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In reply to: Arthritis cure: the facts behind the hype
I think it may be of value for me to clarify a few points in relation
to
the recent press coverage of our novel treatment for rheumatoid arthritis.
The scientific background, and the promising outcome of the
treatment, were
presented to an audience of over 1,000 rheumatologists at the European
League Against Rheumatism Annual Meeting in Glasgow in 1999. The detailed
protocol and results were presented to the Annual General Meeting of the
British Society of Rheumatology in April. In this context it is a little
surprising that any British rheumatologist should "not have a clue what it
was all about."
Of 500 letters and emails received at UCL, none have indicated an
adverse
effect on patients. Those that express a view are thankful to be informed
and realise the research is preliminary. I have tried my best to answer
all
of them. If any person with rheumatoid arthritis is upset by this episode
I
offer them my deepest and sincerest apology. I am more concerned that
others may be advising patients without having informed themselves of the
true situation.
The word cure, in the form "possible cure" has been on my web site
for two
years. Our treatment was specifically designed to be a cure, in contrast
to
all treatments for arthritis other than high dose chemotherapy and stem
cell rescue. Robert Matthews used the word appropriately. Others may not
have. We have not claimed a cure, merely that we had set out to cure and
that results so far are as good as we had hoped on the first attempt and
extremely useful in the short term.
The new drug is a monoclonal antibody called rituximab. With
prednisolone
and cyclophosphamide, it removes, rather than antagonises, B cells.
Cyclophosphamide and steroids do have side effects but evidence from
treatment of over 50,000 cases indicates that, in the doses used in this
protocol, these drugs may well be as safe as the anti-inflammatory tablets
most arthritics take life long and very probably safer than continuous
treatment with steroids, methotrexate or azathioprine. The protocol I
would
currently favour is Day 1-4 and 15-18: prednisolone 60mg by mouth, Day 2
and 16: rituximab 800mg IV, Day 3 and 17: cyclophosphamide 10mg/Kg IV with
appropriate antiemetic, gastroprotective and anti-pyretic cover, involving
two overnight hospital stays. In the original protocol approximately 2.1gm
of rituximab was given in four doses. The results of the treatment in the
first five patients were so clear cut that we could say with 95%
confidence
that further similar patients treated in this way would have a chance of
major improvement comparable to that reported with any existing drug,
without requiring regular medication for, on average, one year. The second
five patients confirmed this. The cost of the drugs will depend on the
dose
but may be £2000-3500. Hoffman la Roche are running a trial with centres
planned in England, continental Europe, Canada and Australia. Referring
physicians can obtain information on UK centres from UCL. Although the
drugs have been available for some time I would not recommend
indiscriminate off-label use for three reasons. 1. We need to be sure
there
are no disease-specific adverse reactions. 2. We need to identify the best
drug combination. 3. Although we have not seen significant problems we
need
to learn the best way to manage the relapses that can occur when B cells
return.
Whether this development has been "hyped", time will tell. What is
clear is
that physicians who had been unaware of this approach despite several
years
of publication from several centres, and who might otherwise have gone
shopping on Wednesday afternoon in Philadelphia, are now informed.
Scientists from four continents have asked for information and expressed
interest in setting up trials. As a direct result of the press coverage,
research will be significantly accelerated and many more patients will
have
the opportunity to be involved. In short, Robert Matthews caught the
establishment napping.
Dr Cambridge's description of this treatment as the result of fifteen
years
hard work with little funding is a reasonable understatement. We currently
have no funding at all to analyse the hundreds of samples from treated
patients which might tell us why this treatment is working and how we
might
get it to work better.
Professor Jonathan CW Edwards MD FRCP
UCL Centre for Rheumatology,
Arthur Stanley House
40-50, Tottenham St.
London W1P 9PG
In reply to: Arthritis cure: the facts behind the hype
Dear Sir,
In reply to: Arthritis cure: the facts behind the hype
I think it may be of value for me to clarify a few points in relation
to
the recent press coverage of our novel treatment for rheumatoid arthritis.
The scientific background, and the promising outcome of the
treatment, were
presented to an audience of over 1,000 rheumatologists at the European
League Against Rheumatism Annual Meeting in Glasgow in 1999. The detailed
protocol and results were presented to the Annual General Meeting of the
British Society of Rheumatology in April. In this context it is a little
surprising that any British rheumatologist should "not have a clue what it
was all about."
Of 500 letters and emails received at UCL, none have indicated an
adverse
effect on patients. Those that express a view are thankful to be informed
and realise the research is preliminary. I have tried my best to answer
all
of them. If any person with rheumatoid arthritis is upset by this episode
I
offer them my deepest and sincerest apology. I am more concerned that
others may be advising patients without having informed themselves of the
true situation.
The word cure, in the form "possible cure" has been on my web site
for two
years. Our treatment was specifically designed to be a cure, in contrast
to
all treatments for arthritis other than high dose chemotherapy and stem
cell rescue. Robert Matthews used the word appropriately. Others may not
have. We have not claimed a cure, merely that we had set out to cure and
that results so far are as good as we had hoped on the first attempt and
extremely useful in the short term.
The new drug is a monoclonal antibody called rituximab. With
prednisolone
and cyclophosphamide, it removes, rather than antagonises, B cells.
Cyclophosphamide and steroids do have side effects but evidence from
treatment of over 50,000 cases indicates that, in the doses used in this
protocol, these drugs may well be as safe as the anti-inflammatory tablets
most arthritics take life long and very probably safer than continuous
treatment with steroids, methotrexate or azathioprine. The protocol I
would
currently favour is Day 1-4 and 15-18: prednisolone 60mg by mouth, Day 2
and 16: rituximab 800mg IV, Day 3 and 17: cyclophosphamide 10mg/Kg IV with
appropriate antiemetic, gastroprotective and anti-pyretic cover, involving
two overnight hospital stays. In the original protocol approximately 2.1gm
of rituximab was given in four doses. The results of the treatment in the
first five patients were so clear cut that we could say with 95%
confidence
that further similar patients treated in this way would have a chance of
major improvement comparable to that reported with any existing drug,
without requiring regular medication for, on average, one year. The second
five patients confirmed this. The cost of the drugs will depend on the
dose
but may be £2000-3500. Hoffman la Roche are running a trial with centres
planned in England, continental Europe, Canada and Australia. Referring
physicians can obtain information on UK centres from UCL. Although the
drugs have been available for some time I would not recommend
indiscriminate off-label use for three reasons. 1. We need to be sure
there
are no disease-specific adverse reactions. 2. We need to identify the best
drug combination. 3. Although we have not seen significant problems we
need
to learn the best way to manage the relapses that can occur when B cells
return.
Whether this development has been "hyped", time will tell. What is
clear is
that physicians who had been unaware of this approach despite several
years
of publication from several centres, and who might otherwise have gone
shopping on Wednesday afternoon in Philadelphia, are now informed.
Scientists from four continents have asked for information and expressed
interest in setting up trials. As a direct result of the press coverage,
research will be significantly accelerated and many more patients will
have
the opportunity to be involved. In short, Robert Matthews caught the
establishment napping.
Dr Cambridge's description of this treatment as the result of fifteen
years
hard work with little funding is a reasonable understatement. We currently
have no funding at all to analyse the hundreds of samples from treated
patients which might tell us why this treatment is working and how we
might
get it to work better.
Professor Jonathan CW Edwards MD FRCP
UCL Centre for Rheumatology,
Arthur Stanley House
40-50, Tottenham St.
London W1P 9PG
Competing interests: No competing interests