Wednesday, 15 March 2017

#NewsSpeak: another eagle has landed - daclizumab

Finally people with MS get a new treatment option with some interesting attributes. #NewsSpeak #MSBlog #Daclizumab

Good news for pwMS living in England; NICE have deemed daclizumab to be cost effective to treat pwMS with more active MS and in whom alemtuzumab is contraindicated or otherwise unsuitable. As always the drug has been made available to the NHS at a discounted price. Having daclizumab as a  treatment option widens the choice for pwMS, in particular pwMS at high-risk of PML on natalizumab. Daclizumab is given monthly by subcutaneous injection. The downside of daclizumab is the need for monthly liver function tests to monitor for inflammatory liver disease that occurs in ~2% of treated subjects. However, pwMS who respond to daclizumab do well and tolerate the drug without major problems. Daclizumab has an interesting mode of action and is not overtly immunosuppressive that may make the drug appealing to some pwMS. 

Patient access schemes, or secret discounting to the NHS, is something the US Republican senators are very unhappy about. In short the Republicans are furious about the fact that US taxpayers are subsidising drug development, and drug pricing, for rich European countries, in particular the UK. They are very unhappy with the deals Pharma are doing with the NHS via NICE. I have been told that high on the US agenda when the UK tries to negotiate a trade deal with the USA post-BREXIT is the abolition of NICE and patient access schemes. To the neoliberals in the USA NICE and patient access schemes are anti-competitive. The question is what will our government be prepared to concede to the US to get a trade deal in place? Will they sacrifice cost-effective drug pricing? I sincerely hope not, we really need some counterbalances to excessive drug pricing. An example of this that will test NICE's mettle is Biogen's price for Spinraza a new treatment for a rare genetic disorder called spinal muscular atrophy ($750,000 for the first 6 doses). SMA is in general a fatal disease and hence will be a very emotive HTA (health technology assessment). Will NICE deem this drug to be cost effective for the NHS? Will NICE get a discount from Biogen as they have done for daclizumab?  

The interesting thing is that Obama created PCORI (Patient-Centered Outcomes Research Institute) to try and do the same thing for the US as NICE has done for the NHS. Will the Republicans close down PCORI? 



CoI: multiple

22 comments:

  1. Is daclizumab better than tecfidera and fingolimod? If your a no responder to tecfidera is daclizumab likely to work or.should on take the riskier path of alemtuzumab straight away?

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  2. The MS Society state "It will only be available to people who are unable or unwilling to take alemtuzumab."
    Unwilling... so does that mean pwMS can choose between alemtuzumab and daclizumab? if they meet criteria.

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    1. Daclizumab is highly effective drug like Fingo or offlabel cladribine. Seems to be more effective than DMF and Teri and less than Nat, OCR or Ale.

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  4. I would classify Dac as a highly-effective drug. Please note it is horses for courses; some people may respond better (NEDA) to one, but not another class of drug. The real challenge is finding out who is more likely to respond to drug x so that we can get them NEDA ASAP.

    Some one may breakthrough on alemtuzumab and go onto to Dac and do very well. It is having the option of Dac that makes the difference. As it is not associated with significant lymphopaenia it may be the drug of choice in people with lymphopaenia on another DMT.

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    1. Prof G!
      Has it any effect on B cells and CNS abnormalities?

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    2. Memory B cells have CD25 and they are depleted when daclizumab is used in transplantation

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  5. Aw, my homeboy Trump hates NICE with a passion. Sky News has reported on this. He has allegedly targeted it as to be wrecked asap.

    There are three ways to fund healthcare: Insurance, Tax, Cash. In this country's desperation to be all-American and thick, Tax is going to be massively undermined as an ideal.

    Britain is an embarrassment, bredrin. We have become idiots. All we want is to watch crappy American films that are meaningless and eat their inspired unhealthy junk foods. And now we want an unaffordable and unfair health system like theirs too. It is depressing.

    Gotta go. Under the cosh. Love you all. Kiss you on both cheeks xx.

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    1. Ah... So you want look towards the political equivalent of Neanderthal man in qualifying intelligent decisions and/or examinations of complex systems.

      How eggceptional, hard or soft boiled.

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    2. You've lost me, Ms Unites. Didn't understand any of what you said.

      Dre is a legend!

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    3. A am Dre aware and can easily parse diatribe.

      His statement is that NICE is disliked by President Trump is immaterial. Had he actually paid attention to US credible news he'd realize very fast the current US administration is at best all over the roads and worse may take the rest of the civilized globe with it.

      In as far as funding of health care goes the global landscape needs MUCH needed reforms from top to bottom. As long as enormous amounts of money are in the mix its rather difficult to accomplish. In fact, the moment any human services become subject of business and revenues things tend go southwards downhill as disparity comes into play in respect to socio economics. Sad but true.

      The US health care system is a hybrid system very unlike that of Canada or Britain and subject to a lobby arguably more powerful than banks. The insurance lobbies are extremely powerful for numerous reasons.

      An example: http://www.dailymail.co.uk/news/article-4145970/Company-increased-price-infant-epilepsy-drug-85000.html

      I've taken Acthar Gel for an MS exacerbation, billed my insurance carrier $38,000 for five injections. By weight, it may be more valuable than gold.

      The care systems are round robin machines and at all levels of said systems costs rise across the board. The snowball just gets larger and larger. Imagine the same levels of increases in say energy, formative schooling years or even food.

      Dre mentions American food. Most companies that provide garbage food are not owned anymore by US interests, in fact, a large portion are owned by European interests.

      In the USA and presumably much of the civilized world one basic problem has occurred. Public service became business. There was a time when public service meant just that. One works in the public interest and could expect pay and/or benefits that were NOT commensurate with corporate or even not businesses. Now, thats flipped at least in large part in the USA.

      Unions were despised in the USA. Now nearly every public service "industry" (keyword) is unionized. Dont pay teachers/educators what they like, austerity budgets go into place so they keep the pay rate and then hack at services provided in education.

      MANY people here in the USA believe that government needs to be run like a business which shows that they do not have the slightest clue about what they speak of. Government HAS been run like a business in oh so many respects and it is in large part WHY the US now is in the dung it is in. Populations are treated as customers of the system(s) .vs. citizens of said nation.

      Lobbyists and money direct said system(s) just as is the case in businesses working with other businesses. The largest difference is the goal of business is to run profit. Instead, we have a business that relies upon a population to near fully fund it. That worked just fine until the "operate like a business" filtered downwards into states, then local governments. The financial stress placed upon the customer (individual and/of families) overwhelms their ability to stabilize and capture the American dream.

      These systems are ever so complex, they cannot be understood via an hour, 8 hours, 108 hours or perhaps even 1008 hours of intense study and information.

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    4. There are other disparities in comparing the United States to say Britain. In the USA costing of near anything depends upon where one resides. A $100,000 dollar home in Upstate NY State will readily run $400,000 or more in Southern California. Place it on a beach and you can add nearly a million to that number.

      Comparing Britain to the USA is completely moot. One is an island less than the size of California and most of California is not highly populated. Britain has 64 million people. California alone has 38 million, New York, 20 million, Florida 20 million. Three states encompass more people than all of Britain and socio economics vary not only per state but even within said states. Living in New York City, Long Island is a whole whole lot more expensive than say Upstate NY.

      It is simplistic thinking to say, "Taxes, Cash and Insurers" are the only ways to fund a Health Care system.

      Before even considering options in funding such a complex system costs of all aspects of said system(s) need get properly balanced and/or regulated. This can only happen (IMHO) at the interfaces of the varied portions of said systems. Doing this is extraordinarily complex at every existing interface.

      Further, attempting to do so without completely smashing what is existing in the process makes changes even more complex. Health Care is not a do this, that and this and all gets fixed. Its steering a giant. Like trying to steer a giant ship that only has 2 degrees of rudder movement. If one steers 4 degree's than the current care begins to have people, patients, physicians, opportunities, research, pharma, insurers fall off the side of the deck and drown.

      Even worse, micro-evaluation of all aspects yields both problems and solutions. However, by the time these are all pieced together the time in doing so has already negated numerous amounts of said evaluations.

      Some people say, "Let the systems implode. Then we can start from scratch."

      Generally speaking the people saying that are not living with say a chronic disease such as Multiple Sclerosis, Lupus, Cystic Fibrosis etc.

      These are not diseases they caused by eating Twinkees.

      Which is more at fault? A person who chooses the construction trade and who's knees and hips are shot due to a lifetime of said work? A person who chooses poor dietary and exercise regimen's and thus ends up with coronary disease? A mechanic exposed to noxious fumes? Or, a person who did nothing yet ends up with MS, Lupus to name just a few?

      Which patient should pay more? How is any of it proofed?

      Healthy people tend to look at costing due to those who are ill and yell about it. However, when they become ill with say MS and bare no faults as to why... Then the story changes, fast.

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  6. Totally of subject, recent research at Queens shows T reg cells initiate myelin repair. Given Alemtuzumab works by increasing the number T reg cells and shown to reverse disability. CDI instead of CDA. Is this another reason why Alemtuzumab should be considered above all other treatments?

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    1. I am waiting to recieve a guest post by Dr Fitzgerald, which she said she would do before her trip today.

      Next point. Alemtuzumab increases T reg numbers is a falicy started by Cambridge and perpetuated by everyone else.

      We are so desparate these days to have a mechanism whereby Tregs call the shots and yes if we look at percentages T regs of the CD4 population increase from about 3.5% of CD4 T cells up to 13-14%.
      So this is why alemtuzumab stops MS. Great.

      Now go and read the paper and look at the actual data (see Cox et al. 2005. it is open acccess https://www.ncbi.nlm.nih.gov/pubmed/16231285
      Page 3333 figure 1 A tells you how many CD4 cells are in the blood, first paragraph, Page 3334 last paragraph left had side gives percentage of T regs 3.7%. Now there it gives the percentage of T regs after alemtuzumab 13.5% (yeah increase), now read top paragraph pg 3335 to get absolute cell counts. So do the maths and so after alemtuzumab we go from about 30,000 CD4, CD25high T reg cells per mL of blood down to 2 cells/mL yes that is two. So a big increase I think not, especially when T reg cells often work by cell cell contact.

      Massive actual decrease, bad science, and more likely to be the cause of the problems of autoimmunity with alemtuzumab.

      Alemtuzumab is a very effective drug but it comes with baggage, think about things abit differently and maybe you can reduce the baggage.

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    2. Yes ok in terms of absolute numbers there is no increase in any numbers of white blood cells. But isn't the ratio just as important. For instance in football match you have 100000 supporters and 3000 cops to keep order. After alemtuzumab you have 10000 supporters and 3000 cops keep order. That's still more cops to keep order even though absolute numbers are lower. My scientific training has taught me ratios are just as important. But will defer to you guys. Let's hope Dr Fitzgerald advance their new findings to treatments sooner than the normal 15 years from lab to fda approval.

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    3. However, as we have mentioned the number of cops is massively reduced and quite rapidly there is not only a repopulation of B cells (regulated by the T regs which remain hugely reduced in contrast to the B cells) but a hyper-repopulation where you end up with more than you started with before treatment and the cells responsible for regulating them are in ratio still greatly reduced, which to us lays the ground for the development of secondary autoimmunity.

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    4. Crikey. Y'know I love the way you two mice delve right in, look at the actual data and cut out all the spin. MD I reckon you must be well known to all your students for saying 'read the paper' and 'look at the data' they're have probably been bets placed on how many minutes into the lecture (or whatever you call them these days) before one of these phrases is uttered ;-) :-D

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    5. In addition and most importantly 'don't believe all that you read, look for the flaws, you will usually find some'. It comes with experience. MD uses the famous salt paper as an instructive example.

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    6. Guest post tommorrow

      Maybe I will write some posts so we can go through this properly to Head teachers annoyance......bit but bit.....it'll be the dentist prodding that cavity "saying is it safe". This is because the implications are there for a missed solution to autoimmunity and a host of other things you can find out by reading, reading reading, if you know where to look.

      Hey I'll even write a paper on it. Will the referees buy it?

      P.S. The standard phase is usually pure Yorkshire
      "What a load of b******s"...Not very scientific I know, but conveys the contents quickly:-)

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    7. Not sure if the editors would like it :-). After all they are the ones who let the stink pass as published science.

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  7. I was speaking to my nurse about this today and she showed me an email from the neuro advising patients that have previously had lemtrada would not be eligible for this drug due to the contradictions. Is this correct? Thanks

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