Summary
From the beginning of 1987 to the end of 1989, 72 rheumatoid arthritis patients (RA) whose disease could not be controlled by a single disease modifying antirheumatic drug (DMARD) were selected for the trial treatment. They continued the DMARD treatment used initially at its regular dose, and then started another DMARD regimen at 1/3 to 1/2 of the regular dose as an additive DMARD treatment, which we have designated as Additive Two DMARD Therapy (ATDT). The patients were followed until the end of 1992. In the 3 months of ATDT, the effectiveness of ATDT was obtained in 42 (58.3%) patients who showed more than a 30% decrease in the initial Lansbury's activity index (AI). The rate of side effects at 3 months were 5.6%. Tiopronin, bucillamine or salazopirine added to gold sodium thiomalate or tiopronin were suggested as the recommended DMARD combinations for ATDT. The suppressive effects on AI, ESR, CRP and rheumatoid factor continued for as long as 18 to 24 months. The mean period of ATDT was 21.7 months and that at which ATDT proved useful was 31.9 months. A discontinuation of the first DMARD treatment without any following disease aggravation was obtained in 10 of 15 patients whose disease activity had been sufficiently suppressed for longer than a year. In conclusion, ATDT was suggested to be a useful way of treating RA patients whose disease activity could not be controlled by a single DMARD treatment, as well as a way of evaluating the next DMARD while the ongoing DMARD was observed to gradually lose its initial drug effect.
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References
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, 33, 1449–1461.
Paulus, H.E. The use of combinations of disease-modifying anti-rheumatic agents in rheumatoid arthritis. Arthritis Rheum 1990, 33, 113–120.
Wilske, K.R., Healey, L.A. Remodeling the pyramid-a concept whose time has come. J Rheumatol 1989, 16, 565–567.
Csuka, M.E., Carrera, G.F., McCarty, D.J. Treatment of intractable rheumatoid arthritis with combined cyclophosphamide, azathioprine and hydroxychloroquine: a follow-up study. JAMA 1986, 255, 2315–2319.
Farr, M., Kitas, G., Bacon, P.A. Sulphasalazine in rheumatoid arthritis: combination therapy with D-penicillamine or sodium aurothiomalate. Clin Rheumatol 1988, 7, 242–248.
Taggart, A.J., Hill, J., Astbury, C., Dixon, J.S., Bird, H.A., Wright, V. Sulphasalazine alone or in combination with D-penicillamine in rheumatoid arthritis. Brit J Rheumatol 1987, 26, 32–36.
Scott, D.L., Dawes, P.T., Tunn, E. et al. Combination therapy with gold and hydroxychloroquine in rheumatoid arthritis: a prospective, randomized, placebo-controlled study. Brit J Rheumatol 1989, 27, 128–133.
Bunch, T.W., O'Duffy, J.D., Tompkins, R.B., O'Fallon, W.M. Controlled trial of hydroxychloroquine and D-penicillamine singly and in combination in the treatment of rheumatoid arthritis. Arthritis Rheum 1984, 28, 267–276.
Dawes, P.T., Sheeran, T.P., Fowler, P.D., Shadforth, M.F. Improving the response to gold or D-penicillamine by addition of sulphasalazine. A pilot study of 25 patients with rheumatoid arthritis. Clin Exp Rheumatol 1987, 5, 151–153.
Gibson, T., Emery, P., Armstrong, R.D., Crisp, A.J., Panayi, G.S. Combined D-penicillamine and chloroquine treatment of rheumatoid arthritis — a comparative study. Brit J Rheumatol 1987, 26, 279–284.
Yasuda, M., Nobunaga, M. Treatment of the patients with rheumatoid arthritis using two disease modifying antirheumatic drugs (Two DMARD Therapy). Magyar Rheumatologia 1991, suppl 32, 46.
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, 9, 175–176.
Lansbury, J. Methods for evaluating rheumatoid arthritis. In: Arthritis & Allied Conditions, 7th ed., Ed.: Hollander, J.L. Philadelphia, Lea & Febiger, 1966, 269–291.
Ishikawa, K., Sakaguchi, M. SA96 (N-(2-mercapto-2-methylpropanoyl)-1-cysteine) in rheumatoid arthritis. Scan J Rheumatol 1986, 15, 85–90.
Amor, B., Mery, C., de Gery, A. Tiopronin(n-[2-mercaptopropionyl] glycin) in rheumatoid arthritis. Arthritis Rheum 1982, 25, 698–703.
Shiokawa, Y., Horiuchi, Y., Mizushima, Y., Kageyama, Y., Shichikawa, K., Ofuji, T., et al. A multicenter double-blind controlled study of lobenzarit, a novel immunomodulator, in rheumatoid arthritis. J Rheumatol 1984, 11, 615–623.
Anderson, J.J., Felson, D.T., Meenan, R.F., Williams, H.J. Which traditional measures should be used in rheumatoid clinical trials? Arthritis Rheum 1989, 32, 1093–1099.
Yasuda, M., Nobunaga, M. Treatment of patients with rheumatoid arthritis (RA) by a new disease modifying anti-rheumatic drug (DMARD), bucillamine(Buc), alone and in combination with another DMARD. Scand J Rheumatol 1990, suppl 85, 47.
Furst, D.E., Levine, S., Srinivasan, R., Metzger, A.L., Bangert, R., Paulus, H.E. A double-blind trial of high versus conventional dosages of gold salts for rheumatoid arthritis. Arthritis Rheum 1977, 20, 1473–1480.
Tournade, H., Guery, J-C., Pasquier, R., et al. Effect of the thiol group on experimental gold-induced autoimmunity. Arthritis Rheum 1991, 34, 1594–1599.
Lazarevic, M.B., Yan, K., Swedler, W.I., Rasenick, M.M., Skosey, J.L. Effect of gold compounds on the activity of adenylyl cyclase in human lymphocyte membranes. Arthritis Rheum 1992, 35, 857–864.
Williams, H.J., Ward, J.R., Reading, J.C., Brooks, R.H., Clegg, D.O., Skosey, J.L., et al. Comparison of auranofin, methotrexate, and the combination of both in the treatment of rheumatoid arthritis. A controlled clinical trial. Arthritis Rheum 1992, 35, 259–269.
Kantor, S.M., Wallin, B.A., Grier, C.E., McCafferty, J.P., Wetherington, J.D., Fox, M.J., et al. Combination of auranofin and methotrexate as initial DMARD therapy in RA. Magyar Rheumatol 1991, suppl 32, 138.
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, 17, 994–1002.
Pincus, T., Marcum, S.B., Callahan, L.F. Long-term drug therapy for rheumatoid arthritis in seven rheumatology private practices: II. Second line drugs and prednisone. J Rheumatol 1992, 19, 1885–1894.
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, 19, 704–708.
Murayama, T., Ubukata, A., Nakazaki, S. Comparative study on immunomodulating drugs for rheumatoid arthritis. — A long term study by the method of life-table analysis. Jpn J Clin Immunol 1989, 12, 386–393.
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Yasuda, M., Nonaka, S., Wada, T. et al. Additive two DMARD therapy of the patients with rheumatoid arthritis. Clin Rheumatol 13, 446–454 (1994). https://doi.org/10.1007/BF02242941
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DOI: https://doi.org/10.1007/BF02242941