Abstract
OBJECTIVES--To determine the probability of drug continuation in a large cohort of methotrexate treated rheumatoid arthritis (RA) patients, the reasons for discontinuation of methotrexate, the overall survival of the members of this cohort, and the causes of death in these patients. METHODS--Yearly follow up was conducted in methotrexate treated RA patients who formed a cohort between 1981 and 1986 at a tertiary care centre. The probability of drug continuation and the patients' survival were calculated using standard statistical procedures; standardised mortality ratios were calculated using death certificate data and USA general population and mortality tables. RESULTS--The probability of methotrexate continuation at 10 years from the time the first members entered the cohort was 30%. Toxicity (and its severity) was the most frequent cause of discontinuing methotrexate. The cumulative probability of survival was 85% for women and 45% for men. A greater than expected number of deaths from infections was observed, but the number of deaths from cancer and cardiovascular diseases were within the range expected. CONCLUSIONS--Toxicity remains the most common cause for methotrexate discontinuation. Survival was comparable to that of other RA cohorts. Methotrexate may be implicated as an associated factor in the deaths from infections.
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Selected References
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- 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]
- Bridges S. L., Jr, López-Méndez A., Han K. H., Tracy I. C., Alarcón G. S. Should methotrexate be discontinued before elective orthopedic surgery in patients with rheumatoid arthritis? J Rheumatol. 1991 Jul;18(7):984–988. [PubMed] [Google Scholar]
- Gispen J. G., Alarcón G. S., Johnson J. J., Acton R. T., Barger B. O., Koopman W. J. Toxicity of methotrexate in rheumatoid arthritis. J Rheumatol. 1987 Feb;14(1):74–79. [PubMed] [Google Scholar]
- 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]
- Kamel O. W., van de Rijn M., Weiss L. M., Del Zoppo G. J., Hench P. K., Robbins B. A., Montgomery P. G., Warnke R. A., Dorfman R. F. Brief report: reversible lymphomas associated with Epstein-Barr virus occurring during methotrexate therapy for rheumatoid arthritis and dermatomyositis. N Engl J Med. 1993 May 6;328(18):1317–1321. doi: 10.1056/NEJM199305063281806. [DOI] [PubMed] [Google Scholar]
- 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]
- 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]
- MERRELL M., SHULMAN L. E. Determination of prognosis in chronic disease, illustrated by systemic lupus erythematosus. J Chronic Dis. 1955 Jan;1(1):12–32. doi: 10.1016/0021-9681(55)90018-7. [DOI] [PubMed] [Google Scholar]
- Mitchell D. M., Spitz P. W., Young D. Y., Bloch D. A., McShane D. J., Fries J. F. Survival, prognosis, and causes of death in rheumatoid arthritis. Arthritis Rheum. 1986 Jun;29(6):706–714. doi: 10.1002/art.1780290602. [DOI] [PubMed] [Google Scholar]
- Monson R. R., Hall A. P. Mortality among arthritics. J Chronic Dis. 1976 Jul;29(7):459–467. doi: 10.1016/0021-9681(76)90086-2. [DOI] [PubMed] [Google Scholar]
- Morand E. F., McCloud P. I., Littlejohn G. O. Life table analysis of 879 treatment episodes with slow acting antirheumatic drugs in community rheumatology practice. J Rheumatol. 1992 May;19(5):704–708. [PubMed] [Google Scholar]
- Morgan S. L., Baggott J. E., Vaughn W. H., Young P. K., Austin J. V., Krumdieck C. L., Alarcón G. S. The effect of folic acid supplementation on the toxicity of low-dose methotrexate in patients with rheumatoid arthritis. Arthritis Rheum. 1990 Jan;33(1):9–18. doi: 10.1002/art.1780330102. [DOI] [PubMed] [Google Scholar]
- Pincus T., Callahan L. F. Taking mortality in rheumatoid arthritis seriously--predictive markers, socioeconomic status and comorbidity. J Rheumatol. 1986 Oct;13(5):841–845. [PubMed] [Google Scholar]
- Pincus T., Callahan L. F., Vaughn W. K. Questionnaire, walking time and button test measures of functional capacity as predictive markers for mortality in rheumatoid arthritis. J Rheumatol. 1987 Apr;14(2):240–251. [PubMed] [Google Scholar]
- 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]
- 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]
- Seideman P., Müller-Suur R., Ekman E. Renal effects of low dose methotrexate in rheumatoid arthritis. J Rheumatol. 1993 Jul;20(7):1126–1128. [PubMed] [Google Scholar]
- 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]
- Tishler M., Caspi D., Yaron M. Long-term experience with low dose methotrexate in rheumatoid arthritis. Rheumatol Int. 1993;13(3):103–106. doi: 10.1007/BF00290296. [DOI] [PubMed] [Google Scholar]
- Vandenbroucke J. P., Hazevoet H. M., Cats A. Survival and cause of death in rheumatoid arthritis: a 25-year prospective followup. J Rheumatol. 1984 Apr;11(2):158–161. [PubMed] [Google Scholar]
- Walker A. M., Funch D., Dreyer N. A., Tolman K. G., Kremer J. M., Alarcón G. S., Lee R. G., Weinblatt M. E. Determinants of serious liver disease among patients receiving low-dose methotrexate for rheumatoid arthritis. Arthritis Rheum. 1993 Mar;36(3):329–335. doi: 10.1002/art.1780360307. [DOI] [PubMed] [Google Scholar]
- Weinblatt M. E., Trentham D. E., Fraser P. A., Holdsworth D. E., Falchuk K. R., Weissman B. N., Coblyn J. S. Long-term prospective trial of low-dose methotrexate in rheumatoid arthritis. Arthritis Rheum. 1988 Feb;31(2):167–175. doi: 10.1002/art.1780310203. [DOI] [PubMed] [Google Scholar]
- 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]
- 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]
- Wolfe F., Mitchell D. M., Sibley J. T., Fries J. F., Bloch D. A., Williams C. A., Spitz P. W., Haga M., Kleinheksel S. M., Cathey M. A. The mortality of rheumatoid arthritis. Arthritis Rheum. 1994 Apr;37(4):481–494. doi: 10.1002/art.1780370408. [DOI] [PubMed] [Google Scholar]