugs. This usually happens because they have a better safety or efficacy profile or sometime dosing regimen. The drug industry is no different to consumer goods; certain drugs to better than others. Often the latter is simply down to good branding and marketing.

    Developing a me too is less risky and costly than the development of a novel drug; the company that develops the novel drug shoulders a lot of the risk.

    What gets me down is the current cost of Fampridine! The current costing strategy is unsustainable.

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  3. Re "Isn't there a school of thought that suggests Aminopyridines are dangerous to MS'ers? After all, your very own Prof G went on record to say: 'Aminopyridines will almost certainly increase the energy requirements of damaged, vulnerable, demyelinated axons as they will require more energy for repolarization the process by which they get ready to transmit another electrical signal. There is now good evidence that increasing the energy requirements of axons may result in further axonal injury and loss.'"

    This is a theoretical risk and hasn't been shown to occur. Dr Mark Baker, an ion channel expert in our group, thinks the concentration of 4-aminopyrdine in the CNS of MS'ers will be too low to work directly on axonal conduction. In fact we don't really know how the drug is working; there is some data it is working at the level of the synapse.

    "Should MS'ers eschew Fampridine on account of it potentially increasing disability in the long run?"

    Not at present; we need data before making any such recommendation. Some MS'ers do very well on Fampridine and get a real improvement in their walking speed and ability that improves there quality of life. I don't want to deny them benefit based on a theoretical risk at this stage.

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  4. Prof G – I would like to get my consultant to put me on a course of Fampridine. I have PPMS and my problems are mainly to do with lower limb issues. I am tired of waiting for years in getting PCT to issue the drug. Is there any way I can get my consultant to apply directly to the PCT just for me rather than trying to get group approval? I really want to try Fampridine and find it unfair that others across the country have access to such treatments but others do not.

    Walking is the single biggest challenge I face. I would love to find a way to ease the struggle.

    BTW: what are your thoughts on the ‘assisted dying’ headlines in today’s news? I see that Debbie Purdy is doing the news outlet rounds giving her thumbs up to the cause. Don’t you think someone like Debbie Purdy, brilliant spokesperson she is, could serve the MS community better by championing the need for better and more efficacious treatments for PPMS’ers? I don’t deny she is suffering because of her MS, but I would love to see a more hopeful image of people with PPMS.

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  5. I think that if they ever come up with a way to cure PPMS, then Purdy should be one of the first to get treatment. That way she will hopefully realise how rotten it is to see someone with the same disease as me just going on every news channel to talk about how great it will be if we can have assisted suicide in Britain, when really her time would have been better served campaigning for better care and support for those with progressive MS.

    I was at my gym this morning and Purdy's beaming mug was all over Sky News, praising the'Right to Die' agenda. My heart sank and I suddenly felt disheartened seeing the image of Purdy talking about death. I have PPMS and work hard every day to keep going. I have been doing so for over six years now, even though my walking is highly problematic too. I'm active and want to see more hope from people with PPMS. Not the gloom. Being gloomy is too easy. Optimism is the key.

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  6. Re: "BTW: what are your thoughts on the ‘assisted dying’ headlines in today’s news?"

    As a doctor that cares for young people I am against assisted dying or suicide. This is not a religious stance. It is hard to be trying to make people better and improve their quality of life and to also offer assisted suicide as part of your care package. If it ever gets legalised I would leave it for others to do the job. I am also concerned about it being a slippery slope; where do you draw the line? On the other side of the coin it is inappropriate for the healthcare profession to prolong life unnecessarily. We all have to die at some time and it is better to die with dignity than to die in a way that is unpleasant or undignified. The problem with modern society is that we don't seem to embrace death in a way that our predecessors did. One of the traditional roles of a doctor was to help people in death. The current attitude amongst most doctors is to avoid or delay the issue of death for as long as possible. I think this is wrong.

    I would also not deny someone the right to choose the option of assisted suicide; for example I wrote a medical report for one my patients who wanted to register with dignitas, the clinic in Switzerland that offers assisted suicide. How could I say no? It was her and her husband's decision to explore this option, not mine. If I didn't write the report I would have been denying her right to choose. You may disagree with this, but then medicine is not a science, but an art. There is a lot of grey between the extreme positions of black and white.

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  7. Re: "Prof G – I would like to get my consultant to put me on a course of Fampridine. I have PPMS and my problems are mainly to do with lower limb issues. I am tired of waiting for years in getting PCT to issue the drug. Is there any way I can get my consultant to apply directly to the PCT just for me rather than trying to get group approval?"

    Yes. This is done via an IFR or individual funding request. It is quite a lot of work, but can be done if your neurologist is motivated and if your PCT has the money to spend. Unfortunately, we are seeing an increasing number of IFR's being turned down as the NHS budget freeze starts to bite.

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  8. Re: " BTW: what are your thoughts on the ‘assisted dying’ headlines in today’s news? .... PPMS’ers? I don’t deny she is suffering because of her MS, but I would love to see a more hopeful image of people with PPMS."

    Please see post above.

    I can't agree more about your stance on hope.

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  9. Prof G, I am confused on your opinion on assisted dying.

    You say you are not in favour of it but support the right for an individual to die with dignity.

    MS is a complex disease but it affects people in many different ways. The truth is that the disease does not get better, it just gets worse, but it can take years for it to seriously damage you. The option you have is to painfully and slowly get worse, or end your life whil you're still in reasonable condition. The big question is when is the right time for the individual to call it a day on their MS?

    Many people can opt for assisted dying right now, but when one considers what an active field MS research is, is this the best time to be contemplating suicide? Surely now is the time to try and keep going? Surely doctors should be telling patients about the hopeful possibilities regarding efficacious MS treatments on the horizon?

    I would like a more positive spin on MS news. CCSVI and asisted dying have clouded MS news for too long.

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  10. Re: "What gets me down is the current cost of Fampridine! The current costing strategy is unsustainable."

    What is the current cost? Why doesn't the NHS use its huge buying power to get the price knocked own?

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  11. Re: "What is the current cost?"

    ~£4,000 per year; this is expensive for a symptomatic therapy. In the US is costs ~$13,000 per year. Why should the US cost more? This is the problem with International drug pricing; it is unsustainable. The US market can't subsidise the rest of the world's medications.

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  13. Re: "Prof G, I am confused on your opinion on assisted dying. You say you are not in favour of it but support the right for an individual to die with dignity."

    Dying with dignity does not mean you have to have an assisted death.

    Dying with dignity is respecting each others wishes around dying. For example, for medics to accept that death is an inevitable consequence of being alive and not to try an prolong life at all costs.

    Advanced directives can help by providing guidance to doctors caring for people with chronic conditions. For example, you may not want to be admitted to hospital or an intensive care unit if you develop a serious chest infection; you may not want to be tube fed when you can't swallow anymore; you may prefer to die at home rather than in hospital. All these situations require some forethought and planning and in many cases a discussion with your families and loved ones. When I say that I am not personally in favour of assisted dying I mean I don't want to be part of the decision process or involved in the process in any way; other doctors can do it. I also won't judge anyone who chooses this option.

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