Advances in immunosuppressive therapy

Seminars in Respiratory and Critical Care Medicine

Volumn 28, Issue 4, 2007, Pages 398-417

  Marder, Wendy ^a   McCune, W Joseph ^a,b  

^a UNIVERSITY OF MICHIGAN MEDICAL SCHOOL   (United States)

^b UNIVERSITY OF MICHIGAN   (United States)

Author keywords

Cyclophosphamide; Mycophenolate mofetil; Sequential therapy; Wegener's granulomatosis

Indexed keywords

ACROLEIN; ADALIMUMAB; ALKYLATING AGENT; AMINOTRANSFERASE; AZATHIOPRINE; CHLORAMBUCIL; CHLORMETHINE; CORTICOSTEROID; COTRIMOXAZOLE; CYCLOPHOSPHAMIDE; CYCLOSPORIN A; DAPSONE; DISEASE MODIFYING ANTIRHEUMATIC DRUG; ETANERCEPT; FOLIC ACID; FOLINIC ACID; HOMOCYSTEINE; IMMUNOSUPPRESSIVE AGENT; INFLIXIMAB; LEFLUNOMIDE; LEUPRORELIN; MESNA; METHOTREXATE; METHYLPREDNISOLONE; MYCOPHENOLIC ACID 2 MORPHOLINOETHYL ESTER; PREDNISONE; SULFANILAMIDE DERIVATIVE; TERIFLUNOMIDE; TESTOSTERONE; THYMOCYTE ANTIBODY; UNINDEXED DRUG;

ABDOMINAL PAIN; ALOPECIA; AMENORRHEA; AMINOTRANSFERASE BLOOD LEVEL; ANCA ASSOCIATED VASCULITIS; ANENCEPHALUS; ANOREXIA; AZOOSPERMIA; BACTERIAL INFECTION; BEHCET DISEASE; BLADDER CANCER; BLADDER CARCINOMA; BLOOD TOXICITY; BONE MARROW SUPPRESSION; BONE MARROW TOXICITY; CONGENITAL HEART DISEASE; CONGENITAL MALFORMATION; CONTINUOUS INFUSION; CREATININE BLOOD LEVEL; CYTOPENIA; DIARRHEA; DISEASE ASSOCIATION; DISEASE SEVERITY; DRUG DOSE INCREASE; DRUG DOSE REDUCTION; DRUG DOSE TITRATION; DRUG EFFICACY; DRUG FATALITY; DRUG HYPERSENSITIVITY; DRUG MECHANISM; DRUG MEGADOSE; DRUG SUBSTITUTION; DRUG WITHDRAWAL; EARLY MENOPAUSE; FATTY LIVER; FIBROSING ALVEOLITIS; GASTROINTESTINAL MOTILITY DISORDER; GASTROINTESTINAL SYMPTOM; GASTROINTESTINAL TOXICITY; GIANT CELL ARTERITIS; GINGIVA HYPERPLASIA; GLOMERULUS FILTRATION RATE; GOUT; HEART DISEASE; HEMATOLOGIC MALIGNANCY; HEMATURIA; HEMORRHAGIC CYSTITIS; HEPATITIS; HERPES ZOSTER; HODGKIN DISEASE; HUMAN; HYDROCEPHALUS; HYPERTENSION; HYPERTRICHOSIS; HYPERURICEMIA; IMMUNOSUPPRESSIVE TREATMENT; INAPPROPRIATE VASOPRESSIN SECRETION; INFECTION; INFERTILITY; INTERSTITIAL LUNG DISEASE; INTERSTITIAL PNEUMONIA; KIDNEY DYSFUNCTION; KIDNEY TUBULE DAMAGE; LEUKOPENIA; LIVER CIRRHOSIS; LIVER FAILURE; LIVER FIBROSIS; LIVER HYPERTROPHY; LIVER TOXICITY; LIVER VENOOCCLUSIVE DISEASE; LOW BIRTH WEIGHT; LUNG FIBROSIS; LUNG INJURY; LUNG TOXICITY; LUPUS ERYTHEMATOSUS NEPHRITIS; LYMPHOMA; LYMPHOPROLIFERATIVE DISEASE; MACROCYTIC ANEMIA; MEGALOBLASTIC ANEMIA; MEGALOCYTOSIS; MICROCEPHALY; MICROSCOPIC POLYANGIITIS; MYELODYSPLASTIC SYNDROME; MYOSITIS; NAUSEA; NEPHROTOXICITY; NEUROTOXICITY; NEUTROPENIA; NONHODGKIN LYMPHOMA; NONHUMAN; OBSTRUCTIVE JAUNDICE; OPPORTUNISTIC INFECTION; OVARY INSUFFICIENCY; PANCREATITIS; PARESTHESIA; PNEUMOCYSTOSIS; PNEUMONIA; PREMATURE OVARIAN FAILURE; PREMATURITY; PRIORITY JOURNAL; PSORIATIC ARTHRITIS; REITER SYNDROME; REMISSION; REPRODUCTIVE TOXICITY; REVIEW; RHEUMATIC DISEASE; RHEUMATOID ARTHRITIS; SARCOIDOSIS; SCLERODERMA; SIDE EFFECT; SKIN CANCER; SOLID TUMOR; SPONTANEOUS ABORTION; SQUAMOUS CELL CARCINOMA; STOMATITIS; SYSTEMIC DISEASE; SYSTEMIC VASCULITIS; TERATOGENICITY; TRANSITIONAL CELL CARCINOMA; TREMOR; UREMIA; URINARY TRACT CANCER; UTERINE CERVIX CANCER; VASCULITIS; VOMITING; WEGENER GRANULOMATOSIS; WEIGHT REDUCTION; DOSE RESPONSE; DRUG COMBINATION;

ALKYLATING AGENTS; CYCLOPHOSPHAMIDE; DOSE-RESPONSE RELATIONSHIP, DRUG; DRUG THERAPY, COMBINATION; HUMANS; IMMUNOSUPPRESSIVE AGENTS; LUNG DISEASES, INTERSTITIAL; RHEUMATIC DISEASES;

EID: 35848929726     PISSN: 10693424     EISSN: None     Source Type: Journal    
DOI: 10.1055/s-2007-985612     Document Type: Review

References (205)

1. Walters MT, Cawley MI. Combined suppressive drug treatment in severe refractory rheumatoid disease: an analysis of the relative effects of parenteral methylprednisolone, cyclophosphamide, and sodium aurothiomalate. Ann Rheum Dis 1988;47:924-929
2. Cash JM, Klippel JH. Second-line drug therapy for rheumatoid arthritis. N Engl J Med 1994;330:1368-1375
3. Takada K, Arefayene M, Desta Z, et al. Cytochrome P450 pharmacogenetics as a predictor of toxicity and clinical response to pulse cyclophosphamide in lupus nephritis. Arthritis Rheum 2004;50:2202-2210
4. Turk JL, Poulter LW. Selective depletion of lymphoid tissue by cyclophosphamide. Clin Exp Immunol 1972;10: 285-296
5. Clements PJ, Yu DT, Levy J, et al. Effects of cyclophosphamide on B- and T-lymphocytes in rheumatoid arthritis. Arthritis Rheum 1974;17:347-353
6. Hurd ER, Giuliano VJ. The effect of cyclophosphamide on B and T lymphocytes in patients with connective tissue diseases. Arthritis Rheum 1975;18:67-75
7. McCune WJ, Golbus J, Zeldes W, et al. Clinical and immunologic effects of monthly administration of intravenous cyclophosphamide in severe systemic lupus erythematosus. N Engl J Med 1988;318:1423-1431
8. Chiorazzi N, Fox DA, Katz DH. Hapten-specific IgE antibody responses in mice, VI: Selective enhancement of IgE antibody production by low doses of x-irradiation and by cyclophosphamide. J Immunol 1976;117(5 Pt 1):1629-1637
9. Langford CA, Talar-Williams C, Barron KS, et al. A staged approach to the treatment of Wegener's granulomatosis: induction of remission with glucocorticoids and daily cyclophosphamide switching to methotrexate for remission maintenance. Arthritis Rheum 1999;42:2666-2673
10. Wegener's Granulomatosis Etanercept Trial (WGET) Research Group. Etanercept plus standard therapy for Wegener's granulomatosis. N Engl J Med 2005;352:351-361
11. McCarthy CJ, Sheldon S, Ross CW, et al. Cytogenetic abnormalities and therapy-related myelodysplastic syndromes in rheumatic disease. Arthritis Rheum 1998;41: 1493-1496
12. Malik SW, Myers JL, DeRemee RA, et al. Lung toxicity associated with cyclophosphamide use: two distinct patterns. Am J Respir Crit Care Med 1996;154(6 Pt 1):1851-1856
13. Mark GJ, Lehimgar-Zadeh A, Ragsdale BD. Cyclophosphamide pneumonitis. Thorax 1978;33:89-93
14. Zisman DA, McCune WJ, Tino G, et al. Drug-induced pneumonitis: the role of methotrexate. Sarcoidosis Vasc Diffuse Lung Dis 2001;18:243-252
15. Lynch JP III, Chavis AD. Chronic interstitial pulmonary disorders. In: Victor TC, ed. Clinical Pulmonary Disorders. Boston: Little, Brown; 1992:193-264
16. Myers JL. Diagnosis of drug reactions in the lung. Monogr Pathol 1993;36:32-53
17. Hoffman GS, Kerr GS, Leavitt RY, et al. Wegener granulomatosis: an analysis of 158 patients. Ann Intern Med 1992;116:488-498
18. Baker GL, Kahl LE, Zee BC, et al. Malignancy following treatment of rheumatoid arthritis with cyclophosphamide: long-term case-control follow-up study. Am J Med 1987; 83:1-9
19. Talar-Williams C, Hijazi YM, Walther MM, et al. Cyclophosphamide-induced cystitis and bladder cancer in patients with Wegener granulomatosis. Ann Intern Med 1996;124:477-484
20. Travis LB, Curtis RE, Glimelius B, et al. Bladder and kidney cancer following cyclophosphamide therapy for non-Hodgkin's lymphoma. J Natl Cancer Inst 1995;87:524-530
21. Fox DA, McCune WJ. Immunologic and clinical effects of cytotoxic drugs used in the treatment of rheumatoid arthritis and systemic lupus erythematosus. Concepts Immunopathol 1989;7:20-78
22. Radis CD, Kahl LE, Baker GL, et al. Effects of cyclophosphamide on the development of malignancy and on long-term survival of patients with rheumatoid arthritis: a 20-year follow-up study. Arthritis Rheum 1995;38:1120-1127
23. Ognenovski VM, Marder W, Somers EC, et al. Increased incidence of cervical intraepithelial neoplasia in women with systemic lupus erythematosus treated with intravenous cyclophosphamide. J Rheumatol 2004;31:1763-1767
24. Lynch JP III, McCune WJ. Immunosuppressive and cytotoxic pharmacotherapy for pulmonary disorders. Am J Respir Crit Care Med 1997;155:395-420
25. Stone JH, Holbrook JT, Marriott MA, et al. Solid malignancies among patients in the Wegener's Granulomatosis Etanercept Trial. Arthritis Rheum 2006;54:1608-1618
26. Koyama H, Wada T, Nishizawa Y, et al. Cyclophosphamide-induced ovarian failure and its therapeutic significance in patients with breast cancer. Cancer 1977;39(4):1403-1409
27. Boumpas DT, Chrousos GP, Wilder RL, et al. Glucocorticoid therapy for immune-mediated diseases: basic and clinical correlates. Ann Intern Med 1993;119:1198-1208
28. Blumenfeld Z. Ovarian rescue/protection from chemotherapeutic agents. J Soc Gynecol Investig 2001;8(1 Suppl Proceedings):S60-S64
29. Blumenfeld Z, Shapiro D, Shteinberg M, et al. Preservation of fertility and ovarian function and minimizing gonadotoxicity in young women with systemic lupus erythematosus treated by chemotherapy. Lupus 2000;9: 401-405
30. Pereyra Pacheco B, Mendez Ribas JM, Milone G, et al. Use of GnRH analogs for functional protection of the ovary and preservation of fertility during cancer treatment in adolescents: a preliminary report. Gynecol Oncol 2001;81:391-397
31. Somers EC, Marder W, Christman GM, et al. Use of a gonadotropin-releasing hormone analog for protection against premature ovarian failure during cyclophosphamide therapy in women with severe lupus. Arthritis Rheum 2005;52:2761-2767
32. Hoorweg-Nijman JJ, Delemarre-van de Waal HA, de Waal FC, et al. Cyclophosphamide-induced disturbance of gonadotropin secretion manifesting testicular damage. Acta Endocrinol (Copenh) 1992;126:143-148
33. Masala A, Faedda R, Alagna S, et al. Use of testosterone to prevent cyclophosphamide-induced azoospermia. Ann Intern Med 1997;126:292-295
34. Huynh-Do U, Gantenbein H, Binswanger U. Pneumocystis carinii pneumonia during immunosuppressive therapy for antineutrophil cytoplasmic autoantibody-positive vasculitis. Arch Intern Med 1995;155:872-874
35. Bradley JD, Brandt KD, Katz BP. Infectious complications of cyclophosphamide treatment for vasculitis. Arthritis Rheum 1989;32:45-53
36. de Groot K, Adu D, Savage CO. The value of pulse cyclophosphamide in ANCA-associated vasculitis: meta-analysis and critical review. Nephrol Dial Transplant 2001; 16:2018-2027
37. Mitrovic D, Popovic M, Stefanovic D, et al. Immunosuppressive therapy with cyclophosphamide pulse doses in Wegener's granulomatosis. Transplant Proc 2001;33:2378-2379
38. Contreras G, Pardo V, Leclercq B, et al. Sequential therapies for proliferative lupus nephritis. N Engl J Med 2004;350:971-980
39. Tashkin DP, Elashoff R, Clements PJ, et al. Cyclophosphamide versus placebo in scleroderma lung disease. N Engl J Med 2006;354:2655-2666
40. Flaherty KR, Martinez FJ. Nonspecific interstitial pneumonia. Semin Respir Crit Care Med 2006;27:652-658
41. Beretta L, Caronni M, Raimondi M, et al. Oral cyclophosphamide improves pulmonary function in scleroderma patients with fibrosing alveolitis: experience in one centre. Clin Rheumatol 2007;26:168-172
42. Lunseth JH, Baker LA, Shifrin A. Chronic scleroderma with acute exacerbation during corticotropin therapy, report of a case with autopsy observations. AMA Arch Intern Med 1951;88:783-792
43. Sharnoff JG, Carideo HL, Stein ID. Cortisone-treated scleroderma; report of a case with autopsy findings. J Am Med Assoc 1951;145:1230-1232
44. Steen VD, Medsger TA Jr. Case-control study of corticosteroids and other drugs that either precipitate or protect from the development of scleroderma renal crisis. Arthritis Rheum 1998;41:1613-1619
45. DeMarco PJ, Weisman MH, Seibold JR, et al. Predictors and outcomes of scleroderma renal crisis: the high-dose versus low-dose D-penicillamine in early diffuse systemic sclerosis trial. Arthritis Rheum 2002;46:2983-2989
46. Hoyles RK, Ellis RW, Wellsbury J, et al. A multicenter, prospective, randomized, double-blind, placebo-controlled trial of corticosteroids and intravenous cyclophosphamide followed by oral azathioprine for the treatment of pulmonary fibrosis in scleroderma. Arthritis Rheum 2006; 54:3962-3970
47. Yiannopoulos G, Pastromas V, Antonopoulos I, et al. Combination of intravenous pulses of cyclophosphamide and methylprednisolone in patients with systemic sclerosis and interstitial lung disease. Rheumatol Int 2007;27:357-361
48. Lehman TJ, Edelheit BS, Onel KB. Combined intravenous methotrexate and cyclophosphamide for refractory childhood lupus nephritis. Ann Rheum Dis 2004;63:321-323
49. Burt RK, Traynor AE. SLE: hematopoietic stem cell transplantation for systemic lupus erythematosus. Arthritis Res Ther 2003;5:207-209
50. Petri M, Jones RJ, Brodsky RA. High-dose cyclophosphamide without stem cell transplantation in systemic lupus erythematosus. Arthritis Rheum 2003;48:166-173
51. Langford CA, Talar-Williams C, Barron KS, et al. Use of a cyclophosphamide-induction methotrexate-maintenance regimen for the treatment of Wegener's granulomatosis: extended follow-up and rate of relapse. Am J Med 2003; 114:463-469
52. Jayne D, Rasmussen N, Andrassy K, et al. A randomized trial of maintenance therapy for vasculitis associated with antineutrophil cytoplasmic autoantibodies. N Engl J Med 2003;349:36-44
53. Slot MC, Tervaert JW, Boomsma MM, et al. Positive classic antineutrophil cytoplasmic antibody (C-ANCA) titer at switch to azathioprine therapy associated with relapse in proteinase 3-related vasculitis. Arthritis Rheum 2004;51: 269-273
54. Langford CA, Talar-Williams C, Sneller MC. Mycophenolate mofetil for remission maintenance in the treatment of Wegener's granulomatosis. Arthritis Rheum 2004;51:278-283
55. Metzler C, Fink C, Lamprecht P, et al. Maintenance of remission with leflunomide in Wegener's granulomatosis. Rheumatology (Oxford) 2004;43:315-320
56. Houssiau FA, Vasconcelos C, D'Cruz D, et al. Immunosuppressive therapy in lupus nephritis: the Euro-Lupus Nephritis Trial, a randomized trial of low-dose versus high-dose intravenous cyclophosphamide. Arthritis Rheum 2002; 46:2121-2131
57. Ginzler EM, Dooley MA, Aranow C, et al. Mycophenolate mofetil or intravenous cyclophosphamide for lupus nephritis. N Engl J Med 2005;353:2219-2228
58. Tessler HH, Jennings T. High-dose short-term chlorambucil for intractable sympathetic ophthalmia and Behçet's disease. Br J Ophthalmol 1990;74:353-357
59. Furst DE, Clements PJ, Hillis S, et al. Immunosuppression with chlorambucil, versus placebo, for scleroderma: results of a three-year, parallel, randomized, double-blind study. Arthritis Rheum 1989;32:584-593
60. Clements P, Lachenbruch P, Furst D, et al. The course of skin involvement in systemic sclerosis over three years in a trial of chlorambucil versus placebo. Arthritis Rheum 1993; 36:1575-1579
61. Cannon GW, Jackson CG, Samuelson CO Jr, et al. Chlorambucil therapy in rheumatoid arthritis: clinical experience in 28 patients and literature review. Semin Arthritis Rheum 1985;15:106-118
62. Kataria YP. Chlorambucil in sarcoidosis. Chest 1980;78:36-43
63. Sinoway PA, Callen JP. Chlorambucil. An effective corticosteroid-sparing agent for patients with recalcitrant dermatomyositis. Arthritis Rheum 1993;36:319-324
64. Steinberg AD. Chlorambucil in the treatment of patients with immune-mediated rheumatic diseases. Arthritis Rheum 1993;36:325-328
65. Kaklamani VG, Kaklamanis PG. Treatment of Behçet's disease: an update. Semin Arthritis Rheum 2001;30:299-312
66. Fauci AS, Haynes BF, Katz P, et al. Wegener's granulomatosis: prospective clinical and therapeutic experience with 85 patients for 21 years. Ann Intern Med 1983;98:76-85
67. Starzl TE, Marchioro TL, Dickinson TC, et al. Technique of renal homotransplantation: experience with 42 Cases. Arch Surg 1964;89:87-104
68. Lennard L, Van Loon JA, Weinshilboum RM. Pharmacogenetics of acute azathioprine toxicity: relationship to thiopurine methyltransferase genetic polymorphism. Clin Pharmacol Ther 1989;46:149-154
69. American College of Rheumatology Subcommittee on Rheumatoid Arthritis Guidelines. Guidelines for the management of rheumatoid arthritis: 2002 Update. Arthritis Rheum 2002;46:328-346
70. Benenson E, Fries JW, Heilig B, et al. High-dose azathioprine pulse therapy as a new treatment option in patients with active Wegener's granulomatosis and lupus nephritis refractory or intolerant to cyclophosphamide. Clin Rheumatol 2005;24:251-257
71. Pickenpack A, Straub RH, Distler O, et al. Safety and efficacy of an intravenous loading dose of azathioprine for treatment of non-TPMT-deficient patients with rheumatic diseases. Rheumatology (Oxford) 2000;39:1435-1436
72. Present DH, Meltzer SJ, Krumholz MP, et al. 6-Mercaptopurine in the management of inflammatory bowel disease: short- and long-term toxicity. Ann Intern Med 1989;111:641-649
73. Sterneck M, Wiesner R, Ascher N, et al. Azathioprine hepatotoxicity after liver transplantation. Hepatology 1991; 14:806-810
74. Bottomley WW, Ford G, Cunliffe WJ, et al. Aggressive squamous cell carcinomas developing in patients receiving long-term azathioprine. Br J Dermatol 1995;133:460-462
75. Smith JL, Wilkinson AH, Hunsicker LG, et al. Increased frequency of posttransplant lymphomas in patients treated with cyclosporin, azathioprine, and prednisone. Transplant Proc 1989;21(1 Pt 3):3199-3200
76. Silman AJ, Petrie J, Hazleman B, et al. Lymphoproliferative cancer and other malignancy in patients with rheumatoid arthritis treated with azathioprine: a 20 year follow up study. Ann Rheum Dis 1988;47:988-992
77. Nero P, Rahman A, Isenberg DA. Does long term treatment with azathioprine predispose to malignancy and death in patients with systemic lupus erythematosus? Ann Rheum Dis 2004:63:325-326
78. Fraser AG, Orchard TR, Robinson EM, et al. Long-term risk of malignancy after treatment of inflammatory bowel disease with azathioprine. Aliment Pharmacol Ther 2002; 16:1225-1232
79. Matalon ST, Ornoy A, Lishner M. Review of the potential effects of three commonly used antineoplastic and immunosuppressive drugs (cyclophosphamide, azathioprine, doxorubicin on the embryo and placenta). Reprod Toxicol 2004;18:219-230
80. Norgard B, Pedersen L, Fonager K, et al. Azathioprine, mercaptopurine and birth outcome: a population-based cohort study. Aliment Pharmacol Ther 2003;17:827-834
81. Polifka JE, Friedman JM. Teratogen update: azathioprine and 6-mercaptopurine. Teratology 2002;65:240-261
82. Norgard B, Pedersen L, Jacobsen J, et al. The risk of congenital abnormalities in children fathered by men treated with azathioprine or mercaptopurine before conception. Aliment Pharmacol Ther 2004;19:679-685
83. Janssen NM, Genta MS. The effects of immunosuppressive and anti-inflammatory medications on fertility, pregnancy, and lactation. Arch Intern Med 2000;160:610-619
84. Du Vivier A, Munro DD, Verbov J. Treatment of psoriasis with azathioprine. BMJ 1974;1:49-51
85. Calin A. A placebo controlled, crossover study of azathioprine in Reiter's syndrome. Ann Rheum Dis 1986;45:653-655
86. Muller-Quernheim J, Kienast K, Held M, et al. Treatment of chronic sarcoidosis with an azathioprine/prednisolone regimen. Eur Respir J 1999;14:1117-1122
87. Pacheco Y, Marechal C, Marechal F, et al. Azathioprine treatment of chronic pulmonary sarcoidosis. Sarcoidosis 1985;2:107-113
88. Raghu G, Depaso WJ, Cain K, et al. Azathioprine combined with prednisone in the treatment of idiopathic pulmonary fibrosis: a prospective double-blind, randomized, placebo-controlled clinical trial. Am Rev Respir Dis 1991;144:291-296
89. Yazici H, Pazarli H, Barnes CG, et al. A controlled trial of azathioprine in Behçet's syndrome. N Engl J Med 1990; 322:281-285
90. Lee JC, Gladman DD, Schentag CT, et al. The long-term use of azathioprine in patients with psoriatic arthritis. J Clin Rheumatol 2001;7:160-165
91. Dean T, Dewey A, Bara A, et al. Azathioprine as an oral corticosteroid sparing agent for asthma. Cochrane Database Syst Rev 2004;(1):CD003270
92. Esdaile JM, Joseph L, MacKenzie T, et al. The benefit of early treatment with immunosuppressive drugs in lupus nephritis. J Rheumatol 1995;22:1211
93. Austin HA III, Klippel JH, Balow JE, et al. Therapy of lupus nephritis: controlled trial of prednisone and cytotoxic drugs. N Engl J Med 1986;314:614-619
94. Winterbauer RH, Hammar SP, Hallman KO, et al. Diffuse interstitial pneumonitis: clinicopathologic correlations in 20 patients treated with prednisone/azathioprine. Am J Med 1978;65:661-672
95. Meier-Sydow J, Rust M, Kronenberger H, et al. Long-term follow-up of lung function parameters in patients with idiopathic pulmonary fibrosis treated with prednisone and azathioprine or d-penicillamine [in German]. Prax Klin Pneumol 1979;33(Suppl 1):680-688
96. Weese WC, Levine BW, Kazemi H. Interstitial lung disease resistant to corticosteroid therapy: report of three cases treated with azathioprine or cyclophosphamide. Chest 1975;67:57-60
97. Dheda K, Lalloo UG, Cassim B, et al. Experience with azathioprine in systemic sclerosis associated with interstitial lung disease. Clin Rheumatol 2004;23:306-309
98. Khanna D, Wu H, Park G, et al. Association of tumor necrosis factor alpha polymorphism, but not the shared epitope, with increased radiographic progression in a seropositive rheumatoid arthritis inception cohort. Arthritis Rheum 2006;54:1105-1116
99. Ortiz Z, Shea B, Suarez Almazor M, et al. Folic acid and folinic acid for reducing side effects in patients receiving methotrexate for rheumatoid arthritis. Cochrane Database Syst Rev 2000;(2):CD000951
100. Ortiz Z, Shea B, Suarez-Almazor ME, et al. The efficacy of folic acid and folinic acid in reducing methotrexate gastrointestinal toxicity in rheumatoid arthritis: a meta-analysis of randomized controlled trials. J Rheumatol 1998;25:36-43
101. Fox DA, McCune WJ. Immunosuppressive drug therapy of systemic lupus erythematosus. Rheum Dis Clin North Am 1994;20:265-299
102. Weinblatt ME. Methotrexate for chronic diseases in adults. N Engl J Med 1995;332:330-331
103. Chan ES, Cronstein BN. Molecular action of methotrexate in inflammatory diseases. Arthritis Res 2002;4:266-273
104. Genestier L, Paillot R, Fournel S, et al. Immunosuppressive properties of methotrexate: apoptosis and clonal deletion of activated peripheral T cells. J Clin Invest 1998;102:322-328
105. Rosengren S, Arfors KE, Proctor KG. Potentiation of leukotriene B4-mediated inflammatory response by the adenosine antagonist, 8-phenyl theophylline. Int J Microcirc Clin Exp 1991;10:345-357
106. Lewis JH, Schiff E. Methotrexate-induced chronic liver injury: guidelines for detection and prevention. The ACG Committee on FDA-related matters. American College of Gastroenterology. Am J Gastroenterol 1988;83:1337-1345
107. Weinblatt ME, Fraser P. Elevated mean corpuscular volume as a predictor of hematologic toxicity due to methotrexate therapy. Arthritis Rheum 1989;32:1592-1596
108. Mielants H, Veys EM, Van der Straeten C, et al. The efficacy and toxicity of a constant low dose of methotrexate as a treatment for intractable rheumatoid arthritis: an open prospective study. J Rheumatol 1991;18:978-983
109. Hilsden RJ, Urbanski SJ, Swain MG. End-stage liver disease developing with the use of methotrexate in heterozygous alpha 1-antitrypsin deficiency. Arthritis Rheum 1995;38:1014-1018
110. Kremer JM, Alarcon GS, Lightfoot RW Jr, et al. Methotrexate for rheumatoid arthritis: suggested guidelines for monitoring liver toxicity. American College of Rheumatology. Arthritis Rheum 1994;37:316-328
111. Cannon GW, Ward JR, Clegg DO, et al. Acute lung disease associated with low-dose pulse methotrexate therapy in patients with rheumatoid arthritis. Arthritis Rheum 1983;26:1269-1274
112. Imokawa S, Colby TV, Leslie KO, et al. Methotrexate pneumonitis: review of the literature and histopathological findings in nine patients. Eur Respir J 2000;15:373-381
113. Kremer JM, Alarcon GS, Weinblatt ME, et al. Clinical, laboratory, radiographic, and histopathologic features of methotrexate-associated lung injury in patients with rheumatoid arthritis: a multicenter study with literature review. Arthritis Rheum 1997;40:1829-1837
114. Cottin V, Tebib J, Massonnet B, et al. Pulmonary function in patients receiving long-term low-dose methotrexate. Chest 1996;109:933-938
115. Carroll GJ, Thomas R, Phatouros CC, et al. Incidence, prevalence and possible risk factors for pneumonitis in patients with rheumatoid arthritis receiving methotrexate. J Rheumatol 1994;21:51-54
116. Hargreaves MR, Mowat AG, Benson MK. Acute pneumonitis associated with low dose methotrexate treatment for rheumatoid arthritis: report of five cases and review of published reports. Thorax 1992;47:628-633
117. Padley SP, Adler B, Hansell DM, et al. High-resolution computed tomography of drug-induced lung disease. Clin Radiol 1992;46:232-236
118. Arakawa H, Yamasaki M, Kurihara Y, et al. Methotrexate-induced pulmonary injury: serial CT findings. J Thorac Imaging 2003;18:231-236
119. White DA, Rankin JA, Stover DE, et al. Methotrexate pneumonitis: bronchoalveolar lavage findings suggest an immunologic disorder. Am Rev Respir Dis 1989;139:18-21
120. Schnabel A, Richter C, Bauerfeind S, et al. Bronchoalveolar lavage cell profile in methotrexate induced pneumonitis. Thorax 1997;52:377-379
121. Gridley G, McLaughlin JK, Ekbom A, et al. Incidence of cancer among patients with rheumatoid arthritis. J Natl Cancer Inst 1993;85:307-311
122. Symmons DP. Neoplasms of the immune system in rheumatoid arthritis. Am J Med 1985;78(1A):22-28
123. Prior P. Cancer and rheumatoid arthritis: epidemiologic considerations. Am J Med 1985;78(1A):15-21
124. Thomas E, Brewster DH, Black RJ, et al. Risk of malignancy among patients with rheumatic conditions. Int J Cancer 2000;88:497-502
125. Ellman MH, Hurwitz H, Thomas C, et al. Lymphoma developing in a patient with rheumatoid arthritis taking low dose weekly methotrexate. J Rheumatol 1991;18:1741-1743
126. Mariette X, Cazals-Hatem D, Warszawki J, et al. Lymphomas in rheumatoid arthritis patients treated with methotrexate: a 3-year prospective study in France. Blood 2002;99:3909-3915
127. Balandraud N, Roudier J, Roudier C. What are the links between Epstein-Barr virus, lymphoma, and tumor necrosis factor antagonism in rheumatoid arthritis? Semin Arthritis Rheum 2005;34(5 Suppl 1):31-33
128. Kingsmore SF, Hall BD, Allen NB, et al. Association of methotrexate, rheumatoid arthritis and lymphoma: report of 2 cases and literature review. J Rheumatol 1992;19:1462-1465
129. Hoshida Y, Aozasa K. Malignancies in organ transplant recipients. Pathol Int 2004;54:649-658
130. Nalesnik MA, Jaffe R, Starzl TE, et al. The pathology of posttransplant lymphoproliferative disorders occurring in the setting of cyclosporine A-prednisone immunosuppression. Am J Pathol 1988;133:173-192
131. Hoshida Y, Xu JX, Fujita S, et al. Lymphoproliferative disorders in rheumatoid arthritis: clinicopathological analysis of 76 cases in relation to methotrexate medication. J Rheumatol 2007;34:322-331
132. Menke DM, Griesser H, Moder KG, et al. Lymphomas in patients with connective tissue disease: comparison of p53 protein expression and latent EBV infection in patients immunosuppressed and not immunosuppressed with methotrexate. Am J Clin Pathol 2000;113:212-218
133. Patsner B, Kenigsberg D. Successful treatment of persistent ectopic pregnancy with oral methotrexate therapy. Fertil Steril 1988;50:982-983
134. Hoffman GS, Leavitt RY, Kerr GS, et al. Treatment of glucocorticoid- resistant or relapsing Takayasu arteritis with methotrexate. Arthritis Rheum 1994;37:578-582
135. Langford CA, Talar-Williams C, Sneller MC. Use of methotrexate and glucocorticoids in the treatment of Wegener's granulomatosis: long-term renal outcome in patients with glomerulonephritis. Arthritis Rheum 2000; 43:1836-1840
136. Davies H, Olson L, Gibson P. Methotrexate as a steroid sparing agent for asthma in adults. Cochrane Database Syst Rev 2000;(2):CD000391
137. de Groot K, Muhler M, Reinhold-Keller E, et al. Induction of remission in Wegener's granulomatosis with low dose methotrexate. J Rheumatol 1998;25:492-495
138. Baughman RP, Winget DB, Lower EE. Methotrexate is steroid sparing in acute sarcoidosis: results of a double blind, randomized trial. Sarcoidosis Vasc Diffuse Lung Dis 2000;17:60-66
139. Douglas WW, Tazelaar HD, Hartman TE, et al. Polymyositis-dermatomyositis- associated interstitial lung disease. Am J Respir Crit Care Med 2001;164:1182-1185
140. Briemberg HR, Amato AA. Dermatomyositis and polymyositis. Curr Treat Options Neurol 2003;5:349-356
141. Hochberg MC, Feldman D, Stevens MB, et al. Antibody to Jo-1 in polymyositis/dermatomyositis: association with interstitial pulmonary disease. J Rheumatol 1984;11:663-665
142. Brazelton TR, Morris RE. Molecular mechanisms of action of new xenobiotic immunosuppressive drags: tacrolimus (FK506), sirolimus (rapamycin), mycophenolate mofetil and leflunomide. Curr Opin Immunol 1996;8:710-720
143. Palmer G, Burger D, Mezin F, et al. The active metabolite of leflunomide, A77 1726, increases the production of IL-1 receptor antagonist in human synovial fibroblasts and articular chondrocytes. Arthritis Res Ther 2004;6:R181-R189
144. Bartlett RR, Brendel S, Zielinski T, et al. Leflunomide, an immunorestoring drug for the therapy of autoimmune disorders, especially rheumatoid arthritis. Transplant Proc 1996;28:3074-3078
145. John GT, Manivannan J, Chandy S, et al. Leflunomide therapy for cytomegalovirus disease in renal allograft recipients. Transplantation 2004;77:1460-1461
146. Scott DL, Smolen JS, Kalden JR, et al. Treatment of active rheumatoid arthritis with leflunomide: two year follow-up of a double-blind, placebo-controlled trial versus sulfasalazine. Ann Rheum Dis 2001;60:913-923
147. Ginzler EMAC, Buyon J, Dooley MA, et al. A multicenter study of mycophenolate mofetil (MMF) vs. intravenous cyclophosphamide (IVC) as induction therapy for severe lupus nephritis (LN). N Engl J Med 2005;353:2219-2228
148. Siva C, Eisen SA, Shepherd R, et al. Leflunomide use during the first 33 months after food and drug administration approval: experience with a national cohort of 3,325 patients. Arthritis Rheum 2003;49:745-751
149. Smolen JS, Kalden JR, Scott DL, et al. Efficacy and safety of leflunomide compared with placebo and sulphasalazine in active rheumatoid arthritis: a double-blind, randomised, multicentre trial. European Leflunomide Study Group. Lancet 1999;353:259-266
150. McCurry J. Japan deaths spark concerns over arthritis drug. Lancet 2004;363:461
151. Sakai F, Noma S, Kurihara Y, et al. Leflunomide-related lung injury in patients with rheumatoid arthritis: imaging features. Mod Rheumatol 2005;15:173-179
152. Savage RL, Highton J, Boyd IW, et al. Pneumonitis associated with leflunomide: a profile of New Zealand and Australian reports. Intern Med J 2006;36:162-169
153. Suissa S, Hudson M, Ernst P. Leflunomide use and the risk of interstitial lung disease in rheumatoid arthritis. Arthritis Rheum 2006;54:1435-1439
154. Cohen SB, Iqbal I. Leflunomide. Int J Clin Pract 2003; 57:115-120
155. Strand V, Cohen S, Schiff M, et al. Treatment of active rheumatoid arthritis with leflunomide compared with placebo and methotrexate. Leflunomide Rheumatoid Arthritis Investigators Group. Arch Intern Med 1999;159: 2542-2550
156. Baughman RP, Lower EE. Leflunomide for chronic sarcoidosis. Sarcoidosis Vasc Diffuse Lung Dis 2004;21: 43-48
157. Sintchak MD, Nimmesgern E. The structure of inosine 5′- monophosphate dehydrogenase and the design of novel inhibitors. Immunopharmacology 2000;47:163-184
158. Allison AC, Eugui EM. Mycophenolate mofetil and its mechanisms of action. Immunopharmacology 2000;47:85-118
159. Senda M, DeLustro B, Eugui E, et al. Mycophenolic acid, an inhibitor of IMP dehydrogenase that is also an immunosuppressive agent, suppresses the cytokine-induced nitric oxide production in mouse and rat vascular endothelial cells. Transplantation 1995;60:1143-1148
160. Allison AC, Eugui EM. The design and development of an immunosuppressive drug, mycophenolate mofetil. Springer Semin Immunopathol 1993;14:353-380
161. Penny MJ, Boyd RA, Hall BM. Mycophenolate mofetil prevents the induction of active Heymann nephritis: association with Th2 cytokine inhibition. J Am Soc Nephrol 1998;9:2272-2282
162. Lipsky JJ. Mycophenolate mofetil. Lancet 1996;348:1357-1359
163. McCune WJ, Riskalla MM. Mycophenolate mofetil: a magic bullet for lupus? J Rheumatol 2005;32:967-970
164. McCune WJ. Mycophenolate mofetil for lupus nephritis. N Engl J Med 2005;353:2282-2284
165. Riskalla MM, Somers EC, Fatica RA, et al. Tolerability of mycophenolate mofetil in patients with systemic lupus erythematosus. J Rheumatol 2003;30:1508-1512
166. Ginzler EM, Aranow C. Mycophenolate mofetil in lupus nephritis. Lupus 2005;14:59-64
167. Husain S, Singh N. The impact of novel immunosuppressive agents on infections in organ transplant recipients and the interactions of these agents with antimicrobials. Clin Infect Dis 2002;35:53-61
168. Chan TM, Li FK, Tang CS, et al. Efficacy of mycophenolate mofetil in patients with diffuse proliferative lupus nephritis. Hong Kong-Guangzhou Nephrology Study Group. N Engl J Med 2000;343:1156-1162
169. Moore RA, Deny S. Systematic review and meta-analysis of randomised trials and cohort studies of mycophenolate mofetil in lupus nephritis. Arthritis Res Ther 2006; 8:R182
170. Joy MS, Hogan SL, Jennette JC, et al. A pilot study using mycophenolate mofetil in relapsing or resistant ANCA small vessel vasculitis. Nephrol Dial Transplant 2005;20: 2725-2732
171. Nowack R, Gobel U, Klooker P, et al. Mycophenolate mofetil for maintenance therapy of Wegener's granulomatosis and microscopic polyangiitis: a pilot study in 11 patients with renal involvement. J Am Soc Nephrol 1999;10: 1965-1971
172. Liossis SN, Bounas A, Andonopoulos AP. Mycophenolate mofetil as first-line treatment improves clinically evident early scleroderma lung disease. Rheumatology (Oxford) 2006;45:1005-1008
173. Kahan BD. Cyclosporine. N Engl J Med 1989;321:1725-1738
174. Miranda JM, Alvarez-Nemegyei J, Saavedra MA, et al. A randomized, double-blind, multicenter, controlled clinical trial of cyclosporine plus chloroquine vs. cyclosporine plus placebo in early-onset rheumatoid arthritis. Arch Med Res 2004;35:36-42
175. Kvien TK, Zeidler HK, Hannonen P, et al. Long term efficacy and safety of cyclosporin versus parenteral gold in early rheumatoid arthritis: a three year study of radiographic progression, renal function, and arterial hypertension. Ann Rheum Dis 2002;61:511-516
176. Schiff MH, Whelton A. Renal toxicity associated with disease-modifying antirheumatic drugs used for the treatment of rheumatoid arthritis. Semin Arthritis Rheum 2000;30:196-208
177. Proudman SM, Conaghan PG, Richardson C, et al. Treatment of poor-prognosis early rheumatoid arthritis: a randomized study of treatment with methotrexate, cyclosporin A, and intraarticular corticosteroids compared with sulfasalazine alone. Arthritis Rheum 2000;43:1809-1819
178. Yocum DE. The role of T-cells in rheumatoid arthritis and the use of immunomodulating drugs. Drugs Today (Barc) 1999;35:295-307
179. van den Borne BE, Landewé RB, Goei Thè HS, et al. Cyclosporin A therapy in rheumatoid arthritis: only strict application of the guidelines for safe use can prevent irreversible renal function loss. Rheumatology (Oxford) 1999;38:254-259
180. Wiederrecht G, Lam E, Hung S, et al. The mechanism of action of FK-506 and cyclosporin A. Ann N Y Acad Sci 1993;696:9-19
181. Schreiber SL, Crabtree GR. The mechanism of action of cyclosporin A and FK506. Immunol Today 1992;13:136-142
182. Wera S, Zheng L, Hooghe-Peters EL, et al. Cyclosporin A. rapamycin and FK506 decrease prolactin release from rat pituitary cells in primary culture. Endocr Res 1995;21:623-633
183. Timmerman LA, Clipstone NA, Ho SN, et al. Rapid shuttling of NF-AT in discrimination of Ca2+ signals and immunosuppression. Nature 1996;383:837-840
184. Kim WU, Cho ML, Kim SI, et al. Divergent effect of cyclosporine on Th1/Th2 type cytokines in patients with severe, refractory rheumatoid arthritis. J Rheumatol 2000; 27:324-331
185. Faulds D, Goa KL, Benfield P. Cyclosporin: a review of its pharmacodynamic and pharmacokinetic properties, and therapeutic use in immunoregulatory disorders. Drugs 1993;45:953-1040
186. Feutren G, Mihatsch MJ. Risk factors for cyclosporine-induced nephropathy in patients with autoimmune diseases. International Kidney Biopsy Registry of Cyclosporine in Autoimmune Diseases. N Engl J Med 1992;326:1654-1660
187. Palestine AG, Austin HA III, Balow JE, et al. Renal histopathologic alterations in patients treated with cyclosporine for uveitis. N Engl J Med 1986;314:1293-1298
188. Kopp JB, Klotman PE. Cellular and molecular mechanisms of cyclosporin nephrotoxicity. J Am Soc Nephrol 1990; 1:162-179
189. Keown P, Niese D. Cyclosporine microemulsion increases drug exposure and reduces acute rejection without incremental toxicity in de novo renal transplantation. International Sandimmun Neoral Study Group. Kidney Int 1998; 54:938-944
190. Miura K, Nakatani T, Asai T, et al. Role of hypomagnesemia in chronic cyclosporine nephropathy. Transplantation 2002;73:340-347
191. Foley RJ, Hamner RW, Weinman EJ. Serum potassium concentrations in cyclosporine- and azathioprine-treated renal transplant patients. Nephron 1985;40:280-285
192. Moyer TP, Post GR, Sterioff S, et al. Cyclosporine nephrotoxicity is minimized by adjusting dosage on the basis of drug concentration in blood. Mayo Clin Proc 1988; 63:241-247
193. Kahan BD, Welsh M, Urbauer DL, et al. Low intraindividual variability of cyclosporin A exposure reduces chronic rejection incidence and health care costs. J Am Soc Nephrol 2000;11:1122-1131
194. Dawidson I, Ar'Rajab A, Lu C, et al. Cyclosporine blood levels predict the likelihood of rejection and toxicity after simultaneous pancreas-kidney transplantation. Transplant Proc 1995;27:1324-1326
195. Burke JF Jr, Pirsch JD, Ramos EL, et al. Long-term efficacy and safety of cyclosporine in renal-transplant recipients. N Engl J Med 1994;331:358-363
196. Arellano F, Rrupp P. Malignancies in rheumatoid arthritis patients treated with cyclosporin A. Br J Rheumatol 1993; 32(Suppl 1):72-75
197. Feutren G. The optimal use of cyclosporin A in autoimmune diseases. J Autoimmun 1992;5(Suppl A):183-195
198. Kitridou RC. The mother in systemic lupus erythematosus. In: Wallace DJ, Hahn BH, Quasimorio FP Jr, et al., eds. Dubois' Lupus Erythematosus. Baltimore: Williams & Williams; 1997:967-1002
199. Sajjadi H, Soheilian M, Ahmadieh H, et al. Low dose cyclosporin-A therapy in Behçet's disease. J Ocul Pharmacol 1994;10:553-560
200. Lebwohl M, Ellis C, Gottlieb A, et al. Cyclosporine consensus conference: with emphasis on the treatment of psoriasis. J Am Acad Dermatol 1998;39:464-475
201. Wagner SA, Peter RU, Adam O, et al. Therapeutic efficacy of oral low-dose cyclosporin A in severe psoriatic arthritis. Dermatology 1993;186:62-67
202. Hallegua D, Wallace DJ, Metzger AL, et al. Cyclosporine for lupus membranous nephritis: experience with ten patients and review of the literature. Lupus 2000;9:241-251
203. Landewe RB, Goei The HS, van Rijthoven AW, et al. A randomized, double-blind, 24-week controlled study of low-dose cyclosporine versus chloroquine for early rheumatoid arthritis. Arthritis Rheum 1994;37:637-643
204. Mobini N, Padilla T Jr, Ahmed AR. Long-term remission in selected patients with Pemphigus vulgaris treated with cyclosporine. J Am Acad Dermatol 1997;36(2 Pt 1):264-266
205. Evans DJ, Cullinan P, Geddes DM. Cyclosporin as an oral corticosteroid sparing agent in stable asthma. Cochrane Database Syst Rev 2001;(2):CD002993