Sunday, 5 January 2014

Clinic Speak: What is a high PML risk?

What is your risk of developing PML on natalizumab? #ClinicSpeak, #MSBlog, #MSResearch

"What is a high risk of developing PML for MSers on natalizumab? Like beauty is in the eye of the beholder, risk-taking, and risk-aversion, is a personal decision that needs to be taken by an individual in consultation with their neurologist. What we do know from research is that on average neurologists are more risk-adverse than MSers. In addition, risk perception depends on a lot of factors, most of which are personal to you, and how the data is presented."

"We have developed the following aid to try and simplify the presentation of the information. You can download it by clicking on the Slideshare link on the bottom left of the embedded document. Please let us know if there is anything you don't understand on the infographic. It would also help us if you let us know how helpful you found it. Thanks."





CoI: multiple

18 comments:

  1. Thanks for this.
    Regarding the risk-averse/taker eye of the beholder aspect:
    Are you able to provide some examples of well known things that have comparable ratios of occurring (or maybe not occurring), say 1:100, 1:1000 and 1:10,000?
    For example, I once was told that taking the oral contraceptve comes with a 1:1000 chance of still becoming pregnant. Don't know if it is true but if so it seems a risk people who don't want to become parents are commonly prepared to take.
    Or not necessarily meds, what's the chance of being in a car accident by age 35 or snow on Christmas Day in London??
    Not that it is comparable but it gives some context as to what sort of 'risks' we go around ignoring or seeking to avoid - does that make sense?

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    1. Before MS i worked in pensions, running schemes and advising employers,one of my 'favourite' areas of work was calculating scheme mortality and comparing to the base actuarial models the statistics for a death in any given year of life are easy to look up as a 43 yearold my chances of dying before my 44th birthday run at around 600 to one ,inotherwords if you had a room of 600 males celebrating thier 43rd birthday party on average you would need to buy one less cake for a years time. Thats irespective of any health or lifestyle factors. What i wan5 to know is for my current 1 in 189 risk is that of pml in the next year,month or lifetime?

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    2. tysabri for 7 years jcv positive with stratify index of 2.6 46 years old no flare ups in 6 years..risk of pml is being told to me as 1 in 70 chance ???? very confused on life changing decisions

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    3. I believe those odds, please be in the care of a competent neurologist.

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    4. She seems very in tune with things, but really confusing with answers to my questions on an attack that is inevitable . also with the pml info when the blood brain barrier is no longer there from the tysabri. i have done al great deal of personal research before i make this decision to change, but im not sold on not getting the pml even if i change.

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  2. Also, once a person tests postive for JC virus, is the titre level likely to vary over time?

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    1. tested postive in Jan 2014

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  3. It's not just how much risk you are willing to take that is personal, it is what type of risk bothers you most. A parent may be most afraid of not being able to care for a child. One patient might be more afraid of Gilenya's cardiac issues where another finds the thought of an additional brain problem, PML on top of ms as much more intimidating than a heart attack.

    When you add the doctor's risk aversion, it's possible that they are more afraid of harm from treatment (something they were part of and responsible for) than they are afraid of harm from the course of the disease. They also may just not realize how thoroughly perspective on risk changes when the cost of doing nothing, not taking a risk, is likely to be bad disability even if that is decades down the road. Also, if someone is doing well now, they may be considering the price of the mental harm, the anxiety, if they push for risky treatment and argue for it using problems that could come much later.

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    1. 'additional brain problem'

      that is quite an understatement!

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    2. " it's possible that they are more afraid of harm from treatment (something they were part of and responsible for) than they are afraid of harm from the course of the disease"

      - I think that's very true. The harm from treatment could come suddenly and soon, and they will be responsible for it, and they will have to treat it.


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    3. But, for the patient, the experience of harm from the disease could easily be much worse than that harm from treatment. A quick death is not the worst outcome in life and ms can evolve into a fully conscious paralytic prison without speech. A doctor should not be weighing his or her risk of treatment failure more heavily than a patient's risk of a bad outcome from organic disease. But, I wrote the previous post and I can easily see how such choices could be made. Especially with ms, the doctor in question could be retired before the costs of 'conservative' treatment become apparent in the disease of the patient. No longer the doctor's problem.

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    4. Based on the Biogen-Idec NEJM paper the analysis is a retrospective analysis. For example, the number of cases who have developed PML after say 48 months (numerator) divided by the number of cases who have been exposed to the drug for 48 months or longer (denominator). I have copied the statement from the Bloomgren NEJM paper that describes this. However, as the number of at risk people in the denominator is changing due to JCV+ MSers coming off the drug it is difficult to give you a personalised figure for the next 12 months. I suspect the actual prospective or future risk of you developing PML if you are JCV+ve is in reality higher than the quoted retrospective figures.

      “Estimates of the incidence of PML since the reintroduction of natalizumab into the market were made on the basis of the number of confirmed cases of PML at the time of this analysis and the postmarketing exposure to natalizumab through February 29, 2012. We calculated the incidence of PML in each time period (12-month treatment intervals) by dividing the confirmed number of PML cases among patients treated with natalizumab during that time period by the total number of patients ever exposed to natalizumab during that same period.”

      http://www.nejm.org/doi/full/10.1056/NEJMoa1107829#t=article

      I hope this makes sense?

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    5. Dr. Giovannoni, would you be willing to further describe the PML symptom of "changes in mental/cognitive status"? I cannot find any examples of what this might look like in an actual case. Could a patient present with isolated incidents of cognitive decline, returning to a "relative normal state" in the mean time or would it be a steady decline with no relapses? I can't post pictures of this, but in my mind, I'm imaging the graphs that depict the difference between RRMS and PPMS, except the y-axis would represent mental status instead of general disability and obviously the x-axis would be a much shorter period of time.

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  4. My daughter died aged 28 after 53 infusions. Shingles contracted after the 53rd and a second unidentified catastrophic fatal infection within 5 months of the 53rd.

    The prescribing neurologist responded to shingles with the statement he had 'no concerns about the rash with regard to medication '
    He requested an elective admission to his care after a DNR order had been issued in our home, my daughter did not consent to his request .Biojen Idec medical expressed an interest in following up my daughters death with the parliamentary health ombudsman.

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    1. RE: "My daughter died aged 28 after 53 infusions."

      I am very sorry to hear your bad news. I have nightmares about one of my patients developing PML. I know the first person to develop PML in our centre is just around the corner, which is why we are trying to get all our patients at risk of PMl off natalizumab. It really is a race against the clock.

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  5. Regarding your getting patients off natalizumab. My daughters neurologist told the PHSO that my daughter ' had sadly died because her treatment was withdrawn' further more ' withdrawal of this drug leads to reactivation of MS to pre-treatment levels '. He didn't share these tit-bits with my daughter, he expressed 'no concern' about her shingles and she elected not to continue infusions on the advice given in her obsolete patient information( Prepared 07 ) she carried an obsolete alert card as well. I hope you see fit to counsel your patients to risk and it never looks very professional to phone saying hi and how about you come see me after you have classed your patient Moribund: fatal processes progressing rapidly.

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    1. Re: "Regarding your getting patients off natalizumab."

      The following are two post about switching patients from natalizumab onto other drugs. This is currently how we do things within Barts-MS. We are very aware of the rebound and try and prevent it happening. The biggest problem we have at present are women wanting to stop natalizumab to fall pregnant. Some neurologists are letting them fall pregnant on natalizumab before stopping the drug, others are continuing it through pregnancy, others just stop the drug and hope for no rebound.

      http://multiple-sclerosis-research.blogspot.com/2014/05/clinic-speak-switching-from-natalizumab.html

      http://multiple-sclerosis-research.blogspot.com/2014/02/clinic-speak-switching-from-natalizumab.html

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    2. Well you run a tighter ship within Barts-MS than here in the sticks that's for sure. Hands on with the live patient, impressive.

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