Skip to main content
Annals of the Rheumatic Diseases logoLink to Annals of the Rheumatic Diseases
. 1995 Nov;54(11):881–885. doi: 10.1136/ard.54.11.881

Survival analysis of disease modifying antirheumatic drugs in Spanish rheumatoid arthritis patients.

J De La Mata 1, F J Blanco 1, J J Gómez-Reino 1
PMCID: PMC1010037  PMID: 7492236

Abstract

OBJECTIVES--To evaluate the duration of treatment and the reasons for discontinuing therapy with disease modifying antirheumatic drugs in Spanish rheumatoid arthritis patients. METHODS--An observational study was made of 629 patients with rheumatoid arthritis treated with disease modifying antirheumatic drugs between 1979 and 1991. The outcomes (treatment termination because of toxicity and lack of response) of 991 treatment starts with intramuscular gold salts, D-penicillamine, azathioprine, and methotrexate were subjected to survival analysis. Cumulative probability of continuation of each drug (drug survival) was calculated by the Kaplan-Meier method and comparison between the survival curve of each was made by log rank testing. RESULTS--Median drug survival (95% confidence interval) was 51 (25-76.9) months for methotrexate, 39.9 (19.9-48.2) months for azathioprine, 34.9 (29.4-41.4) months for gold salts, and 16.4 (13.9-21) months for D-penicillamine. The highest cumulative probability of drug survival at five years was for methotrexate (45%); that at 10 years was for gold salts (15%). Up to 60% of the patients discontinued D-penicillamine in the first two years. Lack of response was the major limiting factor for all drugs except D-penicillamine, for which it was toxicity. D-Penicillamine was associated with a greater rate of discontinuations because of toxicity in women and patients older than 65. Previous disease modifying antirheumatic drug administration did not influence current drug survival. CONCLUSION--Overall, gold salts remain useful for the treatment of rheumatoid arthritis over long periods of time in the population studied. Because of the high rate of continuation of treatment (survival) and the optimal efficacy and toxicity profiles observed with methotrexate after five years of treatment, it should be the drug of first choice for second line treatment of these RA patients.

Full text

PDF
881

Selected References

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

  1. Alarcón G. S., Tracy I. C., Blackburn W. D., Jr Methotrexate in rheumatoid arthritis. Toxic effects as the major factor in limiting long-term treatment. Arthritis Rheum. 1989 Jun;32(6):671–676. doi: 10.1002/anr.1780320603. [DOI] [PubMed] [Google Scholar]
  2. Arnold M. H., O'Callaghan J., McCredie M., Beller E. M., Kelly D. E., Brooks P. M. Comparative controlled trial of low-dose weekly methotrexate versus azathioprine in rheumatoid arthritis: 3-year prospective study. Br J Rheumatol. 1990 Apr;29(2):120–125. doi: 10.1093/rheumatology/29.2.120. [DOI] [PubMed] [Google Scholar]
  3. Dixon A. J., Davies J., Dormandy T. L., Hamilton E. B., Holt P. J., Mason R. M., Thompson M., Weber J. C., Zutshi D. W. Synthetic D(-)penicillamine in rheumatoid arthritis. Double-blind controlled study of a high and low dosage regimen. Ann Rheum Dis. 1975 Oct;34(5):416–421. doi: 10.1136/ard.34.5.416. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. 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]
  5. Fries J. F., Williams C. A., Ramey D., Bloch D. A. The relative toxicity of disease-modifying antirheumatic drugs. Arthritis Rheum. 1993 Mar;36(3):297–306. doi: 10.1002/art.1780360303. [DOI] [PubMed] [Google Scholar]
  6. Grindulis K. A., McConkey B. Outcome of attempts to treat rheumatoid arthritis with gold, penicillamine, sulphasalazine, or dapsone. Ann Rheum Dis. 1984 Jun;43(3):398–401. doi: 10.1136/ard.43.3.398. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Hamdy H., McKendry R. J., Mierins E., Liver J. A. Low-dose methotrexate compared with azathioprine in the treatment of rheumatoid arthritis. A twenty-four-week controlled clinical trial. Arthritis Rheum. 1987 Apr;30(4):361–368. doi: 10.1002/art.1780300401. [DOI] [PubMed] [Google Scholar]
  8. Harth M., Davis P., Thompson J. M., Menard H., Beaudet F. Comparison between sodium aurothiomalate and auranofin in rheumatoid arthritis. Results of a two-year open randomized study. Scand J Rheumatol. 1987;16(3):177–184. doi: 10.3109/03009748709165271. [DOI] [PubMed] [Google Scholar]
  9. Husain Z., Runge L. A. Treatment complications of rheumatoid arthritis with gold, hydroxychloroquine, D-penicillamine, and levamisole. J Rheumatol. 1980 Nov-Dec;7(6):825–830. [PubMed] [Google Scholar]
  10. Kremer J. M., Lee J. K. A long-term prospective study of the use of methotrexate in rheumatoid arthritis. Update after a mean of fifty-three months. Arthritis Rheum. 1988 May;31(5):577–584. doi: 10.1002/art.1780310501. [DOI] [PubMed] [Google Scholar]
  11. Kushner I., Dawson N. V. Aggressive therapy does not substantially alter the long-term course of rheumatoid arthritis. So what else is new? Rheum Dis Clin North Am. 1993 Feb;19(1):163–172. [PubMed] [Google Scholar]
  12. Kushner I. Does aggressive therapy of rheumatoid arthritis affect outcome? J Rheumatol. 1989 Jan;16(1):1–4. [PubMed] [Google Scholar]
  13. Paulus H. E., Williams H. J., Ward J. R., Reading J. C., Egger M. J., Coleman M. L., Samuelson C. O., Jr, Willkens R. F., Guttadauria M., Alarcón G. S. Azathioprine versus D-penicillamine in rheumatoid arthritis patients who have been treated unsuccessfully with gold. Arthritis Rheum. 1984 Jul;27(7):721–727. doi: 10.1002/art.1780270701. [DOI] [PubMed] [Google Scholar]
  14. Pincus T., Marcum S. B., Callahan L. F. Longterm drug therapy for rheumatoid arthritis in seven rheumatology private practices: II. Second line drugs and prednisone. J Rheumatol. 1992 Dec;19(12):1885–1894. [PubMed] [Google Scholar]
  15. Pincus T. Rheumatoid arthritis: disappointing long-term outcomes despite successful short-term clinical trials. J Clin Epidemiol. 1988;41(11):1037–1041. doi: 10.1016/0895-4356(88)90072-8. [DOI] [PubMed] [Google Scholar]
  16. Sambrook P. N., Browne C. D., Champion G. D., Day R. O., Vallance J. B., Warwick N. Terminations of treatment with gold sodium thiomalate in rheumatoid arthritis. J Rheumatol. 1982 Nov-Dec;9(6):932–934. [PubMed] [Google Scholar]
  17. Sanchez B., Moreno I., Magariño R., Garzon M., Gonzalez M. F., Garcia A., Nuñez-Roldan A. HLA-DRw10 confers the highest susceptibility to rheumatoid arthritis in a Spanish population. Tissue Antigens. 1990 Oct;36(4):174–176. doi: 10.1111/j.1399-0039.1990.tb01825.x. [DOI] [PubMed] [Google Scholar]
  18. Scott D. L., Symmons D. P., Coulton B. L., Popert A. J. Long-term outcome of treating rheumatoid arthritis: results after 20 years. Lancet. 1987 May 16;1(8542):1108–1111. doi: 10.1016/s0140-6736(87)91672-2. [DOI] [PubMed] [Google Scholar]
  19. Shiokawa Y., Horiuchi Y., Honma M., Kageyama T., Okada T., Azuma T. Clinical evaluation of D-penicillamine by multicentric double-blind comparative study in chronic rheumatoid arthritis. Arthritis Rheum. 1977 Nov-Dec;20(8):1464–1472. doi: 10.1002/art.1780200804. [DOI] [PubMed] [Google Scholar]
  20. Singh G., Fries J. F., Williams C. A., Zatarain E., Spitz P., Bloch D. A. Toxicity profiles of disease modifying antirheumatic drugs in rheumatoid arthritis. J Rheumatol. 1991 Feb;18(2):188–194. [PubMed] [Google Scholar]
  21. Situnayake R. D., Grindulis K. A., McConkey B. Long-term treatment of rheumatoid arthritis with sulphasalazine, gold, or penicillamine: a comparison using life-table methods. Ann Rheum Dis. 1987 Mar;46(3):177–183. doi: 10.1136/ard.46.3.177. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Weinblatt M. E., Coblyn J. S., Fox D. A., Fraser P. A., Holdsworth D. E., Glass D. N., Trentham D. E. Efficacy of low-dose methotrexate in rheumatoid arthritis. N Engl J Med. 1985 Mar 28;312(13):818–822. doi: 10.1056/NEJM198503283121303. [DOI] [PubMed] [Google Scholar]
  23. Weinblatt M. E., Kaplan H., Germain B. F., Block S., Solomon S. D., Merriman R. C., Wolfe F., Wall B., Anderson L., Gall E. Methotrexate in rheumatoid arthritis. A five-year prospective multicenter study. Arthritis Rheum. 1994 Oct;37(10):1492–1498. doi: 10.1002/art.1780371013. [DOI] [PubMed] [Google Scholar]
  24. Wilske K. R., Healey L. A. The need for aggressive therapy of rheumatoid arthritis. Rheum Dis Clin North Am. 1993 Feb;19(1):153–161. [PubMed] [Google Scholar]
  25. 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]
  26. Wooley P. H., Griffin J., Panayi G. S., Batchelor J. R., Welsh K. I., Gibson T. J. HLA-DR antigens and toxic reaction to sodium aurothiomalate and D-penicillamine in patients with rheumatoid arthritis. N Engl J Med. 1980 Aug 7;303(6):300–302. doi: 10.1056/NEJM198008073030602. [DOI] [PubMed] [Google Scholar]
  27. Yelamos J., Garcia-Lozano J. R., Moreno I., Aguilera I., Gonzalez M. F., Garcia A., Nuñez-Roldan A., Sanchez B. Association of HLA-DR4-Dw15 (DRB1*0405) and DR10 with rheumatoid arthritis in a Spanish population. Arthritis Rheum. 1993 Jun;36(6):811–814. doi: 10.1002/art.1780360611. [DOI] [PubMed] [Google Scholar]

Articles from Annals of the Rheumatic Diseases are provided here courtesy of BMJ Publishing Group

RESOURCES