Summary
Rheumatoid arthritis is the most common form of severe inflammatory arthropathy affecting patients at a relatively early age. Although there are a number of drugs which significantly reduce pain and swelling, few alter the development of erosions and progression of joint destruction. A significant number of patients with rheumatoid arthritis develop this progressive disability and will require treatment with corticosteroids or immunosuppressive agents.
In this article the use of immunosuppressive drugs and corticosteroids in the treatment of aggressive rheumatoid arthritis is reviewed. Controlled clinical trials have shown that a number of these drugs can play a significant role in reducing pain and swelling and might possibly alter the disease course in rheumatoid arthritis. Side effects of these agents, including the potential for oncogenesis, still pose major problems in their long term use. The risks and benefits of immunosuppressive and corticosteroid drug therapy must be balanced in each patient to whom they are prescribed and reviewed at frequent intervals.
Similar content being viewed by others
References
Allison AC, Lee SW. Proinflammatory and catabolic effects of interleukin-1 and their antagonism by glucocorticoids. Variability in response to antirheumatic drugs. In Brooks PM & Day RD (Eds) Agents and Actions (Suppl.), in press, 1988
Amor B, Mery C. Chlorambucil in rheumatoid arthritis. Clinics in Rheumatic Diseases 6: 567–584, 1980
Anderson PA, West SG, O’Dell JR, Via CS, Claypool RG, et al. Weekly pulse methotrexate in rheumatoid arthritis: clinical and immunological effects in a randomised double blind study. Annals of Internal Medicine 103: 489–496, 1985
Anon. Cyclosporin in autoimmune disease. Lancet 1: 909–911, 1985
Aptekar RG, Atkinson JP, Decker JL, Wolff SM, Chu EW. Bladder toxicity with chronic oral cyclophosphamide therapy in non malignant disease. Arthritis and Rheumatism 16: 461–467, 1973
Austin HA, Klippel JM, Balow JE, Le Riche NGH, Steinberg AD, et al. Treatment of lupus nephritis: controlled trial of prednisone and cytotoxic drugs. New England Journal of Medicine 314: 614–619, 1986
Axelrod L. Glucocorticoids. In Kelly WN (Ed.) Textbook of rheumatology, pp. 815–832, Saunders, Philadelphia, 1985
Baker GL, Kahl LE, Lee BC, Stolzer BL, Agarwal AK, et al. Malignancy following treatment with cyclophosphamide: long term case-control follow-up study. American Journal of Medicine 83: 1–9, 1987
Balin PL, Tindall JP, Roenigk HH, Hogan MD. Is methotrexate therapy for psoriasis carcinogenic? A modified retrospective and prospective analysis. Journal of the American Medical Association 232: 359–362, 1975
Baltus JAM, Boersma JW, Hartman AP, Vandenbroucke JP. The occurrence of malignancies in patients with rheumatoid arthritis treated with cyclophosphamide: a controlled retrospective follow up. Annals of the Rheumatic Diseases 43: 368–373, 1983
Berg KJ, FørreØ, Bjerkhøel F, Amundsen E, Djøseland O, et al. Side effects of cyclosporin A treatment in patients with rheumatoid arthritis. Kidney International 29: 1180–1187, 1986
Bernstein CA, Freyberg RH. Rheumatoid patients after 5 or more years of corticosteroid treatment: a comparative analysis of 183 cases. Annals of Internal Medicine 54: 938–953, 1961
Berry H, Liyanage SP, Durance RA, Barnes GC, Berger LA, et al. Azathioprine and penicillamine in the treatment of rheumatoid arthritis: a controlled trial. British Medical Journal 1: 1052–1054, 1976
Bird H. The role of steroids in the treatment of arthritis: conference report. Annals of the Rheumatic Diseases 44: 642–643, 1985
Bitter T. Combined disease modifying chemotherapy for intractible rheumatoid arthritis. Clinics in Rheumatic Diseases 10: 417–428, 1984
Black RL, O’Brien W, Van Scott E, Averbach R, Eisen AZ, et al. Methotrexate therapy in psoriatic arthritis: double blind study on 21 patients. Journal of the American Medical Association 189: 743–747, 1964
Boardman PL, Hart FD. Clinical measurements of the anti-inflammatory effects of salicylates in rheumatoid arthritis. British Medical Journal 4: 264–268, 1967
Bontoux D, Kahan A, Brouilhet H, Amor B, Delbarre F. Effect and mode of action of chlorambucil in rheumatoid disease. Revue du Rhumatisme et des Maladies Ostéo-Articulaires 38: 759–764, 1971
Bookbinder SA, Espinoza LR, Fenske NA, Germaine BF, Vasey FB, et al. Methotrexate: its use in the rheumatic diseases. Clinical and Experimental Rheumatology 2: 185–193, 1984
Brooks PM, Kean W F, Buchanan WW. The clinical pharmacology of anti-inflammatory agents, pp. 123–134, Taylor and Francis, London, 1986
Butler D, Tiliakos N. Low dose cytotoxic drug combination therapy in intractible rheumatoid arthritis. Arthritis and Rheumatism 28: S15, 1985
Byron MA, Kirwan JR. Corticosteroids in rheumatoid arthritis: is a trial of their disease modifying potential feasible? Annals of the Rheumatic Diseases 46: 171–173, 1986
Calabresi P, Parks RE. Chemotherapy of neoplastic diseases. In Gilman AG & Goodman LS (Eds) The pharmacological basis of therapeutics, pp. 1249–1313, MacMillan, New York, 1970
Cannon GW, Jackson CG, Samuelson CO, Ward JR, Williams JM, et al. Chlorambucil therapy in rheumatoid arthritis: clinical experience in 28 patients and literature review. Seminars in Arthritis and Rheumatism 15: 106–118, 1985
Carson CW, Cannon GW, Egger MJ, Ward JR, Clegg DO, et al. Pulmonary disease during the treatment of rheumatoid arthritis with low dose pulse methotrexate. Seminars in Arthritis and Reheumatism 16: 186–195, 1987
Cayla J, Rondier J. The treatment of 67 cases of rheumatoid arthritis with chlorambucil drugs: with reference to 41 cases. Revue du Rhumatisme et des Maladies Ostéo-Articulaires 38: 771–774, 1971
Chanbe S, Krug G, Murphy ML. Teratogenic effects of cyclophosphamide in rats. Cancer Chemotherapy and Pharmacology 51: 363–367, 1971
Cobb S, Anderson F, Bauer W. Length of life and cause of death in rheumatoid arthritis. New England Journal of Medicine 249: 553–556, 1953
Cohen DJ, Loertscher R, Rubin MF, Tillney NL, Carpenter CB, et al. Cyclosporine: a new immunosuppressive agent for organ transplantation. Annals of Internal Medicine 101: 667–682, 1984
Conn HO, Blitzer BL. Non-association of adrenocorticosteroid therapy and peptic ulcer. New England Journal of Medicine 294: 471–479, 1976
Cooperating Clinics Committee of the American Rheumatism Association. A controlled trial of cyclophosphamide in rheumatoid arthritis. New England Journal of Medicine 283: 884–889, 1970
Cooperating Clinics Committee of the American Rheumatism Association. A controlled trial of high and low doses of cyclophosphamide in 82 patients with rheumatoid arthritis. Arthritis and Rheumatism 15: 434, 1972
Csuka ME, Carrera GF, McCarty DJ. Treatment of intractable rheumatoid arthritis with combined cyclophosphamide, azathioprine and hydroxychloroquine. Journal of the American Medical Association 255: 2315–2319, 1986
Cupps TR, Fauci AS. The vasculitides, pp. 155–172, WB-Saunders Co., Philadelphia, 1981
Currey HLF, Harris J, Mason M, Woodland J, Beveridge T, et al. Comparison of azathioprine, cyclophosphamide and gold in the treatment of rheumatoid arthritis. British Medical Journal 3: 763–766, 1974
Cushman P. Glucocorticoids and the gastrointestinal tract: current status. Gut 11: 534–539, 1970
Dalavanga YA, Detrick B, Hooks JJ, Dzosos AA, Moutsopoulos HM. Effect of cyclosporin A (Cy A) on the immunopathological lesion of the minor salivary glands from patients with Sjogren’s syndrome. Annals of the Rheumatic Diseases 46: 89–92, 1987
De Andrade JR, McCormick JN, Hill AGS. Small doses of prednisolone in the treatment of rheumatoid arthritis. Annals of the Rheumatic Diseases 24: 158–162, 1964
De Fronzo RA, Braine H, Colvin M, Davis PJ. Water intoxication in man after cyclophosphamide therapy: time course and relation to drug activation. Annals of Internal Medicine 78: 861–869, 1973
De Silva M, Hazleman BL. Long term azathioprine in rheumatoid arthritis: a double blind study. Annals of the Rheumatic Diseases 40: 560–563, 1981
Decker JL. Azathioprine and cyclophosphamide as slow acting drugs in rheumatoid arthritis. Journal of the American Medical Association 76: 74–78, 1983
Deodhar SD, Dick WC, Hodgkinson R, Buchanan WW. Measurement of clinical response to anti-inflammatory drug therapy in rheumatoid arthritis. Quarterly Journal of Medicine 42: 387–401, 1973
Deshayes P, Renier JC, Bregeon C, Houdent G. Incidents et accidents des théraputiques à visée immunodépressive dans la polyarthrite rheumatoide. Revue du Rhumatisme et des Maladies Ostéo-Articulaires 38: 797–806, 1971
Diaz A, Gonzalez B, Cortez J, Mintz G. A prospective study of methotrexate (MTX) and D-penicillamine (D-P) in rheumatoid arthritis (RA). Clinical and Experimental Rheumatology 5(S-2): 1231987
Dougados M, Amor B. Cyclosporin in rheumatoid arthritis. Arthritis and Rheumatism 28 (Suppl.): S36, 1985
Dougados M, Amor B. Cyclosporin A in rheumatoid arthritis: preliminary results of an open trial. Arthritis and Rheumatism 30: 83–87, 1987
Dougados M, Awada H, Amor B. Cyclosporin in rheumatoid arthritis: a double blind placebo controlled trial in 52 patients. Clinical and Experimental Rheumatology 5 (Suppl. 2): 124, 1987
Drosos AA, Skopoulis FN, Costopoulos JS, Papadimitriou CS, Moutsopoulos HM. Cyclosporin A (Cy A) in primary Sjogren’s syndrome: a double blind study. Annals of the Rheumatic Diseases 45: 732–735, 1986
Duggan CJ, Caterson RJ, Mahony JF, Boyce EF. Successful pregnancy in a renal transplant recipient taking cyclosporin A. Australian and New Zealand Journal of Medicine 16: 813–814, 1986
Dwosh IL, Stein HB, Urowitz MB, Smythe HA, Hunter T, et al. Azathioprine in early rheumatoid arthritis: comparison with gold and chloroquine. Arthritis and Rheumatism 20: 685–692, 1977
Edelman J, Russell AS, Biggs DF, Rothman RS, Coates J. Methotrexate levels, a guide to therapy? Clinical and Experimental Rheumatology 1: 153–156, 1983
Ejstrup L. Severe dermatomyositis treated with cyclosporin A. Annals of the Rheumatic Diseases 45: 612–613, 1986
Ellis CN, Gorsulowsky DC, Hamilton TA, Billings JR, Brown HD, et al. Cyclosporin improves psoriasis in a double blind study. Journal of the American Medical Association 256: 3110–3116, 1986
Empire Rheumatism Council. Multicentre controlled trial comparing cortisone acetate and acetylsalicylic acid in the long term treatment of rheumatoid arthritis. Annals of the Rheumatic Diseases 16: 277–289, 1957
Fairchild WV, Spence CR, Solomon HD, Gangai MP, et al. The incidence of bladder cancer after cyclophosphamide therapy. Journal of Urology 122: 163–164, 1979
Fitzcharles MA, Halsey J, Currey HLF. Conversion from daily to alternate daily corticosteroids in rheumatoid arthritis. Annals of the Rheumatic Diseases 41: 66–68, 1982
Fitzgerald O, Hanly J, Molony J, Bresnihan B. Poor longterm results from low dose methotrexate in rheumatoid arthritis. Arthritis and Rheumatism 27: 599–600, 1984
Flower RJ, Blackwell GJ. Antiinflammatory steroids induce synthesis of a phospholipase-A2 inhibitor which prevents prostaglandin generation. Nature 278: 456–459, 1979
Førre O, Bjerghoel F, Salvesen CF, et al. An open, controlled, randomised comparison of cyclosporin and azathioprine in the treatment of rheumatoid arthritis: a preliminary report. Arthritis and Rheumatism 30: 88–92, 1987
Fosdick WM, Parsons JL, Hill DF. Long term cyclophosphamide therapy in rheumatoid arthritis. Arthritis and Rheumatism 11: 151–161, 1968
Fosdick WM, Parsons JL, Hill DF. Long term cyclophosphamide therapy in rheumatoid arthritis: a progress report, six years’ experience. Arthritis and Rheumatism 12: 663, 1969
Furst DE. Clinical pharmacology of very low dose methotrexate for use in rheumatoid arthritis. Journal of Rheumatology 12 (Suppl. 12): 11–14, 1985
Gispen JG, Alarcon GS, Johnson JJ, Alton RT, et al. Toxicity to methotrexate in rheumatoid arthritis. Journal of Rheumatology 14: 74–79, 1987
Glick EN, Rigby P. Intra-articular use of triamcinolone hexacetonide. Arthritis and Rheumatism 14: 383–384, 1971
Gray RG, Tenenbaum TJ, Gottlieb NL. Local corticosteroid injection treatment in rheumatic disorders. Seminars in Arthritis and Rheumatism 10: 231–254, 1981
Griffiths CEM, Powles AV, Leonard JN, Fry L, Baker BS, et al. Clearance of psoriasis with low dose cyclosporin. British Medical Journal 293: 731–732, 1986
Groff GD, Shenberger FN, Wilke WS, Taylor TM. Low dose oral methotrexate in rheumatoid arthritis: an uncontrolled trial and review of the literature. Seminars in Arthritis and Rheumatism 12: 333–347, 1983
Gubner R, August S, Ginsberg V. Therapeutic suppression of tissue reactivity. II. Effect of aminopterin in rheumatoid arthritis and psoriasis. American Journal of the Medical Sciences 22: 176–182, 1951
Hall ND, Bird HA, Ring EFJ, Bacon PA. A combined clinical and immunological assessment of four cyclophosphamide regimens in rheumatoid arthritis. Agents and Actions 9: 97–102, 1979
Hamdy H, McKendry RJR, Merins E, Liver JA. Low dose methotrexate compared with azathioprine in the treatment of rheumatoid arthritis: a 24-week controlled clinical trial. Arthritis and Rheumatism 30: 361–368, 1987
Hansen TM, Dickmeiss E, Jans H, Hansen TI, Ingeman-Nielsen M, et al. Combination of methylprednisolone pulse therapy and remission inducing drugs in rheumatoid arthritis. Annals of the Rheumatic Diseases 46: 290–295, 1987
Harris ED, Emkey RD, Nicholas JE, Newberg A. Low dose prednisolone therapy in rheumatoid arthritis: a double blind study. Journal of Rheumatology 10: 713–721, 1983
Hartmann FA, Brownell KA, Hartmann WE. A further study of the hormone of the adrenal cortex. American Journal of Physiology 95: 670–680, 1930
Hatchuel R. Efficacité et mode d’action du Chlorambucil dans la polyarthrite rheumatoide. Étude controlée en double insu. À propos de 47 observations. Mémoire pour l’obtention du Certificat D’Études Speciales en Rheumatologie, Paris, 1972
Hench PS, Kendall EL, Slocumb CH, Polley HF. The effect of a hormone of the adrenal cortex (17-hydroxy-11 dehydroxycorticosterone; compound E), and of pituitary adrenocorticotropic hormone on rheumatoid arthritis: a preliminary report. Mayo Clinic Proceedings 24: 181–197, 1949
Herrman B, Muller W. Die therapie der chronischen polyarthritis mit cyclosporin A, einen nuen immunosuppressivum. Aktuelle Rheumatologie 4: 173–186, 1979
Hess EV, Kammen PL. Pulse therapy in rheumatoid arthritis. Annals of Internal Medicine 94: 128–129, 1981
Ho M, Wajszcuk A, Dummer JS, Starzl TE, Hakala TR. Infections in kidney, heart and liver transplant recipients on cyclosporin. Transplantation Proceedings 15: 2768–2774, 1983
Hoffmeister R. Methotrexate in rheumatoid arthritis. Arthritis and Rheumatism 15: 114, 1972
Hoffmeister RT. Methotrexate therapy in rheumatoid arthritis: 15 years experience. American Journal of Medicine 12: 69–73, 1983
Huffman DH, Wan SH, Azarnoff DL, et al. Pharmacokinetics of methotrexate. Clinical Pharmacology and Therapeutics 14: 572–579, 1973
Ianuzzi L, Dawson N, Zein N, Kushner I. Does drug therapy slow radiographic progression in rheumatoid arthritis? New England Journal of Medicine 303: 1023–1028, 1983
Isomaki J, Mutru O, Koota K. Death rate and causes of death in patients with rheumatoid arthritis. Scandinavian Journal of Rheumatology 4: 205–208, 1975
Jiminez-Diaz CJ, Garcia EL, Merchante A, Perianes J. Treatment of rheumatoid arthritis with nitrogen mustard: preliminary report. Journal of the American Medical Association 147: 1418–1419, 1951
Johns DG, Rutherford LD, Leighton PG, Vogel CL. Secretion of methotrexate into human milk. American Journal of Obstetrics and Gynecology 112: 978–980, 1972
Johnson WW, Meadows DC. Urinary bladder fibrosis and telangiectasia associated with long term cyclophosphamide therapy. New England Journal of Medicine 284: 290–294, 1971
Kahan BD, Reid M, Newburger J. Pharmacokinetics of cyclosporin in human renal transplantation. Transplant Proceedings 15: 446–453, 1983
Kahn MF, Arlet J, Bloch-Michel A, Canoit M, Chaovat Y, et al. 19 leucoses aigues après traitement des rhumatismes inflammatoires chronique et des connectivités par les agents cytolytiques à visée immunodepressive. Resultats d’une enquête rétrospective portant sur 2006 cas. Revue du Rhumatisme et des Maladies Ostéo-Articulaires 49: 163, 1979
Kahn MF, Bedoiseau M, de Seze S. Immunosuppressive drugs in the management of malignant and severe rheumatoid arthritis. Proceedings of the Royal Society of Medicine 60: 130–133, 1967
Kahn MF, Bedoiseau M, Six B, Le Goff P, de Seze S. Chlorambucil in rheumatoid arthritis. Revue du Rhumatisme et des Maladies Ostéo-Articulaires 38: 741–748, 1971
Karvosky J. Clinical pharmacology and toxicology of cyclophosphamide: emphasis on use in rheumatic disease. Seminars in Arthritis and Rheumatism 12: 359–372, 1983
Keown PA, Stiller CR, Laupacis AL, Howson W, Coles R, et al. The effects and side effects of cyclosporine: relationship to drug pharmacokinetics. Transplantation Proceedings 14: 36–45, 1982
Kinlen LJ. Incidence of cancer in rheumatoid arthritis and other disorders after immunosuppressive treatment. American Journal of Medicine 78 (Suppl. 1A): 44–49, 1985
Kremer JM, Galivan J, Strekfuss A, Kamen B. Methotrexate metabolism analysis in blood and liver of rheumatoid arthritis patients: association with hepatic folic acid deficiency and formation of polyglutamates. Arthritis and Rheumatism 29: 832–835, 1986
Kremer JM, Lee JK. The safety and efficacy of the use of methotrexate in long term therapy for rheumatoid arthritis. Arthritis and Rheumatism 29: 822–831, 1986
Lebranchu Y, Drucker J, Nivet H, Rolland JC, Grenier B, et al. Acute monoblastic leukaemia in a child receiving chlorambucil for juvenile rheumatoid arthritis. Lancet 1: 649, 1980
Lee P, Anderson JA, Miller J, Webb J, Buchanan WW. Evaluation of analgesic action and efficacy of antirheumatic drug. Journal of Rheumatology 3: 283–294, 1976
Leibling MR, Lieb E, McLaughlin K, Blocka K, Furst D, et al. A double blind crossover trial of methyl prednisolone pulse therapy in rheumatoid arthritis. Arthritis and Rheumatism 23: 711, 1980
Leibling MR, Lieb E, McLaughlin K, Blocka K, Furst DE, et al. Pulse methylprednisolone in rheumatoid arthritis: a double-blind crossover trial. Annals of Internal Medicine 94: 21–26, 1981
Levy J, Paulus HE. Comparison of azathioprine and cyclophosphamide in the treatment of rheumatoid arthritis. Arthritis and Rheumatism 18: 412–413, 1975
Levy J, Paulus HE, Bangert R. Comparison of azathioprine and cyclophosphamide in treatment of rheumatoid arthritis. Arthritis and Rheumatism 18: 412–417, 1975
Levy J, Paulus HE, Barnett EV, et al. A double blind controlled evaluation of azathioprine treatment in rheumatoid arthritis and psoriatic arthritis. Arthritis and Rheumatism 15: 116–117, 1972
Lewis GJ, Lamont CAR, Lee HA, Slapak M. Successful pregnancy in a renal transplant recipient taking cyclosporin A. British Medical Journal 286: 603, 1983
Lewis P, Hazleman BL, Hanka R, Roberts S. Cause of death in patients with rheumatoid arthritis treated with azathioprine. Annals of the Rheumatic Diseases 39: 457–461, 1980
Lidksy MD, Sharp JT, Billings S. Double blind study of cyclophophamide in rheumatoid arthritis. Arthritis and Rheumatism 16: 148–153, 1973
Lockie ML, Gomez E, Smith DM. Low dose adrenocorticoids in the management of elderly patients with rheumatoid arthritis: selected examples and summary of efficacy in the long term treatment of 97 patients. Seminars in Arthritis and Rheumatism 12: 373–382, 1983
MacKenzie AH. Liver biopsy findings after methotrexate therapy for rheumatoid arthritis. Journal of Rheumatology 1 (Suppl. 1): 73, 1974
MacKinnon S, Starkebaum G, Willkens RF. Pancytopenia associated with low dose pulse methotrexate in the treatment of rheumatoid arthritis. Seminars in Arthritis and Rheumatism 15: 119–126, 1985
Madhok R, Capell H. Cyclosporin A: a potential disease modifying drug in rheumatoid arthritis. Arthritis and Rheumatism 28 (Suppl.): S68, 1985
Mason M, Currey HLF, Barnes CG, Dunne JF, Hazleman BL, et al. Azathioprine in rheumatoid arthritis. British Medical Journal 1: 420–422, 1969
Medical Research Council and Nuffield Foundation on Clinical Trials. A comparison of cortisone and aspirin in the treatment of early cases of rheumatoid arthritis. British Medical Journal 1: 695–700, 1955
Meffin PJ, Brooks PM, Sallustio BC. Alterations in prednisolone disposition as a result of time of administration, gender and dose. British Journal of Clinical Pharmacology 17: 395–404, 1984
Miller III JJ, Williams GF, Leissring JG. Multiple late complications of cyclophosphamide, including ovarian destruction. American Journal of Medicine 50: 530–535, 1971
Millon R, Kellgren JH, Poole P, Jayson MIV. Long term study of management of rheumatoid arthritis. Lancet 1: 812–816, 1984
Mitchell DM, Spitz PW, Young DY, Bloch DA, McShane DJ, et al. Survival, prognosis and causes of death in rheumatoid arthritis. Arthritis and Rheumatism 29: 706–714, 1986
Müftüglu AU, Pazarli H, Yurdakul S, Yazici H, Ülkü BY, et al. Short term cyclosporin A treatment of Bechet’s disease. British Journal of Ophthalmology 71: 387–390, 1987
Myles AB, Daly JR. Effect of corticosteroids and adrenocorticotrophic hormone on the hypothalamo-pituitary-adrenal axis. In Corticosteroid and ACTH treatment, pp. 66–81, Arnold, London, 1974
Myles A. Corticosteroid treatment in rheumatoid arthritis. British Journal of Rheumatology 24: 125–127, 1985
Needs CJ, Smith M, Boutagy J, Donovan S, Cosh D, et al. Comparison of methylprednisolone (1 gram IV) with prednisolone (1 gram orally) in rheumatoid arthritis: a pharmacokinetic and clinical study. Journal of Rheumatology 15: 224–228, 1988
Neumann VC, Hopkins R, Dixon JS, Bird HA, Wright VA. Combination therapy with pulsed methylprednisolone in rheumatoid arthritis: alone or in combination. British Journal of Rheumatology 23: 118–119, 1984
Nolan GH, Sweet RL, Laros RF, Roure CA. Renal cadaver transplantation followed by successful pregnancies. Obstetrics and Gynecology 43: 732–739, 1974
Nordstrom DM, West SG, Anderson PA. Pulse methotrexate in rheumatoid arthritis: a controlled prospective roentenographic study. Annals of Internal Medicine 107: 797–801, 1987
Nussenblatt RB, Palestine AG, Chan CC, Mochizuki M, Yancey K. Effectiveness of cyclosporin therapy for Bechet’s disease. Arthritis and Rheumatism 28: 671–679, 1985
O’Callaghan JW, Brooks PM. Disease modifying agents and immunosuppressive drugs in the elderly. Clinics in Rheumatoid Diseases 12: 275–289, 1986
Palestine AG, Nussenblatt RB, Chan CC. Side effects of systemic cyclosporin in patients not undergoing transplantation. American Journal of Medicine 77: 652–656, 1984
Palmer RG, Varonos S, Dore CJ, Denman AM, Ansell BM. Chlorambucil induced chromosome damage in juvenile chronic arthritis. Archives of Disease in Childhood 60: 1008–1013, 1985
Paulus HE, Williams JH, Ward JR, Reading JC, Egger MJ, et al. Azathioprine versus d-penicillamine in rheumatoid arthritis patients who have been treated unsuccessfully with gold. Arthritis and Rheumatism 27: 721–727, 1984
Pickup ME. Clinical pharmacokinetics of prednisone and prednisolone. Clinical Pharmacokinetics 4: 111–128, 1979
Rasker JJ, Cosh JA. Cause and age at death in a prospective study of 100 patients with rheumatoid arthritis. Annals of the Rheumatic Diseases 40: 115–120, 1981
Reese LT, Grimsham JW, Aach RD, Eisen AZ. Effects of methotrexate on the liver in psoriasis. Journal of Investigative Dermatology 62: 597–602, 1974
Ritchie DM, Boyle JA, McInnes JM, Jasani MK, Dalakos TG, et al. Clinical studies with an articular index for the assessment of joint tenderness in patients with rheumatoid arthritis. Quarterly Journal of Medicine 37: 393–406, 1968
Sambrook PN, Eisman JA, Yeates MG, Pocock NA, Ebert S, et al. Osteoporosis in rheumatoid arthritis: safety of low dose corticosteroids. Annals of the Rheumatic Diseases 45: 950–953, 1986
Scherbel AL. Intravenous administration of nitrogen mustard alone and with corticotropin for rheumatoid arthritis. Cleveland Clinic Quarterly 24: 75–82, 1957
Schilsky RL, Lewis BJ, Sherins RJ, Young RC. Gonadal dysfunction in patients receiving chemotherapy for cancer. Annals of Internal Medicine 93: 109–114, 1980
Scott DGI, Bacon PA. Intravenous cyclophosphamide plus methylprednisolone in the treatment of systemic rheumatoid vasculitis. American Journal of Medicine 76: 77–85, 1984
Scott DL, Symmonds DPM, Coulton BL. Long term outcome of treating rheumatoid arthritis: results after 20 years. Lancet 1: 1108–1111, 1987
Settas L, Alexiou P, Mataftsi E, et al. Oral methotrexate in rheumatoid arthritis: a double blind crossover study. Clinical and Experimental Rheumatology 5 (Suppl. 2): 122, 1987
Skolal JE, Lessman EM. Effects of cancer chemotherapy on the human fetus. Journal of the American Medical Association 172: 1765–1767, 1960
Smyth CJ, Bartholomew BA, Mills DM, Steigerwald JC, Strong SJ, et al. Cyclophosphamide therapy for rheumatoid arthritis. Archives of Internal Medicine 135: 789–793, 1975
Sostman HD, Matthay RA, Putman CE. Methotrexate induced pneumonitis. Medicine 55: 371–388, 1976
St Clair EW, Ric JR, Snyderman R. Pneumonitis complicating low dose methotrexate therapy in rheumatoid arthritis. Archives of Internal Medicine 145: 2035–2038, 1985
Starzl TE, Nalesnick MA, Porter KA, Ho M, Iwatsuki S, et al. Reversibility of lymphoma and lymphoproliferative lesions developing under cyclosporin-steroid therapy. Lancet 1: 583–587, 1984
Swingle WW, Pfiffner JJ. Experiments with an active extract of the suprarenal cortex. Anatomical Record 44: 225–226, 1930a
Swingle WW, Pfiffner JJ. An aqueous extract of the suprarenal cortex which maintains the life of bilaterally adrenalectomised cats. Science 71: 321–322, 1930b
Tannenbaum H, Schur PH. Development of reticulum cell sarcoma during cyclophosphamide therapy. Arthritis and Rheumatism 17: 15–17, 1974
Thompson RN, Watts C, Edelman J, Esdaile J, Russel AS. A controlled two centre trial of parenteral methotrexate therapy for refractory rheumatoid arthritis. Journal of Rheumatology 11: 760–763, 1984
Thorpe P, Hassal JE, York JR. Rheumatoid arthritis treated with chlorambucil: a five year follow up. Medical Journal of Australia 2: 197–199, 1976
Tolman KG, Clegg DO, Lee RG, Ward JR. Methotrexate and the liver. Journal of Rheumatology 12 (Suppl. 12): 29–34, 1985
Townes AJ, Sowa JM, Shulman LE. Controlled trial of cyclophosphamide in rheumatoid arthritis. Arthritis and Rheumatism 19: 563–573, 1976
Tugwell P, Bennett K, Gent M. Methotrexate in rheumatoid arthritis: indications, contraindications, efficacy and safety. Annals of Internal Medicine 107: 358–366, 1987
Uddin J, Kraus AS, Kelly HG. Survivorship and death in rheumatoid arthritis. Arthritis and Rheumatism 13: 125–131, 1970
Urowitz MB, Gordon DA, Smythe HA, Prozanski W, Oeryzlo MA. Azathioprine in rheumatoid arthritis: a double-blind, crossover study. Arthritis and Rheumatism 16: 411–417, 1973
Urowitz MB, Hunter T, Bookman AAM, Gordon DA, Smythe HA, et al. Azathioprine in rheumatoid arthritis: a double blind study comparing full dose to half dose. Journal of Rheumatology 1: 274–281, 1974
Urowitz MB, Smythe HA, Able T, Norman CS, Travis C. Long term effects of azathioprine in rheumatoid arthritis. Annals of the Rheumatic Diseases 41 (Suppl.): 18–22, 1982
Van Rijthoven AWAM, Dijkmans BAC, Goei The HS, Hermans J, Montanor-Beckers ZLMB, et al. Cyclosporin treatment for rheumatoid arthritis: a placebo controlled, double blind, multi-centre study. Annals of the Rheumatic Diseases 45: 726–731, 1986
Vandermeer S, Imhoff JW, Borleffs JCC. Cyclosporin for polymyositis. Annals of the Rheumatic Diseases 45: 612, 1986
Warne GL, Fairley KF, Hobbs JB, Martin FIR. Cyclophosphamide induced ovarian failure. New England Journal of Medicine 289: 1159–1162, 1973
Weinblatt ME. Toxicity of low dose methotrexate in rheumatoid arthritis. Journal of Rheumatology 12 (Suppl. 12): 35–39, 1985
Weinblatt ME, Coblyn JS, Fox DA, Fraser PA, Holdsworth DE, et al. Efficacy of low dose methotrexate in rheumatoid arthritis. New England Journal of Medicine 312: 818–822, 1985
Weinblatt ME, Coblyn JS, Fraser PA, Anderson RJ, Spragg J, et al. Cyclosporin A treatment of refractory rheumatoid arthritis. Arthritis and Rheumatism 30: 11–17, 1987
Weinstein A, Bujac D. Methotrexate or gold in early rheumatoid arthritis: a double blind study. Clinical and Experimental Rheumatology (Suppl. 2): 122, 1987
Weiss RB, Muggia FM. Cytotoxic drug-induced pulmonary disease. American Journal of Medicine 68: 259–266, 1980
Williams HJ, Willkens RF, Samuelson CO, Alarcon GS, Guttadauria M, et al. Comparison of low dose oral pulse methotrexate and placebo in the treatment of rheumatoid arthritis: a controlled clinical trial. Arthritis and Rheumatism 28: 721–730, 1985
Williams IA, Bayliss EM, Shipley ME. A double blind placebo controlled trial of methyl prednisolone pulse therapy in active rheumatoid disease. Lancet 2: 2137–2140, 1982
Williams JH, Reading JC, Ward JR, O’Brien WM. Comparison of high and low dose cyclophosphamide therapy in rheumatoid arthritis. Arthritis and Rheumatism 23: 521–527, 1980
Willkens RF, Watson MA, Paxson CS. Low dose pulse methotrexate therapy in rheumatoid arthritis. Journal of Rheumatology 7: 501–505, 1980
Wood AJ, Maurer G, Niederberger W, Beveridge T. Cyclosporine: pharmacokinetics, metabolism and drug interactions. Transplantation Proceedings 15: 2409–2415, 1983
Woodland J, Chaput de Saintonge DM, Evans SJW, Sharman VL, Currey HLF. Azathioprine in rheumatoid arthritis: a double blind study of full versus half doses versus placebo. Annals of the Rheumatic Diseases 40: 355–359, 1981
Zachariae H, Grunnet E, Sogaard H. Liver biopsy in methotrexate treated psoriatics: a re-evaluation. Acta Dermato-Venereologica (Stockholm) 55: 291–296, 1975
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Arnold, M., Schrieber, L. & Brooks, P. Immunosuppressive Drugs and Corticosteroids in the Treatment of Rheumatoid Arthritis. Drugs 36, 340–363 (1988). https://doi.org/10.2165/00003495-198836030-00005
Published:
Issue Date:
DOI: https://doi.org/10.2165/00003495-198836030-00005