Word reaches me of movings afoot in London that are not unexpected. It seems that the Dept. of Health and other interested parties are engaging with pharmaceutical companies and ‘suggesting’ that they may want to investigate the possibility of developing a 1mg or 2mg tablet of B12 that could be prescribed by doctors to treat Pernicious Anaemia.
Now, as I’ve said, this isn’t unexpected. I know that one of the results of our online petition at the Welsh Government was that the Chief Medical Officer advised that if patients needed more frequent injections then they should supplement with oral tablets. The problem is that the tablets that doctors can currently prescribe in the UK are nowhere near 1mg in strength, I believe they are 50mcg and the suggested dosage is 50-150 mcg taken between meals – so for 150mcg you would take 3 tablets. Remember there are 1,000 mcg in a mg. The BNF suggests the use of oral tablets to replace any dietary deficiency in B12 but does not recommend them for treating Pernicious Anaemia – that should be treated with injections.
So, why are the powers that be encouraging pharmaceutical companies to produce 1mg tablets to be licensed so that they can be prescribed?
It’s a long and convoluted story that involves several agencies and I will do my best to explain the process although I will have to confine my report to the situation in the UK.
Firstly, you have to understand that in most cases, the UK Health Authorities (comprising the Dept. of Health, Royal Pharmaceutical Society, Royal Society of Medicine and various other government departments) do not commission the development of pharmaceutical products – medicines. There are exceptions to this but in general it is left to Pharmaceutical companies to develop medicines that can be used to treat diseases – like Pernicious Anaemia. It was pharmaceutical companies who first developed the liver injections during the late 1940’s and who then went on to develop and produce artificial B12 injections. However, developing these products, as challenging as they often are, is only the beginning of a long journey to make the medicine available to the public via their doctor. Once developed, the new product has to pass the strict quality controls that are set out by the Medicines and Healthcare Products Regulatory Agency (MHRA).
These are the people who will approve or reject the newly developed medicine; and they will take some convincing. Only after the new drug has been subject to many years of testing on volunteer patients, and a comprehensive investigation into any side-effects and any other possible complications has taken place will the evidence be placed before the MHRA. The MHRA is composed of various departments made up of highly skilled and knowledgeable doctors, pharmacists and other scientists. Visit their website and you will begin to understand the scale of the work that the agency is involved in. It’s they who are currently involved in the evaluation of e-cigarettes whilst at the same time producing new standards for blood transfusions. And it is the MHRA who will eventually be responsible for deciding whether any pharmaceutical company’s new 1mg or 2mg oral tablet will be safe to treat Pernicious Anaemia. The decision shouldn’t be too difficult as we know that 1 or 2mg tablets are used to treat the disease in other parts of the world.
The precedent has been set.
All of this was explained to me when I met two representatives of the MHRA two years ago, (their offices, incidentally are a nightmare for vertigo sufferers like me – it’s all wall to wall glass – even the floors). So what’s the thinking behind replacing the time-honoured treatment of PA by injections with tablets?
In a word it’s money.
Let’s go back in time to the mid 1920’s when the Nobel prize for medicine’s recipients had received the honour for discovering that patients with Pernicious Anaemia could be kept alive by giving them raw or slightly cooked liver. It was a time when the smell of searing offal permeated hospital wards and providing patients with a varied diet was a challenge to hospital caterers. Imagine the joy on the faces of patients when they were told that the days of eating raw liver were over and they could instead have a (probably painful) injection of liver essence instead.
‘What’s for lunch? These patients are on a Pernicious Anaemia hospital ward where they were kept alive by eating just cooked or raw liver’
And imagine the further joy when a decade or so later they were provided with a monthly injection of ‘grown’ B12. Happy days at last.
Now we know that the British National Formulary (BNF), that little booklet that is produced twice a year by the Royal Pharmaceutical Society and the Royal Society of Medicine which acts as a reference for doctors to consult in order to treat patients correctly, used to recommend a 1mg injection of Hydroxocobalamin every month when the injection was introduced at the start of the 1960’s. For some reason, and I can find no scientific basis for this, that recommendation was changed in 1974 to an injection every two months and then in 1984 to every three months. When I met with the editor of the BNF a year or two again she told me that any change in the treatment would have been based on ‘evidence based research’. Yet I can find no evidence of this. I’m not calling anyone a liar – I just haven’t been able to find any papers that the decisions to change the treatment was based on. Some people say that because Hydroxocobalamin replaced Cyanocobalamin the treatment was changed because Hydroxocobalamin is retained longer by the body which is a highly suspect argument that I go into in my last book and so I won’t repeat it here.
Anyway, the fact is that some people manage perfectly well on a 1mg injection every three months but others, and the vast majority of the PA Society do not, and they feel a return of their symptoms, or their family and friends notice a return of their symptoms long before their next injection is due. Now, let’s state some facts: we are trying to recruit people to take part in a research project who manage perfectly well on their three-monthly regime.
We have only been able to recruit 6 people from our membership base of over 7,000 who manage well on their three-monthly regime. Just 6!
And three of those ‘know when it’s due’ indicating that they are right at the edge of their treatment envelope.
The Evidence that oral supplementation can be used to effectively treat Pernicious Anaemia is weak. There, I’ve said it, and I’ve probably annoyed some people by so doing. But the fact is that the Cochrane Review of the use of Oral tablets to treat PA is not at all substantial. In fact, it’s a Systematic Review of other existing and previously conducted research (Oral vitamin B12 versus intramuscular vitamin B12 for vitamin B12 deficiency: a systematic review of randomised controlled trials – C.C. Butler et al.)
This paper was published ten years ago and revolves around the fact that patients with Pernicious Anaemia should be able to ‘passively absorb’ some B12 through their stomach – around 1%. Now, we have to do some arithmetic; the daily requirement of B12 is around 2.5 mcg per day. If the patient is given a 1mg tablet of B12 and absorbs 1% of it then he or she will be absorbing around 10mcg of the vitamin. And that 10mcg is four times the daily requirement. So – that’s the evidence that will be put forward to replace injections with tablets. But I’m not going to just sit here and let that happen. The fact is that when tablets were introduced as therapy in other countries there simply wasn’t any credible patient support group to put forward the views of the patients. If there is an attempt to replace injections with tablets I would hope that before this goes ahead the decision makers will contact me in order that I may put forward the evidence that this might not be such a good idea. And here’s why.
Firstly – the Review was based on research papers that were very suspect and involved groups of individuals that did not represent a wide cross section of society (the primary study was of mainly elderly males).
Secondly, what about ‘wellness’? The patients’ blood may have returned to normal but that might not mean that they would do as well on tablets as they did on injections.
Thirdly, the recommended amount of B12 replacement therapy is based on a study that began in 1947 on just seven individual patients – 7!
Some of us might need much more than 2.4mcg to feel well or correct any deficiency although it would probably be pointed out to me that even taking just 1mg of tablet will mean that the patient will be getting four times the amount he or she needs to make healthy red blood cells. And then I would point out that there seems to be something else going on regardless of the amount of B12 in the patient’s blood. Something seems to be going on at cell level. But the problem here is that the science needed to prove that some patients with Pernicious Anaemia, that is who have a problem absorbing B12 in their stomach need enormous amounts of replacement B12 is simply not there – yet. We are working with researchers to address this problem but it is still early days yet. Perhaps they will postpone any decision until after the research programmes have reported their findings.
There are other arguments I can make.
That figure of 1% being ‘passively absorbed’ is just a little too convenient for my liking. And anyway the authors of the Cochrane Review state that the patient ‘should’ absorb the 1% passively – ‘should’, not ‘will’.
Then there’s other evidence such as where tablets have been introduced to treat patients with Pernicious Anaemia doctors still keep on prescribing the injections and anyway, patients are easily able to purchase injectable B12 from other sources and treat themselves. The British Medicine’s Act that stated that medicines that are injected are available only on prescription was passed in a world that was very different from today; a world without easy access to injections in pharmacies across the world or from internet sources. If my doctor stopped my injections and told me to take oral tablets I would simply carry on self-injecting and I suspect a great many other patients would do so too. And there’s one final piece of information in my arsenal – the recent Guidelines on treating Cobalamin states that injections remain the most reliable method of treatment and that patients would prefer them as they are tried and tested.
So what’s the answer to all of this. Well, as I’ve said in my books, the Pernicious Anaemia Society has one immediate aim – to get the way in which the disease is diagnosed and treated thoroughly reviewed by someone who knows what they are doing. The question of Treatment remains the most serious problem for members. The current treatment in the UK of an injection every three months causes enormous problems for members. Simply telling patients to take tablets in the hope that they will absorb some of the B12 is based on dubious research and will force patients to by-pass their doctor. But any decision to replace injections with tablets would be something more if the decision was to be taken without consulting the Pernicious Anaemia Society – it would be arrogant and callous.
So what do we want? That’s an easy one to answer. As far as the PA Society is concerned we want patients who are newly diagnosed to be offered a choice of treatment based on the patient’s individual needs. And to do that all of the other delivery methods that could be used need to be thoroughly evaluated, not only as to their effectiveness in correcting the patient’s B12 Deficiency, but also in how the patient responds to particular delivery methods. Whilst some patients would prefer injections to skin patches or nasal sprays to sub-lingual tablets or sprays others might, and this already happens in a few cases, they might prefer daily oral tablets; but please, give us a choice of a tried and tested treatment method and not just replace our preferred method of treatment with another unpopular method.
Pernicious Anaemia was first treated using oral delivery of raw or lightly cooked offal – we don’t want to go back to that oral route surely?