CONTROVERSY IN THE TREATMENT OF RHEUMATOID ARTHRITIS

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Regulations, it should bring this evidence to the notice of theDHSS.The greatest responsibility, however, falls on the medical

profession. For public confidence to be restored, we mustaccept two basic principles. First, we must appreciate that inour individual relationships with the industry we mustneither be compromised, nor be seen to be compromised.Secondly, we must reject the self-deception that we can acceptthe industry’s blandishments, yet simultaneously reject thepromotional messages. We should also take specificmeasures.

1. Individual members of the profession must be preparedto make a formal complaint to the ABPI when they believethat a breach of its code has occurred.

2. Doctors must cease accepting hospitality which formspart of drug promotion. It is time we paid for our own drink,food, and winter breaks.

3. Doctors must stop making demands on the industry forcontributions to their travelling expenses. Requests to

individual companies, particularly from senior clinical

academics, for funds to attend conferences in far-away placesare a major embarrassment to the industry.

4. Doctors working outside the industry must abstain frompublicly endorsing a company’s products in the media.

Examples of this practice, so vividly documented byMedawar,1 I should become ancient (rather than

contemporary) history.Unfortunately, I do not believe that voluntary action by the

profession is sufficient. The new GMC must also take firmsteps to restore the profession’s credibility with the public. Ifsuch measures are not forthcoming, public confidence in theprofession’s mechanism for self-regulation will be seriouslyjeopardised.

1. The GMC should reaffirm-its advice to doctors" thatthey should declare financial details of industry-sponsoredresearch to local ethics committees.

2. The council should require doctors to declare anypersonal payments they receive from pharmaceuticalcompanies (eg, consultancy payments) to their employing (orcontractual) authority (eg, Health Authority, FamilyPractitioner Committee).

3. Deliberate public endorsement of a company’s productby a doctor working outside the industry should be regardedas professional misconduct.Action must also be taken by those entrusted with the

responsibility for organising postgraduate education, and bycentral Government. While I would not wish to stop industrysponsorship of meetings in postgraduate centres, deans andtutors should ensure that the programme really has beendrawn up independently of the company. Furthermore, stepsshould be taken to reduce expenditure on drug promotion, forreduction of the sums available would inevitably diminish theability of the industry to offer indirect financial incentives todoctors. Powers to do this are already available to theGovernment under the Pharmaceutical Price RegulationScheme. Although the Minister of Health has announcedmeasuresl5 which he believes will reduce the promotionalbudget by 25%, from an all-time high of 180 million in1983-84, this should only be a start: I would like to see it fallby at least two-thirds. Finally, the DHSS must act morevigorously to ensure that the law relating to drugadvertisement is upheld. If it needs strengthening theMinister of Health should be prepared to seek further powersfrom Parliament.

M. D. RAWLINS: REFERENCES

1. Medawar C. The wrong kind of medicine? London: Consumer’s Association & Hodder& Stoughton, 1984.

2. Melville A, Johnson C. Cured to death. London: Secker & Warburg, 1982.3. Mangold T. Relationship between doctors and salesmen are lurching out of control

Listener Jan 20, 1983: 2-4.4. Editorial. Opren scandal. Lancet 1983; i: 219-20.5. Rawlins MD. The role of the pharmaceutical industry in postgraduate medical

education. Br J Clin Pharmacol 1977; 4: 257-59.6. ABPI Data sheet compendium, 1984-85. London: Datapharm Publications, 1984.7. ABPI Code of Practice Committee. Some companies censored. Pharmaceut J 1984;

232: 628-29.

8. Davey P. Comparative clinical trials of antimicrobial drugs. J Antimicrob Chemother1984; 13: 204-08.

9. French TA. Commercial approach of the pharmaceutical industry. Br Med J 1983,287: 1632.

10. WHO Scientific Group. Principles for the clinical evaluation of drugs. WHO TechnRep Ser 1968; 403: para 4.5.

11. General Medical Council. Professional conduct and discipline: fitness to practiseLondon: GMC, 1983.

12. Ball JG, Snell ES. Payments to doctors and the responsibilities of ethics committees BrMed J 1983; 287: 1884.

13. Diamond AL, Robinson K. Payments to doctors and the responsibilities of ethicscommittees. Br Med J 1984; 288: 322-23.

14. Cousins J. Payment to doctors and the responsibilities of ethics committees. Br Med J1984; 288: 323.

15. Department of Health and Social Security. Revised pharmaceutical price regulationscheme: Kenneth Clarke’s statement 83/276. London: DHSS, 1983.

Debate

CONTROVERSY IN THE TREATMENT OFRHEUMATOID ARTHRITIS

ROBIN C. BUTLER DAVID H. GODDARD

Department of Rheumatology, Charing Cross Hospital, FulhamPalace Road, London W6, and Department of Rheumatology,

Westminster Hospital, Horseferry Road, London SW1

AT a recent meeting of the Heberden Society and the BritishAssociation for Rheumatology and Rehabilitation, the motion "thatremission-inducing drugs are not worth while" was debated.

Although the motion was overwhelmingly defeated, a sizeableminority voted in favour and many abstained. Remission-inducingdrugs continue to be prescribed by rheumatologists, yet their useremains highly controversial. How, and indeed whether, theyshould be used and the studies necessary to clarify their role werediscussed at a meeting of senior registrars in rheumatology and apanel of senior members of the specialty in Stratford-upon-Avon inMarch, 1984.

Gold and Penicillamine

In view of the uncertainty about the efficacy and mode of action ofthese drugs in rheumatoid arthritis (RA) it was generally agreed thatthe use of drug names was preferable to terms such as "remission-inducing" or "disease-modifying".

-

Trials have shown that gold and pefiicillamine produce animprovement in disease symptoms, erythrocyte sedimentation rate,and C-reactive protein values over 6-18 months.I-6 Evidence thatthese drugs affect long-term outcome7 or retard radiologicaldeterioration8 is scanty; indeed radiological progression may occurdespite improvement in clinical and laboratory measurements.9

9

Because few patients take these drugs for long periods,determination of their efficacy is difficult. 10, 11 Nevertheless, manyof the participants felt that treatment with gold or penicillamineprompts disease remission in some patients but that the value ofthese drugs is obscured by the comparatively poor response inothers. Genetic and immunological study of these patients wasrecommended in an attempt to define factors affecting drugresponse. For future studies it was considered vital to stratifypatients for possible markers of responsiveness and disease severitysuch as HLA-DR status and rheumatoid factor titre. There was,however, little support for further trials of single drugs. At present,one or other drug is started and an improvement in 6-12 months isanticipated; when side-effects occur, or the drug appears

279

ineffective, an alternative drug, possibly chloroquine or

sulphasalazine, is substituted. Suggestions were made that the long-term use of these drugs should be compared with gold or

penicillamine for 6 months only, or with placebo, and that newapproaches, such as drug combinations and intermittent treatmentregimens, should be tested.

Corticosteroids

Before the meeting, a questionnaire about corticosteroid

prescribing was sent by Dr M. Byron to 250 consultant

rheumatologists; 198 replies were received. Replies to the question"do you ever initiate corticosteroid therapy in uncomplicated RA?"were: 33% occasionally; 4% frequently; 51% very infrequently; and12% never. Further analysis of the experience at one centre revealeda discrepancy between the clinician’s stated opinion and his actualpractice. Such a discrepancy is well recognised in clinical decision-rnaking.12 Thus, the belief that corticosteroids should be avoided inRA is not generally practised.In early studies comparing cortisone with aspirin in RA 13,14 no

clear therapeutic advantage for cortisone was demonstrated in themedium term (ie, 3 years). However, when prednisolone wascompared with analgesics (usually aspirin or phenylbutazone) in a3-year trial, the corticosteroid group showed improvement in bothclinical features and laboratory indices of disease activity andsignificantly less radiological progression. IS Another trial suggestedthat low-dose prednisolone was unlikely to be so effective. 16 Even ifcorticosteroids are of benefit, such benefit must be weighed againsttheir side-effects.There was general agreement that two main studies of

corticosteroids are required: a study of long-term low-dose

prednisolone (ie, 7’ 5-10 mg daily) given early in the course of thedisease to test for possible disease modification, and a study ofintermittent high-dose prednisolone (ie, 100-125 mg by mouth orinjection every 4-6 weeks) to test for a fundamental effect on theevolution of the disease.

Immunosuppressive DrugsIn controlled studies cyclophosphamide,17 azathioprine, 18 and

chlorambucili9 have been shown to reduce synovitis in RA. In onestudy of cyclophosphamide, a reduction in the rate of formation oferosions was observed. 17 Methotrexate2° may also be valuable, butcontrolled data are awaited. The risk of oncogenesis is the greatestbarrier to the use of these drugs in RA. The magnitude of the riskhas yet to be quantified though these data should eventually beavailable through the EULAR registry.21Long-term trials of single drugs using conventional dosage

regimens were considered to be of limited value, and it was

suggested that different treatment strategies should be tried.z2These included: intermittent use of a single agent in high dose; useof a single agent in conventional doses in combination with gold orpenicillamine; and use of combinations of cytotoxic drugs given

‘

either as low-dose continuous or high-dose intermittent regimens.Patients with severe progressive disease who had not responded toother treatments were considered -to be most suitable for thesestudies, but the need for identifying predictive factors of

malignancy in such patients was emphasised.

Cost versus BenefitNo definite decision was reached as to whether the beneficial

effect of the drugs outweigh their cost in terms of toxicity andpatient and NHS resources. Many felt that the success of futuremanagement of RA would depend upon a new approach to

treatment in which aggressive drug regimens are used early in thecourse of the disease. For ethical reasons, such a policy will only bepermissible when patients at risk from severe and progressivedisease can be identified with accuracy. Whether such a treatment

strategy will enable clinicians to abort RA in its earliest stages is aquestion of fundamental importance that urgently requires ananswer.

All correspondence should be addressed to R. C. B.

R. C BUTLER AND D. H. GODDARD: REFERENCES

1. Research Committee ofthe Empire Rheumatism Council. Gold therapy in rheumatoidarthritis Report of a multicentre controlled trial. Ann Rheum Dis 1960; 19:95-119.

2. Research Committee of the Empire Rheumatism Council. Gold therapy in rheumatoidarthritis. Report of a multicentre controlled trial. Ann Rheum Dis 1960; 20: 315-34.

3. Sigler JW, Bluhm GB, Duncan H, Sharp JT, Ensign DC, McCrum WR. Gold salts inthe treatment of rheumatoid arthritis. A double-blind study. Ann Intern Med 1974;80: 21-26.

4. Dixon AStJ, Davies J, Dormandy TL, et al. Synthetic D(-) penicillamine inrheumatoid arthritis Double-blind study of high and low-dosage regimen. AnnRheum Dis 1975; 34: 416-21:

5 Andrews FM, Camp AV, Day AT, et al. Controlled trial of D(-) penicillamine insevere rheumatoid arthritis Lancet 1973; i. 275-80.

6. McConkey B, Davies P, Crockson RA, Crockson AP, Butler M, Constable TJ, AmosRS Effects of gold, dapsone, and predmsone on serum C-reactive protein andhaptoglobin, and the erythrocyte sedimentation rate in rheumatoid arthritis. AnnRheum Dis 1979; 38: 141-44

7. Fries JF. Towards an understanding of patient outcome measurement. Arthritis Rheum1983; 26: 697-704.

8. Iannuzzi L, Dawson N, Zein N, Kushner I. Does drug therapy slow radiographicdeterioration in rheumatoid arthritis? N Engl J Med 1983; 309: 1023-28.

9. Scott DL, Grindulis KA, Struthers GR, Coulton BL, Popert AJ, Bacon PA.Progression of radiological changes in rheumatoid arthritis. Ann Rheum Dis 1984;43: 8-17.

10. Sambrook PN, Browne CD, Champion GD, Day RO, Vallence JB, Warwick N.Terminations of treatment with gold sodium thiomalate in rheumatoid arthritis. JRheumatol 1982; 9: 932-34.

11. Day AT, Golding JR, Lee PN, Butterworth D. Penicillamine in rheumatoid disease: along-term study. Br Med J 1974; i: 180-83.

12. Kirwan JR, Chaput de Saintonge DM, Joyce CRB, Currey HLF. Clinical judgement inrheumatoid arthritis. II Judging "current disease activity" in clinical practice AnnRheum Dis 1983; 42: 648-51.

13. Joint Committee of the Medical Research Council and Nuffield Foundation. Acomparison of cortisone and aspirin in the treatment of early cases of rheumatoidarthritis. Br Med J 1955; ii: 695-700.

14. Empire Rheumatism Council. Multicentre controlled trial comparing cortisone acetateand acetyl-salicylic acid in the long-term treatment of rheumatoid arthritis. AnnRheum Dis 1957, 16: 277-89.

15. Joint Committee of the Medical Research Council and the Nuffield Foundation. Acomparison of prednisolone with aspirin and other analgesics in the treatment ofrheumatoid arthritis. Ann Rheum Dis 1960; 19: 331-37.

16. Harris ED, Enikey RD, Nichols JE, Newberg A. Low-dose prednisolone therapy inrheumatoid arthritis a double-blind study. J Rheumatol 1983; 10: 713-21.

17. Co-operating Clinics Committee of the American Rheumatism Association. Acontrolled trial of cyclophosphamide in rheumatoid arthritis. N Engl J Med 1970;283: 883-99.

18. Urowitz MB, Gordon DA, Smythe HA, Pruzanski W, Ogryzlo MA. Azathioprine inrheumatoid arthritis. A double-blind cross-over study. Arthritis Rheum 1973; 16:411-18.

19. Amor B, Mery C. Chlorambucil m rheumatoid arthritis. Clinics Rheum Dis 1980; 6:567-84.

20. Groff DG, Shanberger KN, Wilks WS, Taylor TH. Low-dose oral methotrexate inrheumatoid arthritis an uncontrolled trial and review of the literature. SeminarsArthritis Rheum 1983; 12: 333-47.

21. Kay A. EULAR register of patients on immunosuppressive drugs. Ann Rheum Dis1982; 41 (suppl 1): 30-31.

22. McCarty DJ, Carrera GF. Intractable rheumatoid arthritis. Treatment with combinedcyclophosphamide, azathioprine, and hydroxychloroquine. JAMA 1982; 248:1718-23

Health Watch

MISSING: A NATIONAL HEALTH PROGRAMMEIN THE USA

THE two most frequent questions addressed to Americansin connection with medical care are (a) when will you get anational health service? and (b) why don’t you have a nationalhealth service? Europeans are scandalised by the cost ofmedical care in the USA, the lack ofuniversial coverage, and, ofcourse, the added fear of falling sick while travelling there.They are puzzled as to why such a wealthy country, with suchabundant medical resources, should retain an outmodeduninhibited entrepreneurial system. Almost every otherindustrialised nation, even those with more modest capabilityfor meeting national health needs than the USA, has evolvedsome kind of national health programme. Why not the USA?

It is 75 years since the first rumblings of popular agitationfor a national health programme were heard. At presentpublic interest in the topic seems low. This year’s Democraticpolitical platform has no health plans-so an astute groupingof politicians, who balance off the interests of their