Wednesday, 29 October 2014

Extended interval dosing of natalizumab

Bomprezzi R, Pawate S. Extended interval dosing of natalizumab: a two-center, 7-year experience. Ther Adv Neurol Disord. 2014;7(5):227-31

BACKGROUND:The enthusiasm for natalizumab, a highly efficacious agent in the treatment of multiple sclerosis (MS), has been tempered by the risks of progressive multifocal leukoencephalopathy associated with its use, and strategies to minimize those risks are of great interest. Extended interval dosing (EID) has been proposed as a way to maintain the efficacy of natalizumab while reducing exposure to it. We reviewed a cohort of patients who received natalizumab at 6-8-week intervals instead of the typical infusions every 4 weeks with the goal to assess if patients on EID had an increase in clinical relapses.
METHODS:This is a retrospective review of all patients with MS treated with natalizumab at two MS centers where patients were offered the opportunity to switch to an EID every 6 or 8 weeks.
RESULTS:A total of 361 patients received natalizumab for 22 ± 13 months (minimum duration 6 months). Of these, 96 patients received EID natalizumab at some point for 20 ± 11 months (minimum duration 6 months). Over the study period, there was no significant difference between the relapse rate in the monthly dosing (13%) and the EID (13%) groups of patients.
CONCLUSION:Natalizumab is effective in controlling MS as very few clinical relapses were observed in our dataset. We found that EID did not compromise the treatment effect as measured by relapse rate and no significant breakthrough disease activity was observed. EID is an optional regimen for maintenance natalizumab therapy, but prospective studies are warranted to determine its efficacy.



Tysabri is typically administered every month, but this study looked and found that there was no more disease breakthrough if the interval between injections was extended to 6-8 weeks.  We know that from switching tysabri that disease returns once you stop and it takes a few weeks for the tysabri to get out of your system. 

If we wanted to be scientific about this, as we know that tysabri works because it blocks CD49d/VLA-4 on white blood cells. If we added a labelled antibody against CD49d and it could not bind because tysabri is working, with time new CD49d would be produced and then the labelled antibody would bind. Once a certain level of free CD49d is present, disease can return. So you could check this with a blood sample. It would take about 30-40min for me to do it and you could know if you are an individual you removes tysabri from the system quickly where EID may not be appropriate or someone who does this slowly and where EID may be more appropriate. The cost o the extra tests could be offset by reduced drug cost.However, its in the Interest of Biogen to sell you as much drug as possible. Look at Teva...they spent years telling you to inject daily yet once their patent for Copaxone runs out they come up with a formulation that only requires 3 times a week injections. 

10 comments:

  1. I'd really like to see something more than the supposition that "... Teva...they spent years telling you to inject daily yet once their patent for Copaxone runs out they come up with a formulation that only requires 3 times a week injections." Frustrated patients already tend to replace understanding of MS with conspiracy theories involving doctors and pharmaceutical companies. It would be helpful if you were to supply evidence to support these kind of propositions.

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    1. Hey it's an opinion. You can make your own mind up but as the overarching priority of pharma is to make a profit (and also to lengthen the profitable life of their wares), knowing this can inform you as to their strategies/announcements.The fact that Teva jacked up the price of copaxone before it's patent expires shows where their priorities lie to me but again that's just my opinion. Maybe you know different?

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    2. I agree MD. Really big pharma wants to make big profits for its shareholders and for as long as possible. It's not black and white thinking thereafter but this fact (how all business works) must always be borne in mind. I'm not a conspiracy-minded person, but I'd be an idiot not to consider the profits and shareholders position in many pharmaceutical decisions/strategies.

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    3. That's the point. Where you suppose gouging was going on, I suppose there my have been a legitimate reason for the price hike. But we both need evidence to back up our suppositions. I'm an MS'er with no connection to the pharmaceutical industry who finds that other MS'ers are extremely suspicious and likely to believe any conspiracy involving doctors and pharmaceutical companies. It benefits no one, including the truth.

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    4. The legitimate reason would appear to be to sqeeze the last drops of profit out of a drug that was not only about to go off patent but is now superceded by the newer DMTs. You will of course never get them to admit that and of course any evidence gathering will be impossible as the information is "commercially sensitive" other than a grand jury/senate hearing in the US which are now being done to question the level of drug pricing.
      The evidence is there in their actions witness the abrubt withdrawal of Alemtuzumab by Sanofi/Genzyme from the market to relaunch as Lemtrada (at a much higher price) leaving those who were on a course of Alemtuzumab high and dry until pressured to relent by many (including this blog and its members).
      Sometimes conspiracy theories are justified, just look at the complete failure of any market in MS drugs, where there is no competition on price but rather a collective strategy to charge what historically the market will stand, which looks to me like a cartel.
      This is now being taken seriously in the US, I mean tens of thousands for Tecfidera, when it's cheap as chips to make?
      the pharma market is broken and in urgent need of reform.

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    5. It all depends on how you define 'legitimate reason'. I'm sure there are many reasons that pharma can come up, that are legitimate to them. But bottom line -for me- is cui bono on this. That doesn't mean I believe the moon landing was shot in a TV studio or that some politicians are alien lizards (a la David Icke) tempting as the latter is ;).
      I have to disagree with you on your assumption that people with MS are 'likely to believe 'any conspiracy involving doctors and pharmaceutical companies'. MD gave his opinion, you can agree or disagree or sit somewhere in the middle, that's up to you and everyone reading this post.

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    6. Should we do a post on the price of copaxone in USA....sure I can't be bothered

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  2. Show me the memos concerning collusion in the pharmaceutical industry.

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    1. If you have access to the computers of the pharma industry to see their memos then you are probably working for MS pharma..you could have MS and still go on the dark side.

      Show me the price competition between the pharma and I won't suggest to you an effective cartel of price fixing:-).

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    2. Well we don't have the power to request this as freedom of information does not extend to commercially sensitive areas but I always go on the principle of "If it looks like like a duck, walks like a duck and quacks like a duck, it's a duck". You are perfectly free to think it's a cat, should you so wish.

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