Low dose methotrexate in inflammatory bowel disease: Current status and future directions

American Journal of Gastroenterology

Volumn 98, Issue 3, 2003, Pages 530-537

  Schröder, Oliver ^a   Stein, Jürgen ^a,b  

^a GOETHE UNIVERSITY   (Germany)

^b Zentrum der Inneren Medizin   (Germany)

Author keywords

[No Author keywords available]

Indexed keywords

ACETYLSALICYLIC ACID; ANTIINFLAMMATORY AGENT; AZATHIOPRINE; COTRIMOXAZOLE; CYCLOSPORIN A; GLUCOCORTICOID; HYDROXYCHLOROQUINE; INFLIXIMAB; LEFLUNOMIDE; MERCAPTOPURINE; METHOTREXATE; NONSTEROID ANTIINFLAMMATORY AGENT; PREDNISONE; PROBENECID; SALAZOSULFAPYRIDINE; SULFAMETHOXAZOLE; TRIMETHOPRIM;

ABDOMINAL DISTENSION; ABDOMINAL PAIN; ALOPECIA; ANOREXIA; ANTIINFLAMMATORY ACTIVITY; ARTHRALGIA; BONE MARROW DEPRESSION; CHILL; COMMON COLD; CROHN DISEASE; CYTOPENIA; DIARRHEA; DRUG ABSORPTION; DRUG BIOAVAILABILITY; DRUG CONTRAINDICATION; DRUG DOSE REDUCTION; DRUG EFFICACY; DRUG EXCRETION; DRUG TOLERABILITY; DRUG TOLERANCE; DRUG TOXICITY; ENTERITIS; FATIGUE; FEVER; FLU LIKE SYNDROME; HEADACHE; HERPES ZOSTER; HUMAN; INFECTION; INSOMNIA; LEUKOPENIA; LIVER CIRRHOSIS; LIVER FIBROSIS; LONG TERM CARE; MAINTENANCE THERAPY; MYALGIA; NAUSEA; PAIN; PARESTHESIA; PATIENT SELECTION; PNEUMONIA; PRIORITY JOURNAL; PSORIASIS; RASH; RELAPSE; REMISSION; REVIEW; RHEUMATOID ARTHRITIS; SIDE EFFECT; STOMATITIS; THORAX PAIN; THROMBOCYTOPENIA; ULCERATIVE COLITIS; VOMITING;

EID: 0037345575     PISSN: 00029270     EISSN: None     Source Type: Journal    
DOI: 10.1111/j.1572-0241.2003.07305.x     Document Type: Review

References (60)

1. Schnabel A, Gross WL. Low dose methotrexate in rheumatic diseases - efficacy, side effects, and risk factors for side effects. Semin Arthritis Rheum 1994;23:310-27.
2. Schnabel A. Methotrexate: Mechanisms of action, pharmacology and toxicology. In: Fellermann K, Jewell DP, Sandborn WJ, et al., eds. Immunosuppresssion in inflammatory bowel diseases. Standards, new developments, future trends. Dordrecht: Kluwer Academic Publishers, 2001:113-8.
3. Kipen Y, Littlejohn GO, Morand EF. Methotrexate use in systemic lupus erythematosus. Lupus 1997;6:385-9.
4. Pachman LM, Hayford JR, Chung A, et al. Juvenile dermatomyositis at diagnosis: Clinical characteristics of 79 children. J Rheumatol 1998;25:1198-204.
5. de Groot K, Muhler M, Reinhold-Keller E, et al. Induction of remission in Wegener's granulomatosis with low dose methotrexate. J Rheumatol 1998;25:492-5.
6. Marin MG. Low dose methotrexate spares steroid usage in steroid-dependent asthmatic patients: A meta-analysis. Chest 1997;112:29-33.
7. 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: 60-6.
8. Chabner BA, Allegra CJ, Curt C, et al. Polyglutamation of methotrexate. Is methotrexate a prodrug? J Clin Invest 1985; 76:907-12.
9. Allegra CJ, Chabner BA, Drake JC, et al. Enhanced inhibition of thymidylate synthase by methotrexate polyglutamates. J Biol Chem 1985;260:9720-6.
10. Goldman ID, Matherly LH. The cellular pharmacology of methotrexate. Pharmacol Ther 1985;28:77-102.
11. Allegra CJ, Hoang K, Chao Yeh G, et al. Evidence of direct inhibition of de novo synthesis in human MCF-7 cells as a principle mode of metabolic inhibition by methotrexate. J Biol Chem 1987;262:13520-6.
12. Allegra CJ, Drake JC, Jolivet J, et al. Inhibition of phophoribosyl aminoimidazolecarboxamide transformylase by methotrexate and dihydrofolic acid polyglutamates. Proc Natl Acad Sci USA 1985;82:4881-5.
13. Bagott JE, Vaughan WH, Hudson BB. Inhibition of 5-amino-imidazole-4-carboxamide ribotide transformylase, adenosine deaminase and 5′adenylate deaminase by polyglutamates of methotrexate and oxidized folates and by 5-aminoimidazole- 4-carboxamide riboside and ribotide. Biochem J 1986;236: 193-200.
14. Ha T, Morgan SL, Vaughan WH, et al. Inhibition of adenosine deaminase and 5-adenosyl homocysteine hydrolase by 5-aminoimidazole-4-carboxamide riboside. FASEB J 1992;6: 1210-5.
15. Morabito L, Montesinos MC, Schreibman DM, et al. Methotrexate and sulfasalazine promote adenosine release by a mechanism that requires ecto-5′-nucleotidase-mediated conversion of adenine nucleotides. J Clin Invest 1998;101:295-300.
16. Cronstein BN, Naime D, Ostad E. The antiinflammatory mechanism of methotrexate: Increased adenosine release at inflamed sites diminishes leukocyte accumulation in an in vitro model of inflammation. J Clin Invest 1993;92:2675-82.
17. Cronstein BN, Kramer SB, Weismann G, et al. Adenosine: A physiological modulator of superoxide anion generation by human neutrophils. J Exp Med 1983;158:1160-77.
18. Cronstein BN, Rosenstein ED, Kramer SB, et al. Adenosine, a physiologic modulator of superoxide anion generation by human neutrophils. Adenosine acts via an A2 receptor on human neutrophils. J Immunol 1985;135:1366-71.
19. Cronstein BN, Levin RE, Philips MR, et al. Neutrophil adherence to endothelium is enhanced via adenosine A1 receptors and inhibited via adenosine A2 receptors. J Immunol 192;148: 2201-6.
20. Krump E, Lemay G, Borgeat D. Adenosine A2 receptor-induced inhibition of leukotriene B4 synthesis in whole blood ex vivo. Br J Pharmacol 1996;117:1639-44.
21. Thiel M, Chouker A. Acting via A2 receptors, adenosine inhibits production of tumor necrosis factor α of endotoxin- stimulated polymorphonuclear leukocytes. J Lab Clin Med 1995;126:275-82.
22. Saijadi FG, Takabayashi K, Foster AC, et al. Inhibition of TNFα expression by adenosine. Role of A3 adenosine receptors. J Immunol 1996;156:3435-42.
23. Bouma MG, Stad RK, van den Wildenberg FA, et al. Differential regulatory effects of adenosine on cytokine release by activated human monocates. J Immunol 1994;1:4159-68.
24. Le Moine O, Stordeur P, Schandene L, et al. Adenosine enhances IL-10 secretion by human monocytes. J Immunol 1996;156:4408-14.
25. Cronstein BN. The mechanism of action of methotrexate. Rheum Dis Clin North Am 1997;23:739-55.
26. Roenigk HH Jr, Auerbach R, Maibach H, et al. Methotrexate in psoriasis: Revised guidelines. J Am Acad Dermatol 1988; 19:145-56.
27. Kremer JM, Alarcon GS, Lightfood RW Jr, et al. Methotrexate for rheumatoid arthritis. Suggested guideline for monitoring liver toxicity. Arthritis Rheum 1994;37:316-28.
28. Kozarek RA, Bredfeldt JE, Rosoff JE. Does chronic methotrexate (MTX) cause liver toxicity when use for refractory inflammatory bowel disease (IBD)? Gastroenterology 1991; 100:A223.
29. Te HS, Schiano TD, Hanauer SB, et al. Hepatic effects of long-term methotrexate use in the treatment of inflammatory bowel disease. Am J Gastroenterol 2000;95:3150-6.
30. Van Ede AE, Laan RFJM, Blom HJ, et al. Methotrexate in rheumatoid arthritis: An update with focus on mechanisms involved in toxicity. Semin Arthritis Rheum 1998;27:277-92.
31. Grove ME, Hassell AB, Hsy EM, et al. Adverse reactions to disease-modifying anti-rheumatic drugs in clinical practice. Q J Med 2001;94:309-19.
32. Munkholm P, Langholz E, Davidsen M, et al. Frequency of glucocorticoid resistance and dependency in Crohn's disease. Gut 1994;35:360-2.
33. O'Donoghue DP, Dawson AM, Powell-Tuck J, et al. Double-blind withdrawal trial of azathioprine as maintenance treatment for Crohn's disease. Lancet 1978;2:955-7.
34. Candy S, Wright J, Gerber M, et al. A controlled double blind study of azathioprine in the management of Crohn's disease. Gut 1995;37:674-8.
35. Kozarek RA, Patterson DJ, Gelfand MD, et al. Methotrexate induces clinical and histologic remission in patients with refractory inflammatory disease. Ann Intern Med 1989;110: 353-6.
36. Feagan BG, Rochon J, Fedorak RN, et al. Methotrexate for the treatment of Crohn's disease. N Engl J Med 1995;332:292-7.
37. Oren R, Moshkowitz M, Odes S, et al. Methotrexate in chronic active Crohn's disease: A double-blind, randomized, Israeli multicenter trial. Am J Gastroenterol 1997;92:2203-9.
38. Arora S, Katkov W, Cooley J, et al. Methotrexate in Crohn's disease: Results of a randomized, double-blind, placebo-controlled trial. Hepatogastroenterology 1999;46:1724-9.
39. Vandeputte L, D'Haens G, Baert F, et al. Methotrexate in refractory Crohn's disease. Inflamm Bowel Dis 1999;5:11-5.
40. Lémann M, Zenjari T, Bouhnik T, et al. Methotrexate in Crohn's disease: Long-term efficacy and toxicity. Am J Gastroenterol 2000;95:1730-4.
41. Chong RY, Hanauer SB, Cohen RD. Efficacy of methotrexate in refractory Crohn's disease. Aliment Pharmacol Ther 2001; 15:35-44.
42. Fraser AG, Morton D, McGovern D, et al. The efficacy of methotrexate for maintaining remission in inflammatory bowel disease. Aliment Pharmacol Ther 2002;16:693-7.
43. Feagan BG, Fedorak RN, Irvine EJ, et al. A comparison of methotrexate with placebo for the maintenance of remission in Crohn's disease. N Engl J Med 2000;342:1627-32.
44. Mahadevan U, Marion JF, Present DH. The place for methotrexate in the treatment of refractory Crohn's disease. Gastroenterology 1997;112:A1031.
45. Baron TH, Truss CD, Elson CO. Low dose oral methotrexate in refractory inflammatory bowel disease. Dig Dis Sci 1993; 38:1851-6.
46. Egan LJ, Sandborn WJ, Tremaine WJ, et al. A randomized dose-response and pharmacokinetic study of methotrexate for refractory inflammatory Crohn's disease and ulcerative colitis. Aliment Pharmacol Ther 1999;13:1597-604.
47. Oren R, Arber N, Odes S, et al. Methotrexate in chronic active ulcerative colitis: A double blind, randomized, Israeli multicenter trial. Gastroenterology 1996;110:1416-21.
48. Haagsma CJ, van Riel PL, de Jong AJ, et al. Combination of sulphasalazine and methotrexate versus the single components in early rheumatoid arthritis: A randomized, controlled, double-blind, 52 week clinical trial. Br J Rheumatol 1997;36: 1082-8.
49. Ferraz MB, Pinheiro GR, Helfenstein M, et al. Combination therapy with methotrexate and chloroquine in rheumatoid arthritis. A multicenter randomized placebo-controlled trial. Scand J Rheumatol 1994;23:231-6.
50. Tugwell P, Pincus T, Yocum D, et al. Combination therapy with cyclosporine and methotrexate in severe rheumatoid arthritis. The methotrexate-cyclosporine combination study group. N Engl J Med 1995;333:137-41.
51. Stein CM, Pincus T, Yocum D, et al. Combination treatment of severe rheumatoid arthritis with cyclosporine and methotrexate for forty-eight weeks: An open-label extension study. The Methotrexate-Cyclosporine Combination Study Group. Arthritis Rheum 1997;40:1843-51.
52. O'Dell JR, Haire CE, Erikson N, et al. Treatment of rheumatoid arthritis with methotrexate alone, sulfasalazine and hydroxychloroquine, or a combination of all three medications. N Engl J Med 1996;334:1287-91.
53. Weinblatt ME, Kremer JM, Coblyn JS, et al. Pharmacokinetics, safety, and efficacy of combination treatment with methotrexate and leflunomide in patients with active rheumatoid arthritis. Arthritis Rheum 1999;42:1322-8.
54. Wilkens RF, Urowitz MB, Stablein DM, et al. Comparison of azathioprine, methotrexate, and the combination of both in the treatment of rheumatoid arthritis. A controlled clinical trial. Arthritis Rheum 1992;35:1799-806.
55. Maini RN, Breedveld FC, Kalden JR, et al. Therapeutic efficacy of multiple intravenous infusions of anti-tumor necrosis factor alpha monoclonal antibody combined with low dose weekly methotrexate in rheumatoid arthritis. Arthritis Rheum 1998;41:1552-63.
56. Bingham S, Emery P. Combination therapy in rheumatoid arthritis. Springer Semin Immunopathol 2001;23:165-83.
57. Ogilvie AL, Antoni C, Dechant C, et al. Treatment of psoriatic arthritis with antitumour necrosis factor-alpha antibody clears skin lesions of psoriasis resistant to treatment with methotrexate. Br J Dermatol 2001;144:587-9.
58. Lipsky PE, van der Heijde DM, St Clair EW, et al. Infliximab and methotrexate in the treatment of rheumatoid arthritis. Anti-Tumor Necrosis Factor Trial in Rheumatoid Arthritis with concomitant Therapy Study Group. N Engl J Med 2000; 343:1594-602.
59. Ochsenkühn T, Göke B, Sackmann M. Combining infliximab with 6-mercaptopurine/azathioprine for fistula therapy in Crohn's disease. Am J Gastroenterol 2002;97:2022-5.
60. Schröder O, Stein J. Methotrexat und Infliximab in der Therapie des mittel-bis schwergradigen therapierefraktären Morbus Crohn. Z Gastroenterol 2002;40:A705.