ANALGESICS AND CORTICOSTEROIDS IN RHEUMATOID ARTHRITIS
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1276 The surprise which Dr. Aber and his colleagues evi- dently felt at finding a low PC02 in the presence of a severe non-respiratory extracellular alkalosis will surely be widely shared. Is it possible that potassium depletion alters the buffer properties of whole blood in some manner which invalidates the Astrup method of measuring its Pc02? It would be interesting to know if they had the opportunity to confirm the measurements by another method. In any event, their further observations will be eagerly awaited. A. POLAK. ANALGESICS AND CORTICOSTEROIDS IN RHEUMATOID ARTHRITIS MARY L. SNOWDEN. SIR,-In 1955 the joint committee on clinical trials of the Medical Research Council and the Nuffield Founda- tion compared the relative efficacy of analgesics (mainly aspirin) and corticosteroids in rheumatoid arthritis. The results of the first three years were published in 1959,1 and, as one would expect, clinical evidence and statistical analysis were presented to support each cautious conclu- sion. If the results of such a carefully controlled investi- gation are not meaningful, we may as well give up, since it is unlikely that any more exhaustive trial is either prac- ticable or economically feasible. These conclusions are denied, however, in the October issue of Prescribers’ journal. 2 There are a number of examples of this, but I will give just four: (1) M.R.C.-" In the group of patients treated with analgesics the frequency of radiological signs of erosive joint disease in the hands and feet increased significantly over the two years whereas there was no significant change in the group treated with prednisolone." .P.y.ň" Drugs ... which have no lasting effect on the progress of the disease, such as analgesics and corticosteroids." (2) M.R.C.-" The incidence of defined side effects of therapy ... were mainly of a minor character and require no comment." P.J.-" Prolonged administration, even in moderate dosage, is attended by the risk of serious side effects." (3) M.R.C.-" The patients treated with prednisolone showed an early significant improvement... and this improve- ment, though less, was still present to a significant extent, the end of two years." P.J.-" Aspirin is still the most effective and safest drug for long term administration." (4) M.R.C. (discussion).-" Dr. Duthie thought that, if the progress of erosions could be arrested, it was surely better to use prednisolone in early mild cases than in late severe ones." P.J.-" It cannot be emphasised too strongly that only when all other measures have failed ... should the use of steroids be considered." and " Steroids should rarely be used." Perhaps some new evidence has been published but a search of the literature does not show this. On the con- trary, only recently, Dr. H. F. West 3 put forward an intriguing theory on the mode of action of the cortico- steroids, in the course of which he stated: "Neither phenylbutazone nor salicylates, nor any other antirheu- matic substance has been shown to affect the course of the disease (rheumatoid arthritis) favourably in the way that prednisolone does." One cannot reconcile this with warnings that steroids are only suitable as a last measure, and that they are " drugs which have no lasting effect on the progress of the disease ". Doctors are being subjected to an increasing amount of official badgering, and the mailed fist can be seen more and more clearly through the now threadbare velvet glove. 1. Ann. rheum. Dis. 1959, 18, 173. 2. Duthie, J. J. R. Prescribers’ J. 1962, 2, 69. 3. Lancet, Sept. 22, 1962, p. 590. It must be the patient who suffers from this policy. The onslaught of continuous economically biased propaganda will result in the doctor’s therapeutic ability and judgment suffering the same fate as his patient’s joints-namely, progressive erosion, deformity, and immobility, until the process finally burns itself out in an era of therapeutic nihilism. Ifield, Sussex. MARY L. SNOWDEN. *** We showed Dr. Snowden’s letter to Dr. Duthie, whose reply follows.-ED. L. SIR,-Dr. Snowden quotes certain conclusions reached in a report published in 1959 by the clinical trials com- mittee of the Medical Research Council and the Nuffield Foundation. The duration of the trial comparing pred- nisolone with aspirin or other analgesics at this time was two years, not three. Dr. Snowden states that a search of the literature has revealed no new evidence as to the value or otherwise of corticosteroids. May I draw her attention to a further report published by the same committee in 1960, in which the results of this trial at the end of three years were reported ? This states: " The suppression of articular erosion obtained with pred- nisolone during the earlier part of the trial, when a higher dose was given, was less evident during the third year, when the mean dose was between 10 and 10.5 mg. daily, since at this lower dose there was roughly equal deterioration in the films of hands and feet in both treatment groups, and it may be that the striking advantage to prednisolone as compared with analgesics described in the first report of this trial was largely due to the profound suppressive effects of the higher dosage used in the first year, which unfortunately proved to be unacceptable because of serious side-effects such as psychosis and bleeding peptic ulceration." I suggest that Dr. Snowden read this report in full. I believe my statement that the corticosteroids, when used in safe doses, are drugs which have no lasting effect on the progress of the disease is substantially correct. I am not clear what Dr. Snowden means by " the onslaught of continuous economically biased propaganda " in connection with my article, but I can assure her that I have no financial interest in the sale of aspirin. J. J. R. DUTHIE. Northern General Hospital, Edinburgh. THE RHEUMATOID-ARTHRITIS TEST IN NON-RHEUMATOID CONDITIONS SiRjňThe rheumatoid-arthritis test is performed by mixing a suspension of latex particles, previously coated with gamma-globulin, and the patient’s serum, diluted with glycine buffer, on a glass slide. Agglutination of the latex particles within sixty seconds is regarded as a positive result, and such a result is obtained with a large percentage of sera of patients with rheumatoid arthritis. Such agglutination of gamma-globulin-coated particles or red cells is the basis of a number of tests for rheumatoid- arthritis and it is probable that all these reactions are due to a related property of the serum of patients with this condition. Glynn et al. suggest that this " rheumatoid factor " is an antibody to non-specific groupings of gamma- globulin. When testing the sera of " healthy " individuals 4% of false " positives are found. The makers suggest that even these results may in fact be due to a predisposition to the disease or to the presence of the disease in a very early form.3 1. Ann. rheum. Dis. 1960, 19, 331. 2. Glynn, L. E., Holborow, E. J., Johnson, G. D. Proc. R. Soc. Med. 1957, 50, 469. 3. Baxter Laboratories technical information bulletin, no. 4.
Transcript of ANALGESICS AND CORTICOSTEROIDS IN RHEUMATOID ARTHRITIS
1276
The surprise which Dr. Aber and his colleagues evi-dently felt at finding a low PC02 in the presence of asevere non-respiratory extracellular alkalosis will surelybe widely shared. Is it possible that potassium depletionalters the buffer properties of whole blood in some mannerwhich invalidates the Astrup method of measuring its
Pc02? It would be interesting to know if they had theopportunity to confirm the measurements by anothermethod. In any event, their further observations will be
eagerly awaited.A. POLAK.
ANALGESICS AND CORTICOSTEROIDS
IN RHEUMATOID ARTHRITIS
MARY L. SNOWDEN.
SIR,-In 1955 the joint committee on clinical trials ofthe Medical Research Council and the Nuffield Founda-tion compared the relative efficacy of analgesics (mainlyaspirin) and corticosteroids in rheumatoid arthritis. Theresults of the first three years were published in 1959,1and, as one would expect, clinical evidence and statisticalanalysis were presented to support each cautious conclu-sion. If the results of such a carefully controlled investi-gation are not meaningful, we may as well give up, since itis unlikely that any more exhaustive trial is either prac-ticable or economically feasible.These conclusions are denied, however, in the October
issue of Prescribers’ journal. 2 There are a number of
examples of this, but I will give just four:(1) M.R.C.-" In the group of patients treated with
analgesics the frequency of radiological signs of erosive jointdisease in the hands and feet increased significantly over thetwo years whereas there was no significant change in the grouptreated with prednisolone." .P.y.ň" Drugs ... which haveno lasting effect on the progress of the disease, such as
analgesics and corticosteroids."(2) M.R.C.-" The incidence of defined side effects of
therapy ... were mainly of a minor character and require nocomment." P.J.-" Prolonged administration, even inmoderate dosage, is attended by the risk of serious side effects."
(3) M.R.C.-" The patients treated with prednisoloneshowed an early significant improvement... and this improve-ment, though less, was still present to a significant extent,the end of two years." P.J.-" Aspirin is still the most effectiveand safest drug for long term administration."
(4) M.R.C. (discussion).-" Dr. Duthie thought that, if theprogress of erosions could be arrested, it was surely better touse prednisolone in early mild cases than in late severe ones."P.J.-" It cannot be emphasised too strongly that only whenall other measures have failed ... should the use of steroidsbe considered." and " Steroids should rarely be used."
Perhaps some new evidence has been published but asearch of the literature does not show this. On the con-
trary, only recently, Dr. H. F. West 3 put forward anintriguing theory on the mode of action of the cortico-steroids, in the course of which he stated: "Neither
phenylbutazone nor salicylates, nor any other antirheu-matic substance has been shown to affect the course of thedisease (rheumatoid arthritis) favourably in the way thatprednisolone does."One cannot reconcile this with warnings that steroids
are only suitable as a last measure, and that they are" drugs which have no lasting effect on the progress ofthe disease ".
Doctors are being subjected to an increasing amount ofofficial badgering, and the mailed fist can be seen more andmore clearly through the now threadbare velvet glove.
1. Ann. rheum. Dis. 1959, 18, 173.2. Duthie, J. J. R. Prescribers’ J. 1962, 2, 69.3. Lancet, Sept. 22, 1962, p. 590.
It must be the patient who suffers from this policy. Theonslaught of continuous economically biased propagandawill result in the doctor’s therapeutic ability and judgmentsuffering the same fate as his patient’s joints-namely,progressive erosion, deformity, and immobility, until theprocess finally burns itself out in an era of therapeuticnihilism.
Ifield, Sussex. MARY L. SNOWDEN.
*** We showed Dr. Snowden’s letter to Dr. Duthie,whose reply follows.-ED. L.
SIR,-Dr. Snowden quotes certain conclusions reachedin a report published in 1959 by the clinical trials com-mittee of the Medical Research Council and the NuffieldFoundation. The duration of the trial comparing pred-nisolone with aspirin or other analgesics at this time wastwo years, not three. Dr. Snowden states that a search ofthe literature has revealed no new evidence as to the valueor otherwise of corticosteroids. May I draw her attentionto a further report published by the same committee in1960, in which the results of this trial at the end of threeyears were reported ? This states:
" The suppression of articular erosion obtained with pred-nisolone during the earlier part of the trial, when a higherdose was given, was less evident during the third year, whenthe mean dose was between 10 and 10.5 mg. daily, since atthis lower dose there was roughly equal deterioration in thefilms of hands and feet in both treatment groups, and it maybe that the striking advantage to prednisolone as comparedwith analgesics described in the first report of this trial waslargely due to the profound suppressive effects of the higherdosage used in the first year, which unfortunately proved tobe unacceptable because of serious side-effects such as psychosisand bleeding peptic ulceration."
I suggest that Dr. Snowden read this report in full. I believe
my statement that the corticosteroids, when used in safe doses,are drugs which have no lasting effect on the progress of thedisease is substantially correct.
I am not clear what Dr. Snowden means by " the onslaughtof continuous economically biased propaganda " in connectionwith my article, but I can assure her that I have no financialinterest in the sale of aspirin.
J. J. R. DUTHIE.Northern General Hospital,
Edinburgh.
THE RHEUMATOID-ARTHRITIS TEST IN
NON-RHEUMATOID CONDITIONS
SiRjňThe rheumatoid-arthritis test is performed bymixing a suspension of latex particles, previously coatedwith gamma-globulin, and the patient’s serum, dilutedwith glycine buffer, on a glass slide. Agglutination of thelatex particles within sixty seconds is regarded as a positiveresult, and such a result is obtained with a large percentageof sera of patients with rheumatoid arthritis.Such agglutination of gamma-globulin-coated particles
or red cells is the basis of a number of tests for rheumatoid-arthritis and it is probable that all these reactions are dueto a related property of the serum of patients with thiscondition. Glynn et al. suggest that this " rheumatoidfactor " is an antibody to non-specific groupings of gamma-globulin.When testing the sera of " healthy " individuals 4% of
false " positives are found. The makers suggest that eventhese results may in fact be due to a predisposition to thedisease or to the presence of the disease in a very early form.31. Ann. rheum. Dis. 1960, 19, 331.2. Glynn, L. E., Holborow, E. J., Johnson, G. D. Proc. R. Soc. Med.
1957, 50, 469.3. Baxter Laboratories technical information bulletin, no. 4.
