Wednesday, 11 December 2013

Is natalizumab worth the Risk?

What does a QALY mean to you? #MSBlog #MSResearch

"The health economic analysis suggests that natalizumab is cost-effect even with the risk of PML built into the model. What do you make of their claims?"

"Health economists reduce the value of life down to a simple metric called a  QALY or quality-adjusted life year. A QALY is a measure of MS disease burden and includes both quality and the quantity of life lived. The QALY is based on the number of years of life that would be added by an intervention, in this case natalizumab, fingolimod or interferon-beta. Each year in perfect health is assigned the value of 1.0 down to a value of 0.0 for being dead; a score less than zero is worse than dead. If the extra years could not be lived in full health, for example if the MSer had to use a walking aid ir wheelchair, then the extra life-years are given a value between 0 and 1 to account for this."

"Would you be prepared to live a shorter life of better quality than a longer lifer of poorer quality? In other words would you like to feel and function normally on natalizumab for 4, 5, 6 or 8 years and then die or become disabled from PML? I suspect not, which is why you are relying on us to de-risk this decision with other options or treatments for PML. Or would you like to live 20,25 or 30 years, not feeling well and becoming disabled? Probably not, which is why you are relying on us to develop better treatment algorithms and risk predictors to prevent this. Health economic analyses are the here and now and do not take into account the innovation treadmill that is turning continuously. Things may be what they are today, but they will not be the same next year or the year after. This is why I am such an optimist when it comes to the future. 

"This type of health economic trade-offs, which the NHS uses, make little sense to the individual with MS. Nothing is certain at the individual level. As a neurologist all I can offer is advice and relative risks. No gambler goes into the casino to lose money; they go into the casino with the intention of winning money despite the statistics showing the majority of gamblers end up losing. No MSers goes onto interferon-beta or glatiramer acetate to do badly, despite the fact that the majority given time on these drugs will do badly. No MSer goes onto natalizumab to develop PML, etc. This is why we need to individualize treatment decisions, actively monitor, change and escalate treatments in a timely manner. This why the treat-2-target of NEDA meeting this week is so timely."

Epub: Walker et al. A benefit-risk analysis of natalizumab in the treatment of patients with multiple sclerosis when considering the risk of progressive multifocal leukoencephalopathy. Curr Med Res Opin. 2013 Dec 2. 

Background: Natalizumab is a highly effective treatment for patients with relapsing-remitting multiple sclerosis (RRMS). Treatment with natalizumab has been associated with progressive multifocal leukoencephalopathy (PML), a rare yet serious disease of the brain. Published studies have quantified the PML risk by the presence of anti-JC virus antibodies, previous immunosuppressant use, and duration of natalizumab treatment. 

Objectives: The aim of this analysis was to evaluate the net benefits and risks for patients with RRMS receiving natalizumab treatment compared with fingolimod, interferon-β, and no treatment across PML risk sub-groups. 

Research design and methods: Based on previously validated MS model structures the impact of treatment on quality-adjusted life years (QALYs) was assessed. Natalizumab-treated patients were classified by PML risk sub-groups and analysed separately for short-term (2 years) and long-term (20 years) time horizons. 

Main outcome measures: Main outcome measures included total QALYs by PML risk sub-group and the increase in PML risk associated with natalizumab treatment which offsets the quality of life benefit of comparator treatments.

Results: Results showed higher QALYs with natalizumab versus all other comparators across PML risk sub-groups over both time horizons. For the QALYs of natalizumab to equal the QALYs of fingolimod, interferon-β, and no treatment, the risk of PML would have to increase 4.6-84.2 times, 24.0-444.3 times, and 5.7-106.1 times, respectively (short-term), and 1.4-123.4 times, 1.5-138.3 times, and 2.2-193.7 times, respectively (long-term).

Conclusion: This study shows that natalizumab generates the most net health benefits in terms of quality-adjusted life years compared with fingolimod, interferon-β, or no treatment, even when the risk of natalizumab-associated PML is taken into consideration. This study is limited by the availability of published data around natalizumab-associated PML, as well as the constraints of the model used to conduct the analysis.



Introduction: Natalizumab is a highly effective monoclonal antibody used for the treatment of multiple sclerosis (MS). It reduces relapses, delays the onset of disease progression and improves disease outcomes in relapsing-remitting MS. However, treatment with natalizumab is associated with progressive multifocal leukoencephalopathy (PML), a severe opportunistic brain infection with John Cunningham virus.

Expert opinion: Natalizumab is a very effective therapy for MS and has shown tremendous results in reducing the disease activity and improving patients' quality of life. Serious adverse effect such as PML warrant extreme caution and heightened clinical vigilance while prescribing the drug. If used with prudence, the drug can be instrumental in treatment of patients with inadequate response to the first-line medications.

CoI: multiple

4 comments:

  1. Surely natalizumab is more risky than alemtuzumab? Why then has the FDA takes such a hard line on alemtuzumab. If they are so worried about risks they should withdraw nataliuzmab from the market.

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    1. Nataluzimab is made by an American company and Alemtuzumab isn't? Perhaps I'm being overly cynical?

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  2. My recent blood test showed that I was positive for JC virus so my doctor and I decided that I had a good run with Tysabri, but because of the increased risk of PML I am being taken off of Tysabri after 5 years to try Tecfidera. When I started taking my monthly infusion of Tysabri in December 2008, I felt my world falling apart and have since had my quality of life improved greatly. If I did not have the increased risk, I would still be getting it and depending on the outcome of this pill, I may still. I am and will continue to be a fan of Tysabri.

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  3. PML is a bloody terrifying outcome and the pharma company and doctors who failed to communicate that risk early on have a lot to answer for. That said, if the new risk mitigation figures are accurate, it now seems a valid choice for some. Given the history, I won't trust that particular company with my health, regardless.

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