Skip to main content
Log in

Experience with low-dose methotrexate: Toxicity, tolerability and effect on conventional patterns of drug therapy for inflammatory arthritis

  • Published:
Clinical Rheumatology Aims and scope Submit manuscript

Summary

This study examines the 10-year experience of a single rheumatologist in the treatment of inflammatory arthritis with low dose methotrexate (MTX). The toxicity and tolerability of MTX has been assessed and the effect of this drug on the conventional pattern of pharmacotherapy for inflammatory arthritis has been examined. The case records of all 99 patients with inflammatory arthritis prescribed MTX in the ten-year period up to the end of 1991 were reviewed. Adverse reactions, duration of therapy, overall efficacy, as well as details of previous and concurrent drug therapy were noted.

MTX was clinically beneficial in 85 patients. Of these, on a four point scale, 68 patients claimed moderate or marked benefit. MTX was discontinued in 20 patients; in 12 the cause was an adverse reaction. Many more (47) patients suggered mild reactions not resulting in drug withdrawal. In our patients MTX has a favourable tolerability record and has been continued in 83%, 69% and 50% after 1, 2, and 5 years of treatment respectively. The use of MTX increased markedly towards the end of the 10-year study period. Sixty-two patients were started on MTX either in 1990 or 1991. The mean number of other disease modifying drugs used before MTX has declined from a peak of 2.40 in 1987 in 1987 to 1.52 in 1991. Similarly, the percentage of patients prescribed concurrent oral corticosteroids has declined from 88% to 52% from 1987 to 1991.

In our experience MTX is effective, has a favourable toxicity and tolerability record. In this practice we have identified a trend to increased use of MTX earlier in the course of drug treatment of inflammatory arthritis. The concurrent use of oral corticosteroids appears to be declining.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Similar content being viewed by others

References

  1. 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, 312, 818–822.

    Google Scholar 

  2. Thompson, R.M., Watts, C., Edelman, J., Esdaile, J., Russell, A.S. A controlled two centre trial of parenteral methotrexate therapy for refractory rheumatoid arthritis. J Rheumatol 1984 11, 760–763.

    Google Scholar 

  3. Williams, H.J., Willkens, R.E., Samuelson, C.O. Jr., Alarcon, G.S., Guttadauria, M., Yarboro, C. et al. Comparison of low-dose oral pulse methotrexate and placebo in the treatment of rheumatoid arthritis: a controlled clinical trial. Arthritis Rheum 1985, 28, 721–730.

    Google Scholar 

  4. Anderson, P.A., West, S.G., O'Dell, J.R., Via, C.S., Claypool, R.G., Kotzin, B.L., Weekly pulse methotrexate in rheumatoid arthritis: clinical and immunologic effects in a randomised double study. Ann Intern Med 1985, 103, 489–496.

    Google Scholar 

  5. Hoffmeister, R.T. Methotrexate therapy in rheumatoid arthritis: 15 years experience. Am J Med (suppl 6A) 1983, 75, 6973.

    Google Scholar 

  6. Weinstein, A., Marlowe, S., Korn, J., Faronhar, F. Low dose methotrexate treatment of rheumatoid arthritis: long-term observations. Am J Med 1985, 79, 331–337.

    Google Scholar 

  7. Fehlauer, C.S., Carson, C.W., Cannon, G.W., Ward, J.R., Samuelson, C.O., Williams, H.J., Clegg, D.O. Methotrexate therapy in rheumatoid arthritis: 2-year retrospective follow-up study. J Rheumatol 1989, 16, 307–312.

    Google Scholar 

  8. Kremer, J.M., Lee, J.K. The safety and efficacy of the use of methotrexate in the long-term therapy for rheumatoid arthritis. Arthritis Rheum 1986, 29, 822–831.

    Google Scholar 

  9. Weinblatt, M.E., Weissman, B.N., Holdsworth, D.E., Long term prospective study of methotrexate in the treatment of rheumatoid arthritis. 84-month update. Arthritis Rheum 1992, 35, 129–137.

    Google Scholar 

  10. Kremer, J., 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, 35, 138145.

    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, 28, 147–153.

    Google Scholar 

  12. Weinblatt, M.E., Kaplan, H., Germain, B.F., Merriman, R.C., Soloman, S.D., Wall, B. et al. Methotrexate in rheumatoid arthritis: effects on disease activity in a multicenter prospective study. J Rheumatol 1991, 18, 334–338.

    Google Scholar 

  13. Hamdy, H., McKendry, R.J.R., 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, 30, 361–368.

    Google Scholar 

  14. Morrasut, 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 randomised, double blind 26-week trial. J Rheumatol 1989, 16, 302–306.

    Google Scholar 

  15. Weinblatt, M.E., Kaplan, H., Germain, B.F., Merriman, R.C., Soloman, S.D., Wall, B. et al. Low-dose methotrexate compared with auranofin in adult rheumatoid arthritis: a thirty-six week double blind trial. Arthritis Rheum 1990, 33, 330–338.

    Google Scholar 

  16. Kremer, J.M., Rynes, R.I., Bartholomew, L.E. Severe flare of rheumatoid arthritis after discontinuation of long-term methotrexate therapy: double blind study. Am J Med 1987, 82, 781786.

    Google Scholar 

  17. 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, 18, 188–194.

    Google Scholar 

  18. Wolf, F., Hawley, D.J., Cathey, M.E. Termination of slow acting antirheumatic therapy in rheumatoid arthritis: a 14-year prospective evaluation of 1017 consecutive starts. J Rheumatol 1990, 17, 994–1002.

    Google Scholar 

  19. Wilkske, K., Healey, L. Remodeling the pyramid: a concept whose time has come. J Rheumatol 1989, 16, 565–567.

    Google Scholar 

  20. Furst, D.E., Koehnke, R., Burmeister, L.F., Kohler, J., Cargill, I. Increasing methotrexate effect with increasing dose in the treatment of resistant rheumatoid arthritis. J Rheumatol 1989, 16, 313–320.

    Google Scholar 

  21. Alarcon, 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, 32, 671–676.

    Google Scholar 

  22. Sany, J., Anaya, J.M., Lussiez, V., Couret, M., Combe, B., Daures, J.P. Treatment of rheumatoid arthritis with methotrexate: a prospective open long-term study of 191 cases. J Rheumatol 1991, 18, 1323–1327.

    Google Scholar 

  23. Kremer, J.M., Lee, R.G., Tolman, K.G. Liver histology in rheumatoid arthritis patients receiving long-term methotrexate therapy. A prospective study with baseline and sequential biopsy samples. Arthritis Rheum 1989, 32, 121–127.

    Google Scholar 

  24. Bridges, S.L., Alarcon, G.S., Koopman, W.J. Methotrexate-induced liver abnormalities in rheumatoid arthritis. J Rheumatol 1989, 16, 1180–1183.

    Google Scholar 

  25. Aponte, J., Petrelli, M. Histopathologic findings in the liver of rheumatoid arthritis patients treated with long-term bolus methotrexate. Arthritis Rheum 1988, 31, 1457–1464.

    Google Scholar 

  26. Kremer, J.M., Alarcon, G.S., Lightfoot, R.W. et al. Methotrexate for rheumatoid arthritis. Suggested guidelines for monitoring liver toxicity. Arthritis Rheum 1994, 37, 316–328.

    Google Scholar 

  27. MacKinnon, S.A., Starkebaum, G., Willkens, R.F. Pancytopenia associated with low dose pulse methotrexate in the treatment of rheumatoid arthritis. Semin Arthritis Rheum 1985, 15, 119–126.

    Google Scholar 

  28. Carson, C.W., Cannon, G.W., Egger, M.J., Ward, J.R., Clegg, D.O. Pulmonary disease during the treatment of rheumatoid arthritis with low dose pulse methotrexate. Semin Arthritis Rheum 1987, 16, 186–195.

    Google Scholar 

  29. Cannon, G.W., Ward, J.R., Clegg, D.O., Samuelson, C.O. Jr., Abbot, T.M. Acute lung disease associated with low-dose pulse methotrexate therapy in patients with rheumatoid arthritis. Arthritis Rheum 1983, 26, 1269–1274.

    Google Scholar 

  30. Golden, M.R., Katz, R.S., Balk, R.A., Neu, J., Golden, H. The relationship of pre-existing lung disease to the occurrence of methotrexate pneumonitis in rheumatoid arthritis patients. Arthritis Rheum 1990, 33 (suppl 9), S40.

    Google Scholar 

  31. Symmons, D.P.M. Neoplasia in rheumatoid arthritis. J Rheumatol 1988, 15, 1319–1322.

    Google Scholar 

  32. Kamel, O.W., Van De Rijn, M., Weiss, L.M. et al. Reversible lymphomas associated with Epstein-Barr virus occurring during methotrexate therapy for rheumatoid arthritis and dermatomyositis. New Eng J Med 1993, 328, 1317–1321.

    Google Scholar 

  33. Duncan, I.J.S., Hurst, N.P. A multiple life table analysis comparing anti-rheumatic drugs: is methotrexate the antirheumatic drug (ARD) of first choice? Br J Rheumatol 1989, (suppl 2), 28, 118–119.

    Google Scholar 

  34. 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, 46, 117–183.

    Google Scholar 

  35. Kushner, I., Dawson, N.V. Changing perspectives in the treatment of rheumatoid arthritis. J Rheumatol 1992, 19, 18311833.

    Google Scholar 

  36. Wilske, K.R., Healey, L.A. Challenging the therapeutic pyramid: a new look at treatment strategies for rheumatoid arthritis. J Rheumatol 1990, 17, 4–7.

    Google Scholar 

  37. Spector, T.D., Thompson, P.W., Evans, S.J.W., Scott, D.L. Are slow-acting antirheumatic drugs being given earlier in rheumatoid arthritis? Br J Rheumatol 1988, 27, 498499.

    Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Rights and permissions

Reprints and permissions

About this article

Cite this article

Nisar, M., Carlisle, L. & Amos, R. Experience with low-dose methotrexate: Toxicity, tolerability and effect on conventional patterns of drug therapy for inflammatory arthritis. Clin Rheumatol 14, 544–550 (1995). https://doi.org/10.1007/BF02208152

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF02208152

Key words

Navigation