Methotrexate: An old new drug in autoimmune disease

Expert Review of Clinical Immunology

Volumn 10, Issue 11, 2014, Pages 1519-1530

  Cipriani, Paola ^a   Ruscitti, Piero ^a   Carubbi, Francesco ^a   Liakouli, Vasiliki ^a   Giacomelli, Roberto ^a  

^a UNIVERSITY OF L'AQUILA   (Italy)

Author keywords

ankylosing spondylitis; granulomatosis with polyangiitis (Wegener's); inflammatory bowel diseases; mechanism of action; methotrexate; psoriasis; rheumatoid arthritis; side effects; systemic lupus erythematosus; systemic sclerosis

Indexed keywords

BIOLOGICAL PRODUCT; DISEASE MODIFYING ANTIRHEUMATIC DRUG; METHOTREXATE; STEROID; IMMUNOSUPPRESSIVE AGENT;

ADULT ONSET STILL DISEASE; ANKYLOSING SPONDYLITIS; ASCITES; AUTOIMMUNE DISEASE; BIOLOGICAL THERAPY; CELL DIVISION; CELL PROLIFERATION; COST BENEFIT ANALYSIS; DISEASE CONTROL; DRUG BLOOD LEVEL; DRUG COST; DRUG EFFICACY; DRUG ELIMINATION; DRUG INDUCED DISEASE; DRUG RETENTION; DRUG SAFETY; GIANT CELL ARTERITIS; IMMUNE SYSTEM; IMMUNOMODULATION; INFLAMMATORY BOWEL DISEASE; INFLAMMATORY DISEASE; LONG TERM CARE; LUNG FIBROSIS; LUNG LAVAGE; LUNG TOXICITY; LYMPHOCYTE COUNT; MORTALITY; MYOSITIS; OSTEOCLASTOGENESIS; PLEURA EFFUSION; PNEUMONIA; PSORIASIS; PSORIATIC ARTHRITIS; RANDOMIZED CONTROLLED TRIAL (TOPIC); REMISSION; REVIEW; RHEUMATIC POLYMYALGIA; RHEUMATOID ARTHRITIS; SYSTEMIC LUPUS ERYTHEMATOSUS; SYSTEMIC SCLEROSIS; TREATMENT RESPONSE; URINARY EXCRETION; WEGENER GRANULOMATOSIS; AUTOIMMUNE DISEASES; HUMAN; IMMUNOLOGY;

AUTOIMMUNE DISEASES; HUMANS; IMMUNOSUPPRESSIVE AGENTS; METHOTREXATE;

EID: 84911477709     PISSN: 1744666X     EISSN: 17448409     Source Type: Journal    
DOI: 10.1586/1744666X.2014.962996     Document Type: Review

References (81)

1. Pincus T, Yazici Y, Sokka T, et al. Methotrexate as the anchor drug for the treatment of early rheumatoid arthritis. Clin Exp Rheumatol 2003;21(5 Suppl 31): S179-85
2. Tian H, Cronstein BN. Understanding the mechanisms of action of methotrexate: implications for the treatment of rheumatoid arthritis. Bull NYU Hosp Jt Dis 2007;65:168-73
3. Borcher S. The Use of Methotrexate in Rheumatoid Arthritis Semin Arthritis Rheum. 2004;34:465-83
4. Genestier L, Paillot R, Quemeneur L, et al. Mechanisms of action of methotrexate. Immunopharmacology 2000;47:247-57
5. Grim J, Chládek J, Martnková J. Pharmacokinetics and pharmacodynamics of methotrexate in non-neoplastic diseases. Clin Pharmacokinet 2003;42:139-51
6. The effect of age and renal function on the efficacy and toxicity of methotrexate in rheumatoid arthritis. Rheumatoid Arthritis Clinical Trial Archive Group. J Rheumatol 1995;22:218-23
7. Nesher G, Moore TL. The in vitro effects of methotrexate on peripheral blood mononuclear cells. Modulation by methyl donors and spermidine. Arthritis Rheum 1990;33:954-9
8. Gerards AH, de Lathouder S, de Groot ER, et al. Inhibition of cytokine production by methotrexate. Studies in healthy volunteers and patients with rheumatoid arthritis. Rheumatology 2003;42:1189-96
9. Dolhain RJ, Tak PP, Dijkmans BA, et al. Methotrexate reduces inflammatory cell numbers, expression of monokines and of adhesion molecules in synovial tissue of patients with rheumatoid arthritis. Br J Rheumatol 1998;37:502-8
10. Rudwaleit M, Yin Z, Siegert S, et al. Response to methotrexate in early rheumatoid arthritis is associated with a decrease of T cell derived tumour necrosis factor alpha, increase of interleukin 10, and predicted by the initial concentration of interleukin 4. Ann Rheum Dis 2000;59: 311-14
11. Revu S, Nerega°rd P, af Klint E, et al. Synovial membrane immunohistology in early-untreated rheumatoid arthritis reveals high expression of catabolic bone markers that is modulated by methotrexate. Arthritis Res Ther 2013;15:R205
12. Pavy S, Constantin A, Thao P, et al. Methotrexate therapy for rheumatoid arthritis: clinical practice guidelines based on published evidence and expert opinion. Joint Bone Spine 2006;73:388-95
13. Visser K, Katchamart W, Loza E, et al. Multinational evidence-based recommendations for the use of methotrexate in rheumatic disorders with a focus on rheumatoid arthritis: integrating systematic literature research and expert opinion of a broad international panel of rheumatologists in the 3E Initiative. Ann Rheum Dis 2009;68:1086-93
14. Patanè M, Ciriaco M, Chimirri S, et al. Interactions among Low Dose of Methotrexate and Drugs Used in the Treatment of Rheumatoid Arthritis. Adv Pharmacol Sci 2013;2013:313858
15. Colebatch AN, Marks JL, van der Heijde DM, Edwards JC. Safety of nonsteroidal antiinflammatory drugs and/or paracetamol in people receiving methotrexate for inflammatory arthritis: a Cochrane systematic review. J Rheumatol 2012;90:62-73
16. Salliot C, van der Heijde D. Long-term safety of methotrexate monotherapy in patients with rheumatoid arthritis: a systematic literature research. Ann Rheum Dis 2009;68:1100-4
17. Visser K, van der Heijde D. Optimal dosage and route of administration of methotrexate in rheumatoid arthritis: a systematic review of the literature. Ann Rheum Dis 2009;68:1094-9
18. Rondon F1, Mendez O, Spinel N, et al. Methotrexate-induced pulmonary toxicity in psoriatic arthritis (PsA): case presentation and literature review. Clin Rheumatol 2011; 30(10):1379-84
19. Chikura B, Sathi N, Lane S, Dawson JK. Variation in immunological response in methotrexate-induced pneumonitis. Rheumatology 2008;47:1647-50
20. Kim YJ, Song M, Ryu JC. Inflammation in methotrexate induced pulmonary toxicity occurs via the p38 MAPK pathway. Toxicology 2009;27:183-90
21. Shidara K, Hoshi D, Inoue E, et al. Incidence of and risk factors for interstitial pneumonia in patients with rheumatoid arthritis in a large Japanese observational cohort, IORRA. Mod Rheumatol 2010;20: 280-6
22. Carson CW, Cannon GW, Egger MJ, et al. Pulmonary disease during the treatment of rheumatoid arthritis with low dose pulse methotrexate. Semin Arthritis Rheum 1987;16:186-95
23. Williams HJ, Willkens RF, Samuelson CO Jr, et al. Comparison of low-dose oral pulse methotrexate and placebo in the treatment of rheumatoid arthritis. A controlled clinical trial. Arthritis Rheum 1985;28:721-30
24. Weinblatt ME, Coblyn JS, Fox DA, et al. Efficacy of low-dose methotrexate in rheumatoid arthritis. N Engl J Med 1985;312:818-22
25. Weinblatt ME, Polisson R, Blotner SD. The effects of drug therapy on radiographic progression of rheumatoid arthritis. Results of a 36-week randomized trial comparing methotrexate and auranofin. Arthritis Rheum 1993;36:613-19
26. Kremer JM, Phelps CT. Long-term prospective study of the use of methotrexate in the treatment of rheumatoid arthritis. Update after a mean of 90 months. Arthritis Rheum 1992;35:138-45
27. Giacomelli R, Cipriani P, Matucci Cerinic M, et al. Combination therapy with cyclosporine and methotrexate in patients with early rheumatoid arthritis soon inhibits TNFalpha production without decreasing TNFalpha mRNA levels. An in vivo and in vitro study. Clin Exp Rheumatol 2002;20:365-72
28. Patel AM, Moreland LW. Certolizumab pegol: a new biologic targeting rheumatoid arthritis. Expert Rev Clin Immunol 2010; 6(6):855-66
29. Tanaka T, Ogata A, Narazaki M. Tocilizumab for the treatment of rheumatoid arthritis. Expert Rev Clin Immunol 2010;6(6):843-54
30. Singh JA, Furst DE, Bharat A, et al. 2012 update of the 2008 American College of Rheumatology recommendations for the use of disease-modifying antirheumatic drugs and biologic agents in the treatment of rheumatoid arthritis. Arthritis Care Res (Hoboken) 2012;64(5):625-39
31. Krieckaert CL, Bartelds GM, Lems WF, et al. The effect of immunomodulators on the immunogenicity of TNF-blocking therapeutic monoclonal antibodies: a review. Arthritis Res Ther 2010;12:217
32. van den Broek M, Lems WF, Allaart CF. BeSt practice: the success of early-targeted treatment in rheumatoid arthritis. Clin Exp Rheumatol 2012;30(4 Suppl 73):S35-8
33. Mouterde G, Baillet A, Gaujoux-Viala C, et al. Optimizing methotrexate therapy in rheumatoid arthritis: a systematic literature review. Joint Bone Spine 2011;78:587-92.
34. Hoekstra M, Haagsma C, Neef C, et al. Bioavailability of higher dose methotrexate comparing oral and subcutaneous administration in patients with rheumatoid arthritis. J Rheumatol 2004;31:645-8
35. Cipriani P, Ruscitti P, Carubbi F, et al. Methotrexate in rheumatoid arthritis: optimizing therapy among different formulations. Current and emerging paradigms. Clin Ther 2014;36(3):427-35
36. Pathirana D, Ormerod AD, Saiag P, et al. European S3: guidelines on the systemic treatment of psoriasis vulgaris. J Eur Acad Dermatol Venereol 2009;23:S1-70
37. Weinstein GD, Frost P. Methotrexate for psoriasis. A new therapeutic schedule. Arch Dermatol 1971;103:33-8
38. Kalb RE, Strober B, Weinstein G, Lebwohl M. Methotrexate and psoriasis: 2009 National Psoriasis Foundation Consensus Conference. J Am Acad Dermatol 2009;60:824-37
39. Montaudie H, Sbidian E, Paul C, et al. Methotrexate in psoriasis: a systematic review of treatment modalities, incidence, risk factors and monitoring of liver toxicity. J Eur Acad Dermatol Venereol 2011;25: S12-18
40. Haustein UF, Rytter M. Methotrexate in psoriasis: 26 years' experience with low-dose long-term treatment. J Euro Acad Dermatol Venereol 2000;14:382-8
41. Schmitt J, Rosumeck S, Thomaschewski G, et al. Efficacy and safety of systemic treatments for moderate-to-severe psoriasis: meta-analysis of randomized controlled trials. Br J Dermatol 2014;170(2):274-303
42. Black RL, O'Brien WM, Vanscott EJ, et al. Methotrexate therapy in psoriatic arthritis; double-blind study on 21 patients. JAMA 1964;189:743-7
43. Kingsley GH, Kowalczyk A, Taylor H, et al. A randomized placebo-controlled trial of methotrexate in psoriatic arthritis. Rheumatology (Oxford) 2012;51(8): 1368-77
44. Mease P. Methotrexate in psoriatic arthritis. Bull Hosp Jt Dis 2013;71(Suppl 1):S41-5.
45. Altan L, Bingol U, Karakoc Y, et al. Clinical investigation of methotrexate in the treatment of ankylosing spondylitis. Scand J Rheumatol 2001;30(5):255-9
46. Gonzalez-Lopez L, Garcia-Gonzalez A, Vazquez-Del-Mercado M, et al. Efficacy of methotrexate in ankylosing spondylitis: a randomized, double blind, placebo controlled trial. J Rheumatol 2004;31(8): 1568-74
47. Chen J, Veras MM, Liu C, Lin J. Methotrexate for ankylosing spondylitis. Cochrane Database Syst Rev 2013;2: CD004524
48. Haibel H, Brandt HC, Song IH, et al. No efficacy of subcutaneous methotrexate in active ankylosing spondylitis: a 16-week open-label trial. Ann Rheum Dis 2007; 66(3):419-21
49. Cappelli S, Bellando-Randone S, Guiducci S, Matucci-Cerinic M. Is immunosuppressive therapy the anchor treatment to achieve remission in systemic sclerosis Rheumatology (Oxford) 2013. [Epub ahead of print]
50. van den Hoogen FH, Boerbooms AM, Swaak AJ, et al. Comparison of methotrexate with placebo in the treatment of systemic sclerosis: a 24 week randomized double-blind trial, followed by a 24 week observational trial. Br J Rheumatol 1996; 35(4):364-72
51. Pope JE, Bellamy N, Seibold JR, et al. A randomized, controlled trial of methotrexate versus placebo in early diffuse scleroderma. Arthritis Rheum 2001;44(6): 1351-8
52. Johnson SR, Feldman BM, Pope JE, Tomlinson GA. Shifting our thinking about uncommon disease trials: the case of methotrexate in scleroderma. J Rheumatol 2009;36(2):323-9
53. Rothenberg RJ, Graziano FM, Grandone JT, et al. The use of methotrexate in steroid resistant systemic lupus erythematosus. Arthritis Rheum 1988;31:612-15
54. Carneiro JRM, Sato EL. Double blind, randomized, placebo controlled clinical trial of methotrexate in systemic lupus erythematosus. J Rheumatol 1999;26: 1275-9
55. Islam MN, Hossain M, Haq SA, et al. Efficacy and safety of methotrexate in articular and cutaneous manifestations of systemic lupus erythematosus. Int J Rheum Dis 2012;15(1):62-8
56. Gansauge S, Breitbart A, Rinaldi N, Schwarz-Eywill M. Methotrexate in patients with moderate systemic lupus erythematosus (exclusion of renal and central nervous system disease). Ann Rheum Dis 1997;56: 382-5
57. Fortin PR, Abrahamowicz M, Ferland D, et al. Steroid-sparing effects of methotrexate in systemic lupus erythematosus: a double-blinded, randomized, placebo controlled trial. Arthritis Rheum 2008;59: 1796-804
58. Miyawaki S, Nishiyama S, Aita T, Yoshinaga Y. The effect of methotrexate on improving serological abnormalities of patients with systemic lupus erythematosus. Mod Rheumatol 2013;23(4):659-66.
59. Pego-Reigosa JM, Cobo-Ibáñez T, Calvo-Alén J, et al. Efficacy and safety of non-biologic immunusuppresants in the treatment of non-renal systemic lupus erythematosus: a systematic review. Arthritis Care Res (Hoboken) 2013. [Epub ahead of print]
60. Mahr AD, Jover JA, et al. Adjunctive methotrexate for treatment of giant cell arteritis: an individual patient data meta-analysis. Arthritis Rheum 2007;56: 2789-97
61. Mukhtyar C, Guillevin L, Cid MC. EULAR recommendations for the management of large vessel vasculitis. Ann Rheum Dis 2009;68:318-23
62. Spies CM, Burmester GR, Buttgereit F. Methotrexate treatment in large vessel vasculitis and polymyalgia rheumatic. Clin Exp Rheumatol 2010;28(5 Suppl 61): S172-7
63. Caporali R, Cimmino MA, et al. Prednisone plus methotrexate for polymyalgia rheumatica: a randomized, double-blind, placebo-controlled trial. Ann Intern Med 2004;141:493-500
64. Langford CA. Update on the treatment of granulomatosis with polyangiitis (Wegener's). Curr Treat Options Cardiovasc Med 2012;14(2):164-76
65. De Groot K, Rasmussen N, Bacon PA, et al. Randomized trial of cyclophosphamide versus methotrexate for induction of remission in early systemic antineutrophil cytoplasmic antibody-associated vasculitis. Arthritis Rheum 2005;52:2461-9
66. 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;42:2666-73
67. Langford CA, Talar-Williams C, Barron KS, et al. Use of a cyclophosphamide-induction methotrexate maintenance regimen for the treatment of Wegener's Update on the Treatment of Granulomatosis with Polyangiitis Langford 175 granulomatosis: extended follow-up and rate of relapse. Am J Med 2003;114:463-9
68. Pagnoux C, Mahr A, Hamidou MA, et al. Azathioprine or methotrexate maintenance for ANCA-associated vasculitis. N Engl J Med 2008;359:2790-803
69. Gerfaud-Valentin M, Jamilloux Y, Iwaz J, Sève P. Adult-onset Still's disease. Autoimmun Rev 2014;13:708-22
70. Fendler C1, Braun J. Use of methotrexate in inflammatory myopathies. Clin Exp Rheumatol 2010;28(5 Suppl 61):S164-7
71. Schiopu E, Phillips K, MacDonald PM, et al. Predictors of survival in a cohort of patients with polymyositis and dermatomyositis: effect of corticosteroids, methotrexate and azathioprine. Arthritis Res Ther 2012;14:R22
72. Buchner AM, Blonski W, Lichtenstein GR. Update on the management of Crohn's disease. Curr Gastroenterol Rep 2011;13(5): 465-74
73. Alfadhli AA, McDonald JW, Feagan BG. Methotrexate for induction of remission in refractory Crohn's disease. Cochrane Database Syst Rev 2005;CD003459
74. Feagan BG, Rochon J, Fedorak RN, et al. Methotrexate for the treatment of Crohn's disease. The North American Crohn's Study Group Investigators. N Engl J Med 1995; 332(5):292-7
75. 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(12):2203-9
76. Patel V, Macdonald JK, McDonald JW, et al. Methotrexate for maintenance of remission in Crohn's disease. Cochrane Database Syst Rev 2009;CD006884.
77. Feagan BG, Fedorak RN, Irvine EJ, et al. A comparison of methotrexate with placebo for the maintenance of remission in Crohn's disease. North American Crohn's Study Group Investigators. N Engl J Med 2000; 342(22):1627-32
78. Maté-Jiménez J, Hermida C, Cantero-Perona J, Moreno-Otero R. 6-Mercaptopurine or methotrexate added to prednisone induces and maintains remission in steroid dependent inflammatory bowel disease. Eur J Gastroenterol Hepatol 2000;12:1227-33
79. Swaminath A, Taunk R, Lawlor G. Use of methotrexate in inflammatory bowel disease in 2014: a User's Guide. World J Gastrointest Pharmacol Ther 2014;5:113-21
80. Khan N, Abbas AM, Moehlen M, Balart L. Methotrexate in ulcerative colitis: a nationwide retrospective cohort from the Veterans Affairs Health Care System. Inflamm Bowel Dis 2013;19:1379-83
81. van Ede AE, Laan RF, Blom HJ, et al. Methotrexate in rheumatoid arthritis: an update with focus on mechanisms involved in toxicity. Semin Arthritis Rheum 1998;27(5):277-92