Doc Knows Best. It’s only your risk Reasons to switch from natalizumab

Krämer J, Tenberge JG, Kleiter I, Gaissmaier W, Ruck T, Heesen C, Meuth SG. Is the risk of progressive multifocal leukoencephalopathy the real reason for natalizumab discontinuation in patients with multiple sclerosis?
PLoS One. 2017 ;12(4):e0174858.

BACKGROUND:Progressive multifocal leukoencephalopathy (PML) is one of the major risks of natalizumab therapy. Despite introduction of the currently employed PML risk stratification algorithm, the incidence of natalizumab-associated PML cases is not decreasing.
OBJECTIVES: We addressed the following questions: How do natalizumab-treated multiple sclerosis patients and their treating physicians assess and deal with PML risk? Is PML risk the real reason for natalizumab discontinuation?
METHODS: 699 natalizumab-treated multiple sclerosis patients and 99 physicians were included in this prospective observational study. Questionnaires were completed at 5 different time points. Patients were stratified into 5 subgroups according to the presence of PML risk factors (prior immunosuppression, anti-JCV antibody status, treatment duration). Patients with prior immunosuppression (n = 30, treated by n = 7 physicians) were excluded from analyses, because patient numbers were too small. Patients’ anti-JCV antibody index was not considered because data recruitment ended in 2014. We examined the relationship between different patient- and physician-related factors and patients’ discontinuation of natalizumab.
RESULTS: Patients of all subgroups and physicians assessed the PML risk as low. Overall patient adherence to natalizumab was high (87%). Only 13% of patients discontinued therapy. Natalizumab treatment cessation was associated with different patient- and physician-related factors (physicians’ assessment of general PML risk, number of treated patients per year, natalizumab treatment duration, relapses during the course of study) upon which only physicians’ judgment on treatment continuation, patients’ perception of personal PML risk, and JCV seroconversion showed significant relationships.
CONCLUSION: According to the currently employed risk stratification algorithm, the objective PML risk probably doesn’t play a dominant role in a patients’ decision to continue or stop natalizumab treatment. The decision-making process is rather guided by subjective views and experiences of patients and treating neurologists. Treating physicians should consider this discrepancy in their advice to improve the risk-benefit-ratio for the individual patient.

Last week ProfG was in Germany and was rather shocked to find that Neuros there paid no attention to the desire to maintain no disease activity, thinking it was some pharma spin and took the path of least monitoring. So in this paper, I guess it comes with little shock that there is little apparent thought given to switching away from natalizumab, based on empirical JC virus, previous immunosuppression, JC titre (antibody levels) and time on drug but on experiences of neuros and patients. 

I wonder if Neuros in USA would agree with the approach

Maybe ProfG would give his views, but I was at a meeting last week when the risk of PML was being discussed and this was at the forefront of the the reason to switch

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  • I learnt yesterday from a very well-informed lay person, who works in advertising, that consultants/specialists/MSologists are never wrong. Passivity is the name of the game and that in general people with a disease still hold their view that their neurologist knows it all and that they would never dare to question their authority. Only very few patients ever question the decisions of their consultant.

    How do we tackle passivity and activate pwMS to ask the right questions?

    • I used to be passive like this but I think it was more to do with being very naïve about MS, treatments and the healthcare system in general.
      My neurologist is an MS neuro. I have noticed they have got a few things wrong but that's looking back with hindsight.
      I've got a list of questions for my neurologist about decisions about my care.

  • MS symptoms can be alarming, making us feel useless, vulnerable and at it's mercy. Perhaps to acknowlege that the person we look to for reassurance and help, can't or chooses not to provide it, is just too much on top of everything else. Far easier for some to bury their heads in the sand and take whatever neuros say as gospel.

    'How do we tackle passivity and activate pwMS to ask the right questions?'

    Shouldn't the question be 'How do we train neuros so that patients' trust is not misplaced?'

  • The reason why some of us pwMS are keeping passive is that if we question our care we may be seen sometimes as trouble makers.
    I have experienced this and it has not been nice. I have noticed a few other pwMS mention this too. I would love to say my all care has been great but that would not be the truth. Some elements of my care have been good.

    I am learning to be diplomatic when I question my care. In a feedback sandwich style sometimes. Choosing my words carefully.

  • A PwMS has been NEDA on Tysabri for several years but is JCV+ with a high titre. Statistics give them a 1% risk of PML. They are told this means they should switch to another DMT but they have some questions…

    • What is their risk of having a severe relapse in the washout period ?
    • What is their risk of having health problems from ongoing steroids during the washout period ?
    • What is their carryover PML risk to each of the alternative DMTs ?
    • What is the risk that they will be a suboptimal responder to each of the alternative DMTs ?
    • What is their risk of serious side effects from each of the alternative DMTs ?

    Does knowing a number for a statistical risk make it easier or harder to make a decision than not knowing a statistical risk ?

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