Sunday, 22 December 2013

Accepting the risk of natalizumab treatment

What risk are you prepared to take with your MS? #MSBlog #MSResearch

"The study below confirms my clinical observations that risk perception is affected by many factors and differs form one MSer to the next, and over time. MSers with early relatively inactive disease have a different PML risk threshold than those with highly-active or rapidly-evolving severe MS. The latter is understandable; if you have very active disease and are now doing well on natalizumab with no relapses and little disability would you want to take the risk of rebound on withdrawal, or move to a potentially less effective therapy? Your experience of having bad MS that is now under control is your counterbalance of the risk of possibly developing PM in the future. I also have several MSers under my care who are so risk adverse that they would rather take their chances with MS; it may be a coincidence but this latter group of  MSers are often religious. In other words The course of their life is predetermined and whatever modern medicine has to offer this will not change their destiny."

"Despite MSers early in their course of disease - who typically have inactive disease and no disability - being generally relatively risk adverse there is a significant minority of MSers who soon after diagnosis are prepared to take huge risks to treat, and hopefully suppress or cure, their disease. These MSers tend to self-aware individuals who have done a lot of research about MS via the web and are acutely aware of the prognosis of MS if left to its own devices. These are the MSers who want to be treated with alemtuzumab or bone marrow transplantation as soon as possible. I find it difficult talking these people out of this situation, which I am forced to do, knowing full well that if I had been diagnosed with MS I would want to go this route. The reality in the UK is that early induction therapies are simply not available under the NHS to treat MS. Maybe NICE will recapitulate and allow us to use alemtuzumab and more importantly to use it first-line?"  

"Risk is a large subject and needs more time; when I get a moment in the future I will post something from the psychology literature on this topic. It is very interesting in that personality and gender play a role in risk perception. What I do know is that in general neurologists are more risk adverse than MSers and this may be half the problem we are having in getting the field to move toward early highly-effective treatments and the paradigm of treating-2-target of NEDA."

Tur et al. Risk acceptance in multiple sclerosis patients on natalizumab treatment. PLoS One. 2013 Dec 10;8(12):e82796. doi: 10.1371/journal.pone.0082796.

OBJECTIVE: We aimed to investigate the ability of natalizumab (NTZ)-treated MSers to assume treatment-associated risks and the factors involved in such risk acceptance.

METHODS: From a total of 185 MSers, 114 MSers on NTZ as of July 2011 carried out a comprehensive survey. We obtained disease severity perception scores, personality traits' scores, and risk-acceptance scores (RAS) so that higher RAS indicated higher risk acceptance. We recorded JC virus status (JCV+/-), prior immunosuppression, NTZ treatment duration, and clinical characteristics. NTZ MSers were split into subgroups (A-E), depending on their individual PML risk. Some 22 MSers on first-line drugs (DMD) acted as controls.

RESULTS: No differences between treatment groups were observed in disease severity perception and personality traits. RAS were higher in NTZ than in DMD patients (p<0.01). Perception of the own disease as a more severe condition tended to predict higher RAS (p=0.07). Higher neuroticism scores predicted higher RAS in the NTZ group as a whole (p=0.04), and in high PML-risk subgroups (A-B) (p=0.02). In low PML-risk subgroups (C-E), higher RAS were associated with a JCV+ status (p=0.01). Neither disability scores nor pre-treatment relapse rate predicted RAS in either group.

CONCLUSIONS: Risk acceptance is a multifactorial phenomenon, which might be partly explained by an adaptive process, in light of the higher risk acceptance amongst NTZ-treated MSers and, especially, amongst those who are JCV seropositive but still have low PML risk, but which seems also intimately related to personality traits.

Conflicts: multiple


  1. Prof G,

    Thanks for this post. You are right, very different attitudes to risk exist. My view was that I only get one life so happy to take high risks if it provides a chance of keeping well for as long as possible. I know someone with MS who is wheelchair bound, but want to show everyone that she deals with this is a positive way. She had no interest in treatments. I suppose we are all different.

    Any thoughts on what we might see in 2014? I'm talking in general terms. Will any neuroprotective trial results be announced? Any more news expected on anti-lingo?

    I think you once set out Team G's research priorities on year. Would be interested to hear what they are now.

    Thanks to you and Mouse for all the work,on the blog. Gives a lot of us hope.

  2. Prof G,

    I saw this on another website - claims PML cases are much higher. thoughts?

    "I compiled this information on PML reporting, because I wanted to understand how adverse effects were tabulated. Here is what I learned.

    Biogen is not required by the FDA to keep tabulation or a compilation of all deaths or side effects due to Tysbri--they are only required to record adverse effects directly reported to them by doctors, utilizing a particular protocol.

    This is why they are being sued by patients who now have PML, who believe they were not told of the true risk. ... story.html

    The FDA has a self-reporting system for patients and physicians to report adverse affects to drugs. It is called the FDA Adverse Event Reporting System. It is not for consumer use, and therefore, it is not possible to search for specific drugs (like Tysabri) and find out adverse events. IT IS NOT A USER FRIENDLY SYSTEM. You cannot just seach "Tysabri" and get get a 25 MB file, and have to go thru it with a fine tooth comb. And right now, the records only go thru 2012.
    That means that adverse effects for 2013 are not even included yet. ... 082193.htm

    What does this mean? We have no clue how many cases of PML exist right now.
    The EHealthMe site is very important, because it keeps track, in real time, of reported adverse effects, and is updated regularly by patients, doctors and the FDA.

    Hope this explains why the numbers are so different, depending on the source."

  3. Knowing that patients are less risk adverse than neurologists may help explain the appeal of CCSVI jugular angioplasty as well, with its known risks and unknown benefits.

  4. From my experience, sadly most in the medical profession are paternalistic.

    I am a well educated individual with well thought-out moral and ethical positions, plus an intensively discussed attitude to life (heart beat) as opposed to living. Why should medical professionals tell me what they're willing to risk when it is my life and living that is at risk? Death holds no fears for me: disability does. I am JCV negative and taking Tysabri - I wanted to be prescribed it even if I'd been JCV positive, but my neuro would not have prescribed it had I been positive. It is my life (and death), not his, so this made me incredibly angry.

    I appreciate that euthanasia and associated treatment / withholding of treatment is a very emotive subject, but it is offensive to be treated as an idiot who doesn't understand the risks.


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