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. 1999 May;58(5):281–287. doi: 10.1136/ard.58.5.281

Prospective six year follow up of patients withdrawn from a randomised study comparing parenteral gold salt and methotrexate

O Sander 1, G Herborn 1, E Bock 1, R Rau 1
PMCID: PMC1752873  PMID: 10225812

Abstract

OBJECTIVE—To confirm the impression of a better outcome of patients withdrawn from parenteral gold salt therapy compared with those withdrawn from methotrexate.
METHODS—Patients with early, active, and erosive RA were randomised for a double blind trial to receive either weekly 15 mg intramuscular methotrexate or 50 mg goldsodiumthiomalate. If the drug had to be withdrawn because of side effects treatment was continued with the other drug in still active disease. Patients with insufficient response were treated with a combination of both drugs. All patients were followed up by an extended clinical and radiographic evaluation.
RESULTS—64 patients each were allocated to methotrexate and gold treatment. After 72 months a complete record was available for 88% of patients. Within the first 36 months 38 patients withdrew from gold treatment (95% because of side effects) and 23 patients withdrew from methotrexate (57% because of side effects). A significant 40% to 70% improvement of all parameters (erythrocyte sedimentation rate, C reactive protein, swollen and tender joints, radiological progression) compared with baseline was observed in patients completing their randomised treatment with gold or methotrexate. The same improvement over three years was seen in patients who withdrew from gold treatment, while patients withdrawing from methotrexate experienced a deterioration of their disease.
CONCLUSION—Withdrawals represent the majority of patients in long term drug trials. Patients with early RA stopping gold because of side effects show almost the same sustained improvement as patients continuing gold or methotrexate. Patients withdrawn from methotrexate experience a reactivation of their disease.



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Figure 1  .

Figure 1  

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(A) Proportion of patients with good response according to the EULAR criteria in completers and withdrawals (GSTM and MTX). (B) Proportion of patients with moderate response according to the EULAR criteria in completers and withdrawals (GSTM and MTX).

Figure 2  .

Figure 2  

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Swollen joint count in completers and withdrawals (GSTM and MTX). Response to treatment shown as percentage of baseline.

Figure 3  .

Figure 3  

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C reactive protein in completers and withdrawals (GSTM and MTX). Response to treatment shown as percentage of baseline.

Figure 4  .

Figure 4  

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Slope of radiological deterioration in completers and withdrawals (GSTM and MTX). Average increase in Ratingen score per month.

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. ADAMS C. H., CECIL R. L. Gold therapy in early rheumatoid arthritis. Ann Intern Med. 1950 Jul;33(1):163–173. doi: 10.7326/0003-4819-33-1-163. [DOI] [PubMed] [Google Scholar]
  2. Buckland-Wright J. C., Clarke G. S., Chikanza I. C., Grahame R. Quantitative microfocal radiography detects changes in erosion area in patients with early rheumatoid arthritis treated with myocrisine. J Rheumatol. 1993 Feb;20(2):243–247. [PubMed] [Google Scholar]
  3. Buckland-Wright J. C., Clarke G. S., Walker S. R. Erosion number and area progression in the wrists and hands of rheumatoid patients: a quantitative microfocal radiographic study. Ann Rheum Dis. 1989 Jan;48(1):25–29. doi: 10.1136/ard.48.1.25. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Caspi D., Tishler M., Yaron M. Association between gold induced skin rash and remission in patients with rheumatoid arthritis. Ann Rheum Dis. 1989 Sep;48(9):730–732. doi: 10.1136/ard.48.9.730. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Cats A. A multicentre controlled trial of the effects of different dosage of gold therapy, followed by a maintenance dosage. Agents Actions. 1976 Feb;6(1-3):355–363. doi: 10.1007/BF01972255. [DOI] [PubMed] [Google Scholar]
  6. De La Mata J., Blanco F. J., Gómez-Reino J. J. Survival analysis of disease modifying antirheumatic drugs in Spanish rheumatoid arthritis patients. Ann Rheum Dis. 1995 Nov;54(11):881–885. doi: 10.1136/ard.54.11.881. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Del Papa N., Guidali L., Sala A., Buccellati C., Khamashta M. A., Ichikawa K., Koike T., Balestrieri G., Tincani A., Hughes G. R. Endothelial cells as target for antiphospholipid antibodies. Human polyclonal and monoclonal anti-beta 2-glycoprotein I antibodies react in vitro with endothelial cells through adherent beta 2-glycoprotein I and induce endothelial activation. Arthritis Rheum. 1997 Mar;40(3):551–561. doi: 10.1002/art.1780400322. [DOI] [PubMed] [Google Scholar]
  8. Del Papa N., Guidali L., Sala A., Buccellati C., Khamashta M. A., Ichikawa K., Koike T., Balestrieri G., Tincani A., Hughes G. R. Endothelial cells as target for antiphospholipid antibodies. Human polyclonal and monoclonal anti-beta 2-glycoprotein I antibodies react in vitro with endothelial cells through adherent beta 2-glycoprotein I and induce endothelial activation. Arthritis Rheum. 1997 Mar;40(3):551–561. doi: 10.1002/art.1780400322. [DOI] [PubMed] [Google Scholar]
  9. Drosos A. A., Karantanas A. H., Psychos D., Tsampoulas C., Moutsopoulos H. M. Can treatment with methotrexate influence the radiological progression of rheumatoid arthritis? Clin Rheumatol. 1990 Sep;9(3):342–345. doi: 10.1007/BF02114394. [DOI] [PubMed] [Google Scholar]
  10. Felson D. T., Anderson J. J., Meenan R. F. The comparative efficacy and toxicity of second-line drugs in rheumatoid arthritis. Results of two metaanalyses. Arthritis Rheum. 1990 Oct;33(10):1449–1461. doi: 10.1002/art.1780331001. [DOI] [PubMed] [Google Scholar]
  11. Hanrahan P. S., Scrivens G. A., Russell A. S. Prospective long term follow-up of methotrexate therapy in rheumatoid arthritis: toxicity, efficacy and radiological progression. Br J Rheumatol. 1989 Apr;28(2):147–153. doi: 10.1093/rheumatology/28.2.147. [DOI] [PubMed] [Google Scholar]
  12. Hoffmeister R. T. Methotrexate therapy in rheumatoid arthritis: 15 years experience. Am J Med. 1983 Dec 30;75(6A):69–73. doi: 10.1016/0002-9343(83)90477-1. [DOI] [PubMed] [Google Scholar]
  13. Klinkhoff A. V., Teufel A. How low can you go? Use of very low dosage of gold in patients with mucocutaneous reactions. J Rheumatol. 1995 Sep;22(9):1657–1659. [PubMed] [Google Scholar]
  14. Klinkhoff A. V., Teufel A. The second course of gold. J Rheumatol. 1995 Sep;22(9):1655–1656. [PubMed] [Google Scholar]
  15. Kremer J. M., Phelps C. T. Long-term prospective study of the use of methotrexate in the treatment of rheumatoid arthritis. Update after a mean of 90 months. Arthritis Rheum. 1992 Feb;35(2):138–145. doi: 10.1002/art.1780350203. [DOI] [PubMed] [Google Scholar]
  16. Larsen A., Dale K., Eek M. Radiographic evaluation of rheumatoid arthritis and related conditions by standard reference films. Acta Radiol Diagn (Stockh) 1977 Jul;18(4):481–491. doi: 10.1177/028418517701800415. [DOI] [PubMed] [Google Scholar]
  17. Larsen A., Horton J., Howland C. The effects of auranofin and parenteral gold in the treatment of rheumatoid arthritis: an X-ray analysis. Clin Rheumatol. 1984 Mar;3 (Suppl 1):97–104. doi: 10.1007/BF03342627. [DOI] [PubMed] [Google Scholar]
  18. Lockie L. M., Smith D. M. Forty-seven years experience with gold therapy in 1,019 rheumatoid arthritis patients. Semin Arthritis Rheum. 1985 May;14(4):238–246. doi: 10.1016/0049-0172(85)90043-5. [DOI] [PubMed] [Google Scholar]
  19. Luukkainen R., Kajander A., Isomäki H. Effect of gold on progression of erosions in rheumatoid arthritis. Better results with early treatment. Scand J Rheumatol. 1977;6(3):189–192. doi: 10.3109/03009747709095448. [DOI] [PubMed] [Google Scholar]
  20. Menninger H., Herborn G., Sander O., Blechschmidt J., Rau R. A 36 month comparative trial of methotrexate and gold sodium thiomalate in the treatment of early active and erosive rheumatoid arthritis. Br J Rheumatol. 1998 Oct;37(10):1060–1068. doi: 10.1093/rheumatology/37.10.1060. [DOI] [PubMed] [Google Scholar]
  21. Morassut P., Goldstein R., Cyr M., Karsh J., McKendry R. J. Gold sodium thiomalate compared to low dose methotrexate in the treatment of rheumatoid arthritis--a randomized, double blind 26-week trial. J Rheumatol. 1989 Mar;16(3):302–306. [PubMed] [Google Scholar]
  22. ROPES M. W., BENNETT G. A., COBB S., JACOX R., JESSAR R. A. 1958 Revision of diagnostic criteria for rheumatoid arthritis. Bull Rheum Dis. 1958 Dec;9(4):175–176. [PubMed] [Google Scholar]
  23. Rau R., Herborn G., Menninger H., Blechschmidt J. Comparison of intramuscular methotrexate and gold sodium thiomalate in the treatment of early erosive rheumatoid arthritis: 12 month data of a double-blind parallel study of 174 patients. Br J Rheumatol. 1997 Mar;36(3):345–352. doi: 10.1093/rheumatology/36.3.345. [DOI] [PubMed] [Google Scholar]
  24. Rau R., Herborn G., Menninger H., Sangha O. Progression in early erosive rheumatoid arthritis: 12 month results from a randomized controlled trial comparing methotrexate and gold sodium thiomalate. Br J Rheumatol. 1998 Nov;37(11):1220–1226. doi: 10.1093/rheumatology/37.11.1220. [DOI] [PubMed] [Google Scholar]
  25. Rau R., Schleusser B., Herborn G., Karger T. Long-term treatment of destructive rheumatoid arthritis with methotrexate. J Rheumatol. 1997 Oct;24(10):1881–1889. [PubMed] [Google Scholar]
  26. Rau R., Wassenberg S., Herborn G., Stucki G., Gebler A. A new method of scoring radiographic change in rheumatoid arthritis. J Rheumatol. 1998 Nov;25(11):2094–2107. [PubMed] [Google Scholar]
  27. Reykdal S., Steinsson K., Sigurjónsson K., Brekkan A. Methotrexate treatment of rheumatoid arthritis: effects on radiological progression. Scand J Rheumatol. 1989;18(4):221–226. doi: 10.3109/03009748909099932. [DOI] [PubMed] [Google Scholar]
  28. Sany J., Anaya J. M., Lussiez V., Couret M., Combe B., Daures J. P. Treatment of rheumatoid arthritis with methotrexate: a prospective open longterm study of 191 cases. J Rheumatol. 1991 Sep;18(9):1323–1327. [PubMed] [Google Scholar]
  29. Sharp J. T., Lidsky M. D., Duffy J. Clinical responses during gold therapy for rheumatoid arthritis. Changes in synovitis, radiologically detectable erosive lesions, serum proteins, and serologic abnormalities. Arthritis Rheum. 1982 May;25(5):540–549. doi: 10.1002/art.1780250508. [DOI] [PubMed] [Google Scholar]
  30. Sigler J. W., Bluhm G. B., Duncan H., Sharp J. T., Ensign D. C., McCrum W. R. Gold salts in the treatment of rheumatoid arthritis. A double-blind study. Ann Intern Med. 1974 Jan;80(1):21–26. doi: 10.7326/0003-4819-80-1-21. [DOI] [PubMed] [Google Scholar]
  31. Srinivasan R., Miller B. L., Paulus H. E. Long-term chrysotherapy in rheumatoid arthritis. Arthritis Rheum. 1979 Feb;22(2):105–110. doi: 10.1002/art.1780220201. [DOI] [PubMed] [Google Scholar]
  32. Suarez-Almazor M. E., Fitzgerald A., Grace M., Russell A. S. A randomized controlled trial of parenteral methotrexate compared with sodium aurothiomalate (Myochrysine) in the treatment of rheumatoid arthritis. J Rheumatol. 1988;15(5):753–756. [PubMed] [Google Scholar]
  33. Suarez-Almazor M. E., Soskolne C. L., Saunders L. D., Russell A. S. Use of second line drugs for the treatment of rheumatoid arthritis in Edmonton, Alberta. Patterns of prescription and longterm effectiveness. J Rheumatol. 1995 May;22(5):836–843. [PubMed] [Google Scholar]
  34. Svensson A., Theander J. Skin rashes and stomatitis due to parenteral treatment of rheumatoid arthritis with sodium aurothiomalate. Ann Rheum Dis. 1992 Mar;51(3):326–329. doi: 10.1136/ard.51.3.326. [DOI] [PMC free article] [PubMed] [Google Scholar]
  35. Weinblatt M. E., Weissman B. N., Holdsworth D. E., Fraser P. A., Maier A. L., Falchuk K. R., Coblyn J. S. Long-term prospective study of methotrexate in the treatment of rheumatoid arthritis. 84-month update. Arthritis Rheum. 1992 Feb;35(2):129–137. doi: 10.1002/art.1780350202. [DOI] [PubMed] [Google Scholar]
  36. Wolfe F., Hawley D. J., Cathey M. A. Termination of slow acting antirheumatic therapy in rheumatoid arthritis: a 14-year prospective evaluation of 1017 consecutive starts. J Rheumatol. 1990 Aug;17(8):994–1002. [PubMed] [Google Scholar]
  37. ten Wolde S., Breedveld F. C., Hermans J., Vandenbroucke J. P., van de Laar M. A., Markusse H. M., Janssen M., van den Brink H. R., Dijkmans B. A. Randomised placebo-controlled study of stopping second-line drugs in rheumatoid arthritis. Lancet. 1996 Feb 10;347(8998):347–352. doi: 10.1016/s0140-6736(96)90535-8. [DOI] [PubMed] [Google Scholar]
  38. ten Wolde S., Hermans J., Breedveld F. C., Dijkmans B. A. Effect of resumption of second line drugs in patients with rheumatoid arthritis that flared up after treatment discontinuation. Ann Rheum Dis. 1997 Apr;56(4):235–239. doi: 10.1136/ard.56.4.235. [DOI] [PMC free article] [PubMed] [Google Scholar]
  39. van Gestel A. M., Prevoo M. L., van 't Hof M. A., van Rijswijk M. H., van de Putte L. B., van Riel P. L. Development and validation of the European League Against Rheumatism response criteria for rheumatoid arthritis. Comparison with the preliminary American College of Rheumatology and the World Health Organization/International League Against Rheumatism Criteria. Arthritis Rheum. 1996 Jan;39(1):34–40. doi: 10.1002/art.1780390105. [DOI] [PubMed] [Google Scholar]
  40. van Gestel A., Koopman R., Wijnands M., van de Putte L., van Riel P. Mucocutaneous reactions to gold: a prospective study of 74 patients with rheumatoid arthritis. J Rheumatol. 1994 Oct;21(10):1814–1819. [PubMed] [Google Scholar]

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