Examination of Witnesses (Questions 180-199)
PROFESSOR STEPHEN
DURHAM, PROFESSOR
PETER BARNES,
PROFESSOR ANDREW
WARDLAW AND
PROFESSOR ANTHONY
FREW
18 DECEMBER 2006
Q180 Baroness Perry of Southwark:
In general do you think that the treatments that are available
for allergic diseases like asthma, hay fever and anaphylaxis are
clear and easy for patients to understand and administer correctly?
Professor Barnes: I would say that the current
therapies for rhinitis and asthma are very effective for the majority
of patients and relatively simple. The mainstay therapy for asthma
is inhaled steroids, plus in many cases a long-acting beta agonist
and these are highly effective forms of treatment for asthma.
There are also effective treatments for rhinitis. Treatments for
eczema are less effective, but there are patients where these
simple treatments are not very effective and these patients often
need specialist attention. Traditionally we would expect patients
with difficult asthma to come to pulmonologists and patients with
difficult eczema to be referred to dermatologists.
Professor Frew: One of the issues here is that
for a lot of patients who have anaphylaxis and food allergies
it is about appropriate avoidance of triggers and also provision
of first aid therapy. There is not in that case a treatment that
you give on a routine basis. The main issue is about access to
a correct diagnosis which then leads through to correct advice,
so some of it is about getting the history and then coupling that
to the advice that is available and using the existing medications
that are available.
Q181 Baroness Perry of Southwark: Do
you think there are any ways in which allergy treatments could
be improved to make them safer, for example, to be used by children
in school during each day?
Professor Frew: As Professor Barnes has said,
the existing treatments for asthma and rhinitis are safe and easy
to use. There is not really a problem with those. There is a limit
on how effective they are, so there is room for further improvement.
In relation to food allergy, where what you are trying to do is
avoid ingestion but if they do have an accident you may have to
administer injectable adrenalin, clearly what we would like to
do is move forward to a situation where we can treat this and
get rid of the condition rather than simply being there as a safety
net in case somebody eats something they should not.
Q182 Chairman: Could you explain
what the place is for anti-IgE therapy, whether it is only in
severe disease or whether it could be used earlier on and should
be used earlier on?
Professor Barnes: One of the problems of anti-IgE
therapy is its enormous expense. It costs something like £10,000
a year to treat some patients with higher levels of IgE, so it
could only really be considered for very severe asthma patients,
but there is no doubt that some patients respond very well who
have not been controlled by conventional therapy, so we would
really only consider patients not controlled on maximum doses
of inhaled therapy for asthma and, in particular, patients who
need to have steroid tablets that have a lot of side effects,
as potentially suitable for this therapy. If it were much cheaper
it then might be applicable to a broader population of people
with allergy.
Q183 Viscount Simon: Do all people
with allergy have an altered IgE?
Professor Wardlaw: That is a very profound question.
It depends how you define allergy. Some people define it quite
narrowly as only people who have got IgE disease involving abnormal
amounts of IgE. It can be defined more widely as conditions which
have many manifestations that look like allergy or that I would
regard as allergic but when that particular mechanism is not involved.
I would say 75 per cent of allergy at least is IgE mediated. Going
back to Professor Barnes, it is an excellent and fascinating treatment
which has a place in a very specialist setting in a relatively
small number of severe asthmatics, but could be of considerable
use. It is frustrating at the moment, certainly in my experience
and I suspect others', that the purchasers are not willing to
purchase it very readily, which is a problem for us.
Q184 Lord Rea: I wondered if you
could see the cost of anti-IgE therapy coming down. Is it a question
of patents or is it something else that makes it so expensive?
Professor Frew: It really is a question of production
costs and this links a little bit to volume of sales. There are
certainly lots of patients that we see, who might benefit but
who will not get it at the current price this is not a question
of appropriateness; this is a question of price. In terms of the
future, I do not think the patents are the limiting factor. I
think it is genuinely expensive to produce and it is difficult
to see it ever coming down to the level of cost that we have for
the standard inhaler treatments for asthma.
Q185 Lord Soulsby of Swaffham Prior:
Is it a monoclonal antibody?
Professor Frew: It is a monoclonal antibody
which is given in quite large quantities quite frequently, and
it is the combination of the frequency of administration, the
production costs and associated hospital costs that make the treatment
an expensive option.
Q186 Lord Taverne: We have already
had your comments that we should look more at anti-IgE therapy
and immunotherapy, and that there are shortcomings in the simple
therapies for rhinitis and asthma, but in what other respects
do you think the Government's policies on the prevention and treatment
of allergy are adequate or inadequate and, if inadequate, what
else should we be doing?
Professor Wardlaw: The BSACI have had a lobbying
campaign for a number of years to try and persuade the Department
of Health that what is needed is better allergy provision throughout
the spectrum of care in primary care and through specialist care,
and that what we need is a cadre of specialists who can lead the
management and treatment of allergies at a national level. Of
course, you are aware that there has been a big review by the
Department of Health and generally we are rather disappointed
by the outcome of that review. They recognised, I think, that
there was a major problem and that the NHS had not kept up with
that problem in terms of service provision, but they came up with
no real solutions to that problem and did tend to pass the buck
in my view to the PCTs for whom it is not a priority and who will
not pick up that buck. At the moment we feel that the Department
of Health does not have adequate policies to address the allergy
epidemic.
Professor Durham: If I may emphasise what Professor
Wardlaw has said, there was a report from the Royal College of
Physicians four years ago that was endorsed not only by the college
but also the specialists within the college to encourage an improvement
in allergy services in the UK. This went on to the Select Committee
report which reported two years ago. The Government saw fit at
that stage to set up its own review, which was something of a
surprise to us, but then it was a year later that we had the recommendations
and, as Professor Wardlaw says, the problem is that they fully
acknowledge that there is a problem, that there is a modern epidemic,
that there is a lack of training and that there is a lack of resources,
but provided no solutions and in my view really ignored the recommendations
of the Select Committee. The only positive things that came out
for allergy sufferers, who we should be focusing on, was the need
for NICE to develop guidelines, as we have already discussed,
and the fact that we need more trainees in allergy. This was openly
acknowledged in the report but the only limp suggestion was that
we contact the regional deaneries to see how this would come about
with no central funding. We have gone through this consultative
process, certainly within the North West Tees Deanery, and there
is no money to encourage more trainees. That is my concern with
the Department of Health review. I think it is a very inadequate
response to a major problem that has already gone through four
years of consultation.
Q187 Lord Taverne: What you say is
obviously very important and disturbing but what about the advice
that government gives to sufferers? We have heard that with the
current state of knowledge and the aetiology of IgE it is sometimes
more truthful to give advice on what is not working. With respect
to my colleague, should part of government advice perhaps be to
avoid alternative medicine practitioners who do not diagnose and
thereby often may do considerable damage, or at least treat them
with greater suspicion?
Professor Frew: It is fair to say that the knowledge
base is limited at the moment. We do not know precisely what to
do to advise, for example, pregnant or prospective mothers about
how to reduce the chances of their children becoming allergic.
We do know some things we can advise them. If they ask us about
particular courses of action, we can give them the evidence that
is available on whether, for example, avoiding peanuts in pregnancy
might be helpful or not, but we are still short of accurate information
and, of course, it is a difficult thing to do because you are
making decisions at a very early stage in life with children who
are healthy in order to try to prevent something happening some
years downstream. These are long, complex studies which are usually
beyond individual institutions or individual funding bodies to
put money towards, and I think there is still a need, and it will
be covered in the next session, for further research in this area
to improve the advice that we can offer people to prevent it.
In terms of advice on treatment, we are much closer to being able
to say, "These are the things that you can and should do,
and these are things that can and should be available widely across
the country but currently are not available due to inequalities
in provision".
Q188 Lord Taverne: What about advice
about what you should not do, again, a particular question about
alternative medicine because I gather that 90 per cent of sufferers
do go to alternative practitioners?
Professor Frew: I believe there are several
reasons why people go to alternative therapists. Some of them
are because of dissatisfaction with the availability of conventional
services, some of them relate to popular views of how the body
works, which differ somewhat from the way doctors see the world.
Within reason, it is a free country, so people should be given
balanced advice and information on alternative medicine. If they
then wish to go and spend their money on these things then I do
not have a problem with that.
Q189 Lord Colwyn: My flier here from
Asthma UK says that 5.2 million people have asthma, they lose
12.7 million working days a year and the annual cost to the economy
is £2.3 billion. We also read that patients actually cannot
even afford the treatment, so no wonder they start going to other
practitioners. Do you agree with that?
Professor Durham: I just want to endorse the
reasoning that there is such a broad practice of allergy advice
available now on the street and it is an attempt to meet the unmet
need and people are forced on to the high street.
Q190 Lord Taverne: But my question
is, should they be advised to be very careful about it because
they can do more harm than good?
Professor Durham: They may not do harm in themselves.
For example, Chinese remedies for treating eczema have been shown
in five out of 12 cases to contain topical steroids in them, so
so-called traditional remedies may not be as traditional as patients
are led to think, but I think the real issue here is diverting
patients from the care that they need. If they have acute severe
asthma they need to be managed by a pulmonologist and have access
to emergency facilities. If they have multi-system disease they
need to see a specialist allergist at a one-stop-shop that can
deal with the allergic components of all those different conditions
at one visit and that is not the sort of thing that you get on
the high street.
Q191 Lord Colwyn: There are only
14 in the UK.
Professor Barnes: I do agree with your concern
that alternative therapies are widely used to treat allergic diseases
and, of course, are promoted by the media, whereas often conventional
therapies are criticised by the media. The fact is that almost
all alternative therapies, at least for asthma, that have been
tested by adequate controlled trials have been shown to be completely
ineffective. I think it is our duty to try and warn people that
these treatments are not working because people pay money for
those therapies and, as Professor Durham has said, the danger
is that they may stop using conventional therapies that are effective.
I think some practitioners advise people not to take conventional
medicines which have quite a bad press, so I think it is an important
duty to warn people about the inefficacy of alternative therapies.
Professor Wardlaw: On the specific questions
about government advice, I would say that the Government should
not be funding alternative remedies that are not based on good
scientific evidence. That is where the Government's work should
be. Obviously, we are all very regulated now in our practice and
they should also be making sure that patients are not exposed
to treatments which can be harmful, and that does include, I suppose,
situations where the patients would otherwise be prevented from
taking beneficial treatments.
Lord Colwyn: If they are available.
Q192 Chairman: Could I go back very
briefly to the workforce planning because we have heard that the
Walport clinical academic trainee numbers have been increased
by, I think, 11 going into allergy training. Do you think that
is going to be adequate to address the need?
Professor Frew: I think it will help in terms
of building the academic workforce. It is not going to help in
terms of building the service workforce.
Professor Wardlaw: I think it has got no role
for allergy. The Walport scheme is not, except maybe in one or
two centres, suitable for allergy.
Q193 Lord Soulsby of Swaffham Prior:
We are dealing with immunotherapy and you have mentioned IgE
but, apart from IgE, what other immunotherapies are used?
Professor Durham: There is the treatment referred
to as allergen immunotherapy. This treatment is used quite widely
in Europe but less so in the United Kingdom. It is only indicated
in patients with IgE mediated disease and it is effective in patients
with a limited spectrum of allergies. It should be prescribed
and administered by trained people in a specialist environment.
The people who are most likely to benefit from immunotherapy are
two groups of patients. There are patients with severe hayfever
which does not respond to conventional treatment, and the second
group, in whom the treatment is life-saving, is in patients with
venom anaphylaxis from stinging insects, wasps and bees. The point
about this treatment is that it is not like prevention treatment.
There are two points I would like to make about this treatment.
First of all, in those defined circumstances it is extremely effective
and it does things that conventional medications do not do: it
induces long term remission after stopping the treatment. In children
you can actually prevent the onset of new sensitisations by treating
children earlier, and there is some evidence from randomised control
trials that you may prevent progression, for example, from rhinitis
to asthma, so there are very good reasons for prescribing this
therapy in patients who fail to respond to the usual therapies.
The drawback is that with conventional immunotherapy that is given
by injection there is a risk of inducing systemic allergic reaction,
and in the United Kingdom it is specifically contra-indicated
in patients with chronic asthma. In previous times when there
have been adverse effects they have been in patients with chronic
asthma. It does have a role. It has a limited role in patients
who fail to respond to usual therapy. In terms of research and
development, if I may just extend that answer, we know this form
of therapy is effective but if we could make it safer or develop
novel strategies for immunotherapy then it may be more broadly
available. In this context recently there has been developed a
sublingual form of immunotherapy, not by injection but taken under
the tongue, which is used for patients with severe hay fever.
This treatment has been shown to be effective and has also been
shown to be safe such that the patient is able to take this form
of therapy in their home.
Q194 Lord Soulsby of Swaffham Prior:
Why sublingual? Is there lots of tissue that can process it?
Professor Durham: I think the answer to that
question is yes. If we look at animal models using the oral route,
it is a very effective way of inducing immunological tolerance,
and this is a natural extension of that work on animals. The evidence
base has accumulated over the past 10 years that this is an effective
way of inducing tolerance to selected allergens, in particular
to grass pollen and also to tree pollen. Those are the two areas
where this has been shown to be particularly effective. If you
look at the 12 million hay fever sufferers in this country, 23
per cent of the population, 40 per cent of those would say that
they currently are dissatisfied with their therapy, and this is
work from Professor Frew's group, so I am quoting work from his
group. Probably 75 per cent of that group are not taking the treatment
appropriately or regularly, but there is a hard core of sufferers,
I would suggest between half a million and a million, who would
really benefit from the sublingual form of this treatment which
has been shown to be effective.
Q195 Lord Soulsby of Swaffham Prior:
We understand that immunotherapy is more commonly used on
the continent of Europe than in this country. Is there a reason
for that? Should there be more courses?
Professor Durham: Could I defer to Professor
Frew on that?
Professor Frew: I deal with allergy in different
parts of Europe and am very familiar with the differences in practice
there. Most of these are just historical. It is the way the services
have developed in different countries. We used to do quite a lot
of immunotherapy in this country but it was done at the primary
care level. People from the allergen manufacturer used to go around,
make the diagnosis and provide vaccines for use in general practice
surgeries. There were a number of problems with this, and indeed
between 1952 and 1986 there were about 27 fatalities associated
with immunotherapy, almost entirely patients with severe asthma,
as Professor Durham said. The CSM, the Committee on the Safety
of Medicines, then put some restrictions on immunotherapy and
said that it could only be done in places where they were familiar
with its use and had resuscitation facilities available. Ironically,
if that happened today, general practices have those facilities
available to do it but in 1986 they did not and so effectively
it stopped the practice of immunotherapy at a devolved level in
the community. We were then thrown back on to the very small number
of centres that were doing immunotherapy and it meant that for
logistic reasons patients have not been able to access this. For
example, in Southampton and in Bournemouth, where I was working
until last year, we had very active clinics doing desensitisation
but we also saw many patients who would come from some distance
away to see us, but who were simply not able to make the repeated
journeys to come and get the treatments done and would have to
decide that they could not go through with this. The other issue
is again about the organisation of the NHS, that because we are
organised around organ-based specialities, many of these patients,
when they were sent up from the general practice, went to see
somebody who was not very allergy oriented and who thought that
it was not appropriate for them to have immunotherapy. The third
point is that when we have gone back to the MHRA, as it is now,
to try to get product licences for some of the vaccines, the MHRA
have taken a very stern line with this. It has been much more
strict in terms of the regulation than other parts of Europe,
so they have derogated from the mutual recognition process which
would normally allow for these vaccines to be available in this
country and told the companies concerned that they may be available
in Sweden and Denmark and other countries but they are not going
to allow them to go through on a mutual recognition process, which
is the normal way by which these vaccines would have been made
available in this country. We are not entirely clear why they
are quite so concerned about this but there has been difficulty
in getting allergist opinion, if you will, to speak to the CSM
and the MHRA because there are not many allergists around, there
is no allergist on the committee, and therefore sometimes the
opinions that are expressed there are rather anti-immunotherapy.
Q196 Lord Soulsby of Swaffham Prior:
In view of the success of the sublingual approach to immunotherapy
what is the potential for treating food allergies by sublingual
application with selected items of food?
Professor Durham: If I may, my Lord Chairman,
I will ask Professor Frew to address the food allergy issue. In
relation to hay fever, I think we should be cautious. We have
phase three trials now that show that sublinguals are effective
and we have good safety data from 2,000 patients. In terms of
its fragmented distribution I think we would want to see good
safety data from 20,000 patients. I think there has to be a cautious
introduction through specialist centres. I would be concerned
if this form of therapy was prescribed ad hoc at this stage by
general practitioners, for example. I think to inject enthusiasm
but also an element of caution to the sublingual route is important.
Q197 Lord Colwyn: The sublingual
route is not new. It has been used for thousands of years. It
is used when someone is having a heart attack. The first thing
you do is put aspirin in sublingually.
Professor Frew: Absolutely, and many drugs are
absorbed very efficiently from the mucosa in the mouth. It has
the advantage that it gets into the system quickly and bypasses
the liver. If you give a drug via the gut, it takes time to get
there and is metabolised as it goes through the liver, so putting
something under the tongue is a very efficient way of getting
some drugs into the system. In the case of sublingual immunotherapy,
what you are hoping to do is to present the allergen to the immune
system by getting it taken up by specialised cells in the lining
of the mouth. In terms of food allergy, there is a lot of interest
in developing vaccines, for example, to peanut allergy. There
is some very good work being done on peanut allergy in the States,
mostly in terms of injection vaccines, but, if we could get a
sublingual vaccine for it that would be easier for patients to
administer. The problem I see at the moment is that with peanuts
you are dealing with anaphylaxis and so the risk of precipitating
the condition you are treating is higher than it is with hay fever,
where it does not matter if you make somebody's nose run but it
does matter if you give them anaphylaxis. Many of the patients
with peanut allergy react to extremely low levels of peanut. Just
touching peanut to the lip can precipitate an anaphylactic reaction.
The stakes are higher in that situation in terms of the risk of
causing side effects, but also the benefit to patients and particularly
children would be enormous.
Q198 Lord Taverne: Is the sublingual
method of treating it different from the pill that was recently
referred to?
Professor Durham: No. That is the sublingual
route. It can be given either in the form of drops or as fast-dissolving
tablets.
Q199 Lord Taverne: The second question
is that you mentioned that there were risks associated with injection,
but in the paper which you submitted to us it did say that injection
is highly effective and safe when performed by trained persons.
Professor Durham: Yes.
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