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Disparity between clinical and immune responses in a controlled trial of azathioprine in rheumatoid arthritis

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Summary

Drugs that interfere with the immune responsein vitro, such as azathioprine (AZ), have been used extensively since 1964 in clinical therapeutic trials of autoimmune diseases. However, few adequately controlled studies are available concerning the concurrent effect of AZ on the immune and clinical responses to treatment of rheumatoid arthritis (RA). Thirty patients suffering from classical seropositive RA received AZ (1.5 – 2.0 mg/kg/day) and placebo in a controlled clinical cross-over study for two 12-week periods. Other treatments were kept constant throughout the entire 6 months. In terms of the clinical responses of joint count and grip strength patients receiving AZ improved markedly, in contrast to the placebo group. After 2 months, joint scanning revealed no progress of the disease in patients undergoing AZ treatment. Corresponding with the remarkably beneficial clinical effect of AZ, a significant drop in immunoglobulins was observed. However, since AZ failed to suppressin vivo specific antibody synthesis in RA, the question remains as to whether this drug actually does interfere with the autoimmunogenesis of the disease.

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References

  1. Butler, W.T., Rossen, R.D.: Effects of corticosteroids on immunity in man. J. clin. Invest.52 2629–2640 (1973)

    Google Scholar 

  2. Cridland, M.D.: Antineoplastic and immunosuppressive drugs. III. Adverse effects and therapeutic problems. Drugs3 352–365 (1972)

    Google Scholar 

  3. Currey, H.L.F., Harris, J., Mason, R.M., Woodland, J.M., Beveridge, T., Roberts, C.J., Vere, D.W., Dixon, A.St.J., Davies, J., Owen-Smith, B.: Comparison of azathioprine, cyclophosphamide, and gold in treatment of rheumatoid arthritis. Brit. med. J.1974 III 763–766

    Google Scholar 

  4. Ganner, E., Osment, J., Dittrich, P., Huber, H.: Chromosomes in patients treated with azathioprine. Hum. Genet.18 231–236 (1973)

    Google Scholar 

  5. Goebel, K.M., Gassel, W.D., Goebel, F.D.: Evaluation of azathioprine in autoimmune thrombocytopenia and lupus erythematodes. Scand. J. Haemat.10 28–34 (1973)

    Google Scholar 

  6. Goebel, K.M., Goebel, F.D., Gassel, W.D., Neitzert, A., Mueller, K.: Immune response in patients with autoimmune thrombocytopenia and autoimmune haemolytic anaemia receiving azathioprine. Klin. Wschr.52 916–920 (1974)

    Google Scholar 

  7. Harris, J., Jessop, J.D., Saintonge, D.M.: Further experience with azathioprine in rheumatoid arthritis. Brit. med. J.1971 IV 463–464

    Google Scholar 

  8. Hitchings, G.H., Elion, G.B.: Some aspects of immunosuppression. Ann. N. Y. Acad. Sci.129 799–803 (1966)

    Google Scholar 

  9. Jones, J.M., Martinez, A.J., Joshi, V.V., McWilliams, N.: Systemic lupus erythematosus. Clinical neuropathologic correlation. Arch. Path.99 152–157 (1975)

    Google Scholar 

  10. Kripke, M.L., Borsos, T.: Immunsuppression and carcinogenesis. Israel J. med. Sci.10 888–903 (1974)

    Google Scholar 

  11. Lansbury, J.: Methods for evaluating rheumatoid arthritis. In: Arthritis & allied conditions (ed. J.L. Hollander), pp. 781–845. Philadelphia: Lea & Febinger 1966

    Google Scholar 

  12. Levy, J., Barnett, E.V., Mac Donals, N.S., Klinenberg, J.R., Pearson, C.M.: The effects of azathioprine on gammaglobulin synthesis in man. J. clin. Invest.51 2233–2238 (1972)

    Google Scholar 

  13. Mason, M., Currey, H.L.F., Barnes, C.G., Dunne, J.F., Zazleman, B.L., Strickland, I.D.: Azathioprine in rheumatoid arthritis. Brit. med. J.1969 I 420–422

    Google Scholar 

  14. Moore, G., Harley, J.P., Otero, R.: Immunosuppressive activity of azathioprine in experimental infection of the mouse with trichinella spiralis. Experientia (Basel)30 952–953 (1974)

    Google Scholar 

  15. Rampon, S., Bussiere, J.L., Prin, Ph., Sauvezie, P., Leroy, V., Missioux, D., Doly, J., Suss, P., Jourde, H., Lapalus, F.: A propos de 250 observations de scintigraphie osseuse par le pyrophsphate d'etain marque au technetium 99 m. Rev. Rhum.41 745–751 (1974)

    Google Scholar 

  16. Ricken, D., Marsteller, H.J., Baack, G.: Immunsuppressive Behandlung der primär chronischen Polyarthritis und des Lupus erythematodes disseminatus. Med. Welt22 1501–1506 (1971)

    Google Scholar 

  17. Ropes, M.W., Benett, G.A., Cobb, S.: Revision of diagnostic criteria for rheumatoid arthritis. Bull. rheum. Dis.9 175–176 (1958)

    Google Scholar 

  18. Savage, O.: Measurements in rheumatoid arthritis. Proc. roy. Soc. Med.59 (Suppl. 85), (1966)

  19. Scheiffarth, F., Warnatz, H.: Medikamentöse Immunsuppression der primär-chronischen Polyarthritis. In: Medikamentöse Immunsuppression (eds. D. Ricken, K. Schumacher), pp. 93–104. Stuttgart: Thieme 1971

    Google Scholar 

  20. Schumacher, H.R.: Synovial membrane and fluid morphologic alterations in early rheumatoid arthritis: Microvascular injury and virus-like particles. Ann. N. Y. Acad. Sci.256 39–65 (1975)

    Google Scholar 

  21. Stiller, C.R., Russel, A.S., Dossetor, J.B.: Autoimmunity: Present concepts. Ann. intern. Med.82 405–410 (1975)

    Google Scholar 

  22. Swanson, M.A., Schwartz, R.S.: Immunosuppressive therapy. The relation between clinical response and immunologic competence. New Engl. J. Med.277 163–170 (1967)

    Google Scholar 

  23. Tausch, G., Siegmeth, W.: Weitere Ergebnisse der Langzeittherapie mit Azathioprine bei erosiven Fällen von chronischer Polyarthritis. Z. Rheumaforsch.32 344–354 (1973)

    Google Scholar 

  24. Urowitz, M.B., Gordon, D.A., Smythe, H.A., Pruzanski, W., Ogryzlo, M.A.: Azathioprine in rheumatoid arthritis. Arthr. and Rheum.16 411–418 (1973)

    Google Scholar 

  25. Urowitz, M.B., Hunter, T., Bookman, A.A.M., Gordon, D.A., Smythe, H.A., Ogryzlo, M.A.: Azathioprine in rheumatoid arthritis. A double blind study comparing full dose to half dose. J. Rheum.1 274–281 (1974)

    Google Scholar 

  26. Wirth, W., Müller, U.St., Thöne, F.: Untersuchungen zum Wirkungsmechanismus sogenannter Immunsuppressiva. Arzneimittelallergie (Suppl.)1 282–287 (1974)

    Google Scholar 

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Goebel, K.M., Janzen, R., Joseph, K. et al. Disparity between clinical and immune responses in a controlled trial of azathioprine in rheumatoid arthritis. Eur J Clin Pharmacol 9, 405–410 (1976). https://doi.org/10.1007/BF00606556

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