Incidence and prevention of bladder toxicity from cyclophosphamide in the treatment of rheumatic diseases: A data-driven review

Arthritis and Rheumatism

Volumn 62, Issue 1, 2010, Pages 9-21

  Monach, Paul A ^a   Arnold, Lindsay M ^a   Merkel, Peter A ^a  

^a BOSTON MEDICAL CENTER   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

CYCLOPHOSPHAMIDE; CYTOCHROME P450; DIMESNA; IFOSFAMIDE; INFUSION FLUID; MESNA;

AUTOIMMUNE DISEASE; BLADDER CANCER; CANCER RISK; CELL DEATH; CELL DIVISION; CLINICAL TRIAL; DNA CROSS LINKING; DRUG BINDING; DRUG BIOAVAILABILITY; DRUG CLEARANCE; DRUG DOSAGE FORM COMPARISON; DRUG EFFICACY; DRUG EXCRETION; DRUG HYPERSENSITIVITY; DRUG INTERMITTENT THERAPY; DRUG MEGADOSE; DRUG METABOLISM; GASTROINTESTINAL TOXICITY; HEMORRHAGIC CYSTITIS; HUMAN; HYDRATION; INCIDENCE; LUPUS ERYTHEMATOSUS NEPHRITIS; MICROSCOPIC POLYANGIITIS; MYOSITIS; NONHODGKIN LYMPHOMA; NONHUMAN; POLYARTERITIS NODOSA; PRIORITY JOURNAL; REVIEW; RHEUMATIC DISEASE; SARCOMA; SMOKING; SYSTEMIC LUPUS ERYTHEMATOSUS; SYSTEMIC SCLEROSIS; VASCULITIS; WEGENER GRANULOMATOSIS;

ANTIRHEUMATIC AGENTS; CYCLOPHOSPHAMIDE; CYSTITIS; DATABASES, BIBLIOGRAPHIC; HUMANS; INCIDENCE; MESNA; PROTECTIVE AGENTS; RHEUMATIC DISEASES; URINARY BLADDER NEOPLASMS;

EID: 74849100964     PISSN: 00043591     EISSN: 15290131     Source Type: Journal    
DOI: 10.1002/art.25061     Document Type: Review

References (96)

1. Austin HA III, Klippel JH, Balow JE, le Riche NG, Steinberg AD, Plotz PH, et al. Therapy of lupus nephritis: controlled trial of prednisone and cytotoxic drugs. N Engl J Med 1986;314:614-9.
2. Fauci AS, Katz P, Haynes BF, Wolff SM. Cyclophosphamide therapy of severe systemic necrotizing vasculitis. N Engl J Med 1979;301:235-8.
3. Gourley MF, Austin HA III, Scott D, Yarboro CH, Vaughan EM, Muir J, et al. Methylprednisolone and cyclophosphamide, alone or in combination, in patients with lupus nephritis: a randomized, controlled trial. Ann Intern Med 1996;125:549-57.
4. Tashkin DP, Elashoff R, Clements PJ, Goldin J, Roth MD, Furst DE, et al. Cyclophosphamide versus placebo in scleroderma lung disease. N Engl J Med 2006;354:2655-66.
5. Mukhtyar C, Guillevin L, Cid MC, Dasgupta B, de Groot K, Gross W, et al. EULAR recommendations for the management of primary small and medium vessel vasculitis. Ann Rheum Dis 2009;68:310-7.
6. Ginzler EM, Dooley MA, Aranow C, Kim MY, Buyon J, Merrill JT, et al. Mycophenolate mofetil or intravenous cyclophosphamide for lupus nephritis. N Engl J Med 2005;353:2219-28.
7. Wegener's Granulomatosis Etanercept Trial (WGET) Research Group. Etanercept plus standard therapy for Wegener's granulomatosis. N Engl J Med 2005;352:351-61.
8. Hoyles RK, Ellis RW, Wellsbury J, Lees B, Newlands P, Goh NS, 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;54:3962-70.
9. Jayne DR, Gaskin G, Rasmussen N, Abramowicz D, Ferrario F, Guillevin L, et al. Randomized trial of plasma exchange or high-dosage methylprednisolone as adjunctive therapy for severe renal vasculitis. J Am Soc Nephrol 2007;18:2180-8.
10. Pedersen-Bjergaard J, Ersboll J, Hansen VL, Sorensen BL, Christoffersen K, Hou-Jensen K, et al. Carcinoma of the urinary bladder after treatment with cyclophosphamide for non-Hodgkin's lymphoma. N Engl J Med 1988;318:1028-32.
11. Brade WP, Herdrich K, Varini M. Ifosfamide: pharmacology, safety and therapeutic potential. Cancer Treat Rev 1985;12:1-47.
12. Stone JH. General principles of the use of cyclophosphamide in rheumatic and renal diseases. UpToDate online 2008; version 16.3. Online at http://uptodateonline.com.
13. Boumpas DT, Illei GG, Balow JE. Treatment: renal involvement. In: Hochberg MC, Silman AJ, Smolen JS, Weinblatt ME, Weisman MH, editors. Rheumatology. 3rd ed. Edinburgh: Mosby; 2003. p. 1405-17.
14. Wofsy D. Therapy of systemic lupus erythematosus. In: Koopman WJ, Moreland LW, editors. Arthritis and allied conditions: a textbook of rheumatology. 15th ed. Philadelphia: Lippincott Williams & Wilkins; 2005. p. 1561-74.
15. Cohen MH, Dagher R, Griebel DJ, Ibrahim A, Martin A, Scher NS, et al. U.S. Food and Drug Administration drug approval summaries: imatinib mesylate, mesna tablets, and zoledronic acid. Oncologist 2002;7:393-400.
16. Hensley ML, Schuchter LM, Lindley C, Meropol NJ, Cohen GI, Broder G, et al. American Society of Clinical Oncology clinical practice guidelines for the use of chemotherapy and radiotherapy protectants. J Clin Oncol 1999;17:3333-55.
17. Richmond R, McMillan TW, Luqmani RA. Optimisation of cyclophosphamide therapy in systemic vasculitis. Clin Pharmacokinet 1998;34:79-90.
18. Cyclophosphamide. In: Dorr RT, Von Hoff DD, editors. Cancer chemotherapy handbook. 2nd ed. Norwalk, Connecticut: Appleton & Lange; 1994. p. 319-32.
19. Brock N. Comparative pharmacologic study in vitro and in vivo with cyclophosphamide (NSC-26271), cyclophosphamide metabolites, and plain nitrogen mustard compounds. Cancer Treat Rep 1976;60:301-8.
20. Brock N, Stekar J, Pohl J, Niemeyer U, Scheffler G. Acrolein, the causative factor of urotoxic side-effects of cyclophosphamide, ifosfamide, trofosfamide and sufosfamide. Arzneimittelforschung 1979;29:659-61.
21. Batista CK, Brito GA, Souza ML, Leitao BT, Cunha FQ, Ribeiro RA. A model of hemorrhagic cystitis induced with acrolein in mice. Braz J Med Biol Res 2006;39:1475-81.
22. Sigal SH, Tomaszewski JE, Brooks JJ, Wein A, LiVolsi VA. Carcinosarcoma of bladder following long-term cyclophosphamide therapy. Arch Pathol Lab Med 1991;115:1049-51.
23. Stein JP, Skinner EC, Boyd SD, Skinner DG. Squamous cell carcinoma of the bladder associated with cyclophosphamide therapy for Wegener's granulomatosis: a report of 2 cases. J Urol 1993;149:588-9.
24. Chasko SB, Keuhnelian JG, Gutowski WT III, Gray GF. Spindle cell cancer of bladder during cyclophosphamide therapy for Wegener's granulomatosis. Am J Surg Pathol 1980;4:191-6.
25. Struck RF, Alberts DS, Horne K, Phillips JG, Peng YM, Roe DJ. Plasma pharmacokinetics of cyclophosphamide and its cytotoxic metabolites after intravenous versus oral administration in a randomized, crossover trial. Cancer Res 1987;47:2723-6.
26. Cytoxan prescribing information. Princeton (NJ): Bristol-Myers Squibb; 2005.
27. Jayne D, Rasmussen N, Andrassy K, Bacon P, Tervaert JW, Dadoniene J, et al. A randomized trial of maintenance therapy for vasculitis associated with antineutrophil cytoplasmic autoantibodies. N Engl J Med 2003;349:36-44.
28. De Groot K, Jayne D, Tesar V, Savage C. Randomised controlled trial of daily oral versus pulse cyclophosphamide for induction of remission in ANCA-associated systemic vasculitis. Kidney Blood Press Res 2005;28:195.
29. Illei GG, Austin HA, Crane M, Collins L, Gourley MF, Yarboro CH, et al. Combination therapy with pulse cyclophosphamide plus pulse methylprednisolone improves long-term renal outcome without adding toxicity in patients with lupus nephritis. Ann Intern Med 2001;135:248-57.
30. Bertsias G, Ioannidis JP, Boletis J, Bombardieri S, Cervera R, Dostal C, et al. EULAR recommendations for the management of systemic lupus erythematosus. Report of a Task Force of the EULAR Standing Committee for International Clinical Studies Including Therapeutics. Ann Rheum Dis 2008;67:195-205.
31. Silver RM, Warrick JH, Kinsella MB, Staudt LS, Baumann MH, Strange C. Cyclophosphamide and low-dose prednisone therapy in patients with systemic sclerosis (scleroderma) with interstitial lung disease. J Rheumatol 1993;20:838-44.
32. Stillwell TJ, Benson RC Jr, DeRemee RA, McDonald TJ, Weiland LH. Cyclophosphamide-induced bladder toxicity in Wegener's granulomatosis. Arthritis Rheum 1988;31:465-70.
33. Talar-Williams C, Hijazi YM, Walther MM, Linehan WM, Hallahan CW, Lubensky I, et al. Cyclophosphamide-induced cystitis and bladder cancer in patients with Wegener granulomatosis. Ann Intern Med 1996;124:477-84.
34. Reinhold-Keller E, Beuge N, Latza U, de Groot K, Rudert H, Nolle B, et al. An interdisciplinary approach to the care of patients with Wegener's granulomatosis: long-term outcome in 155 patients. Arthritis Rheum 2000;43:1021-32.
35. Plotz PH, Klippel JH, Decker JL, Grauman D, Wolff B, Brown BC, et al. Bladder complications in patients receiving cyclophosphamide for systemic lupus erythematosus or rheumatoid arthritis. Ann Intern Med 1979;91:221-3.
36. Carette S, Klippel JH, Decker JL, Austin HA, Plotz PH, Steinberg AD, et al. Controlled studies of oral immunosuppressive drugs in lupus nephritis: a long-term follow-up. Ann Intern Med 1983;99:1-8.
37. Aptekar RG, Atkinson JP, Decker JL, Wolff SM, Chu EW. Bladder toxicity with chronic oral cyclophosphamide therapy in nonmalignant disease. Arthritis Rheum 1973;16:461-7.
38. Radis CD, Kahl LE, Baker GL, Wasko MC, Cash JM, Gallatin A, et al. Effects of cyclophosphamide on the development of malignancy and on long-term survival of patients with rheumatoid arthritis: a 20-year followup study. Arthritis Rheum 1995;38:1120-7.
39. Townes AS, Sowa JM, Shulman LE. Controlled trial of cyclophosphamide in rheumatoid arthritis. Arthritis Rheum 1976;19:563-73.
40. Westman KW, Bygren PG, Olsson H, Ranstam J, Wieslander J. Relapse rate, renal survival, and cancer morbidity in patients with Wegener's granulomatosis or microscopic polyangiitis with renal involvement. J Am Soc Nephrol 1998;9:842-52.
41. Faurschou M, Sorensen IJ, Mellemkjaer L, Loft AG, Thomsen BS, Tvede N, et al. Malignancies in Wegener's granulomatosis: incidence and relation to cyclophosphamide therapy in a cohort of 293 patients. J Rheumatol 2008;35:100-5.
42. Knight A, Askling J, Granath F, Sparen P, Ekbom A. Urinary bladder cancer in Wegener's granulomatosis: risks and relation to cyclophosphamide. Ann Rheum Dis 2004;63:1307-11.
43. Knight A, Askling J, Ekbom A. Cancer incidence in a population-based cohort of patients with Wegener's granulomatosis. Int J Cancer 2002;100:82-5.
44. Travis LB, Curtis RE, Glimelius B, Holowaty EJ, Van Leeuwen FE, Lynch CF, et al. Bladder and kidney cancer following cyclo phosphamide therapy for non-Hodgkin's lymphoma. J Natl Cancer Inst 1995;87:524-30.
45. Cancer statistics, cancer fact sheets, urinary bladder. Surveillance, Epidemiology and End Results (SEER) online 2008. http://seer. cancer.gov/statfacts/html/urinb.
46. Zeegers MP, Kellen E, Buntinx F, van den Brandt PA. The association between smoking, beverage consumption, diet and bladder cancer: a systematic literature review. World J Urol 2004;21:392-401.
47. De Groot K, Adu D, Savage CO. The value of pulse cyclop-hosphamide in ANCA-associated vasculitis: meta-analysis and critical review. Nephrol Dial Transplant 2001;16:2018-27.
48. Hoffman GS, Leavitt RY, Fleisher TA, Minor JR, Fauci AS. Treatment of Wegener's granulomatosis with intermittent highdose intravenous cyclophosphamide. Am J Med 1990;89:403-10.
49. Goransson LG, Brodin C, Ogreid P, Janssen EA, Romundstad PR, Vatten L, et al. Intravenous cyclophosphamide in patients with chronic systemic inflammatory diseases: morbidity and mortality. Scand J Rheumatol 2008;37:130-4.
50. Martin F, Lauwerys B, Lefebvre C, Devogelaer JP, Houssiau FA. Side-effects of intravenous cyclophosphamide pulse therapy. Lupus 1997;6:254-7.
51. Koldingsnes W, Gran JT, Omdal R, Husby G. Wegener's granulomatosis: long-term follow-up of patients treated with pulse cyclophosphamide. Br J Rheumatol 1998;37:659-64.
52. Haubitz M, Schellong S, Gobel U, Schurek HJ, Schaumann D, Koch KM, et al. Intravenous pulse administration of cyclophosphamide versus daily oral treatment in patients with antineutrophil cytoplasmic antibody-associated vasculitis and renal involvement: a prospective, randomized study. Arthritis Rheum 1998;41:1835-44.
53. Guillevin L, Cordier JF, Lhote F, Cohen P, Jarrousse B, Royer I, et al. A prospective, multicenter, randomized trial comparing steroids and pulse cyclophosphamide versus steroids and oral cyclophosphamide in the treatment of generalized Wegener's granulomatosis. Arthritis Rheum 1997;40:2187-98.
54. Adu D, Pall A, Luqmani RA, Richards NT, Howie AJ, Emery P, et al. Controlled trial of pulse versus continuous prednisolone and cyclophosphamide in the treatment of systemic vasculitis. QJM 1997;90:401-9.
55. Martin-Suarez I, D'Cruz D, Mansoor M, Fernandes AP, Khamashta MA, Hughes GR. Immunosuppressive treatment in severe connective tissue diseases: effects of low dose intravenous cyclophosphamide. Ann Rheum Dis 1997;56:481-7.
56. Ortiz A, Gonzalez-Parra E, Alvarez-Costa G, Egido J. Bladder cancer after cyclophosphamide therapy for lupus nephritis. Nephron 1992;60:378-9.
57. Chow SK, Looi LM, Loh CS, Yeap SS. Cyclophosphamide-induced transitional cell carcinoma of bladder in lupus nephritis. Intern Med J 2002;32:114-6.
58. Alivizatos G, Dimopoulou I, Mitropoulos D, Dimopoulos AM, Koufakis I, Lykourinas M. Bladder cancer in a young girl with systemic lupus erythematosus treated with cyclophosphamide. Acta Urol Belg 1991;59:133-7.
59. Bernatsky S, Boivin JF, Joseph L, Rajan R, Zoma A, Manzi S, et al. An international cohort study of cancer in systemic lupus erythematosus. Arthritis Rheum 2005;52:1481-90.
60. Tarr T, Gyorfy B, Szekanecz E, Bhattoa HP, Zeher M, Szegedi G, et al. Occurrence of malignancies in Hungarian patients with systemic lupus erythematosus: results from a single center. Ann N Y Acad Sci 2007;1108:76-82.
61. Ragnarsson O, Grondal G, Steinsson K. Risk of malignancy in an unselected cohort of Icelandic patients with systemic lupus erythematosus. Lupus 2003;12:687-91.
62. Sultan SM, Ioannou Y, Isenberg DA. Is there an association of malignancy with systemic lupus erythematosus? An analysis of 276 patients under long-term review. Rheumatology (Oxford) 2000;39:1147-52.
63. Abu-Shakra M, Gladman DD, Urowitz MB. Malignancy in systemic lupus erythematosus. Arthritis Rheum 1996;39:1050-4.
64. Sweeney DM, Manzi S, Janosky J, Selvaggi KJ, Ferri W, Medsger TA Jr, et al. Risk of malignancy in women with systemic lupus erythematosus. J Rheumatol 1995;22:1478-82.
65. Nived O, Bengtsson A, Jonsen A, Sturfelt G, Olsson H. Malignancies during follow-up in an epidemiologically defined systemic lupus erythematosus inception cohort in southern Sweden. Lupus 2001;10:500-4.
66. Dechant KL, Brogden RN, Pilkington T, Faulds D. Ifosfamide/ mesna: a review of its antineoplastic activity, pharmacokinetic properties and therapeutic efficacy in cancer. Drugs 1991;42:428-67.
67. Mesna. In: Dorr RT, Von Hoff DD, editors. Cancer chemotherapy handbook. 2nd ed. Norwalk (CT): Appleton & Lange; 1994. p. 685-91.
68. Dorr RT. Chemoprotectants for cancer chemotherapy. Semin Oncol 1991;18(1 Suppl 2):48-58.
69. Reinhold-Keller E, Mohr J, Christophers E, Nordmann K, Gross WL. Mesna side effects which imitate vasculitis. Clin Investig 1992;70:698-704.
70. Freedman A, Ehrlich RM, Ljung BM. Prevention of cyclophosphamide cystitis with 2-mercaptoethane sodium sulfonate: a histologic study. J Urol 1984;132:580-2.
71. Themann H, Oberdorf E, Brock N, Pohl J. Electron microscopic investigations of the cyclophosphamide-induced lesions of the urinary bladder of the rat and their prevention by mesna. Urol Int 1987;42:37-43.
72. Habs M, Hebebrand J, Schmahl D. Influence of sulfur-containing compounds on the acute toxicity of cyclophosphamide in male Sprague-Dawley rats. Arzneimittelforschung 1984;34:792-3.
73. Kedar A, Simpson CL, Williams P, Moore R, Tritsch G, Murphy GP. The prevention of cyclophosphamide-induced bladder swelling in the rat by I.V. administration of sodium-2-mercaptoethane sulfonate. Res Commun Chem Pathol Pharmacol 1980;29:339-48.
74. Cavalletti E, Tofanetti O, Zunino F. Comparison of reduced glutathione with 2-mercaptoethane sulfonate to prevent cyclophosphamide-induced urotoxicity. Cancer Lett 1986;32:1-6.
75. Sneller MC. Cystitis, bladder cancer, and myelodysplasia in patients with Wegener's granulomatosis: comment on the article by Reinhold-Keller et al [letter]. Arthritis Rheum 2000;43:2853-5.
76. Hows JM, Mehta A, Ward L, Woods K, Perez R, Gordon MY, et al. Comparison of mesna with forced diuresis to prevent cyclophosphamide induced haemorrhagic cystitis in marrow transplantation: a prospective randomised study. Br J Cancer 1984;50:753-6.
77. Shepherd JD, Pringle LE, Barnett MJ, Klingemann HG, Reece DE, Phillips GL. Mesna versus hyperhydration for the prevention of cyclophosphamide-induced hemorrhagic cystitis in bone marrow transplantation. J Clin Oncol 1991;9:2016-20.
78. Vose JM, Reed EC, Pippert GC, Anderson JR, Bierman PJ, Kessinger A, et al. Mesna compared with continuous bladder irrigation as uroprotection during high-dose chemotherapy and transplantation: a randomized trial. J Clin Oncol 1993;11:1306-10.
79. Sakurai M, Saijo N, Shinkai T, Eguchi K, Sasaki Y, Tamura T, et al. The protective effect of 2-mercapto-ethane sulfonate (MESNA) on hemorrhagic cystitis induced by high-dose ifosfamide treatment tested by a randomized crossover trial. Jpn J Clin Oncol 1986;16:153-6.
80. Fukuoka M, Negoro S, Masuda N, Furuse K, Kawahara M, Kodama N, et al. Placebo-controlled double-blind comparative study on the preventive efficacy of mesna against ifosfamideinduced urinary disorders. J Cancer Res Clin Oncol 1991;117:473-8.
81. Bryant BM, Jarman M, Ford HT, Smith IE. Prevention of isophosphamide-induced urothelial toxicity with 2-mercaptoethane sulphonate sodium (mesnum) in patients with advanced carcinoma. Lancet 1980;2:657-9.
82. Scheef W, Klein HO, Brock N, Burkert H, Gunther U, Hoefer-Janker H, et al. Controlled clinical studies with an antidote against the urotoxicity of oxazaphosphorines: preliminary results. Cancer Treat Rep 1979;63:501-5.
83. Mace JR, Keohan ML, Bernardy H, Junge K, Niebch G, Romeis P, et al. Crossover randomized comparison of intravenous versus intravenous/oral mesna in soft tissue sarcoma treated with highdose ifosfamide. Clin Cancer Res 2003;9(16 Pt 1):5829-34.
84. Scheulen ME, Niederle N, Bremer K, Schutte J, Seeber S. Efficacy of ifosfamide in refractory malignant diseases and uroprotection by mesna: results of a clinical phase II-study with 151 patients. Cancer Treat Rev 1983;10 Suppl A:93-101.
85. Pratt CB, Goren MP. Ifosfamide/mesna and hematuria. Cancer Treat Rep 1987;71:1124-5.
86. Antman KH, Montella D, Rosenbaum C, Schwen M. Phase II trial of ifosfamide with mesna in previously treated metastatic sarcoma. Cancer Treat Rep 1985;69:499-504.
87. Niederle N, Scheulen ME, Cremer M, Schutte J, Schmidt CG, Seeber S. Ifosfamide in combination chemotherapy for sarcomas and testicular carcinomas. Cancer Treat Rev 1983;10 Suppl A:129-35.
88. Stuart-Harris RC, Harper PG, Parsons CA, Kaye SB, Mooney CA, Gowing NF, et al. High-dose alkylation therapy using ifosfamide infusion with mesna in the treatment of adult advanced soft-tissue sarcoma. Cancer Chemother Pharmacol 1983;11:69-72.
89. Kemeny N, Reichman B, Dougherty J, Lipperman R, Cheng E. Phase II trial of ifosfamide and mesna in advanced colorectal cancer. Cancer Treat Rep 1987;71:663-4.
90. Scheef W, Soemer G. The treatment of solid malignant tumours with holoxan and uromitexan. In: Burkert N, Nagel GA, editors. Contributions to oncology. Basel (Switzerland): Karger; 1980. p. 21-4.
91. Lima MV, Ferreira FV, Macedo FY, de Castro Brito GA, Ribeiro RA. Histological changes in bladders of patients submitted to ifosfamide chemotherapy even with mesna prophylaxis. Cancer Chemother Pharmacol 2007;59:643-50.
92. Pratt CB. Current studies of ifosfamide for pediatric solid tumors and leukemia in the United States. Semin Oncol 1992;19(6 Suppl 12):43-9.
93. Habs MR, Schmahl D. Prevention of urinary bladder tumors in cyclophosphamide-treated rats by additional medication with the uroprotectors sodium 2-mercaptoethane sulfonate (mesna) and disodium 2,2'-dithio-bis-ethane sulfonate (dimesna). Cancer 1983;51:606-9.
94. Schuchter LM, Hensley ML, Meropol NJ, Winer EP. 2002 update of recommendations for the use of chemotherapy and radiotherapy protectants: clinical practice guidelines of the American Society of Clinical Oncology. J Clin Oncol 2002;20:2895-903.
95. Lapraik C, Watts R, Bacon P, Carruthers D, Chakravarty K, D'Cruz D, et al. BSR and BHPR guidelines for the management of adults with ANCA associated vasculitis. Rheumatology (Oxford) 2007;46:1615-6.
96. American College of Rheumatology Ad Hoc Committee on Systemic Lupus Erythematosus Guidelines. Guidelines for referral and management of systemic lupus erythematosus in adults. Arthritis Rheum 1999;42:1785-96.