Evidence-based use of methotrexate in children with rheumatic diseases: A consensus statement of the Working Groups Pediatric Rheumatology Germany (AGKJR) and Pediatric Rheumatology Austria

Rheumatology International

Volumn 25, Issue 3, 2005, Pages 169-178

  Niehues, Tim ^a   Horneff, Gerd ^b   Michels, Hartmut ^c   Höck, Michaela Sailer ^d   Schuchmann, Lothar ^e  

^a HEINRICH HEINE UNIVERSITY   (Germany)

^b MARTIN LUTHER UNIVERSITÄT HALLE WITTENBERG   (Germany)

^c Rheumatic Children's Hospital   (Germany)

^d ST ANNA CHILDREN S HOSPITAL   (Austria)

^e Working Group Pediatric Rheumatology   (Germany)

Author keywords

Children; Evidence based recommendations; Juvenile idiopathic arthritis; Methotrexate

Indexed keywords

ACICLOVIR; AZATHIOPRINE; BARBITURIC ACID DERIVATIVE; CELECOXIB; CHLOROQUINE; CORTICOSTEROID; COTRIMOXAZOLE; CYCLOSPORIN A; CYTOKINE RECEPTOR ANTAGONIST; DIMENHYDRINATE; ETANERCEPT; FOLIC ACID; HOMOCYSTEINE; METHOTREXATE; METOCLOPRAMIDE; NONSTEROID ANTIINFLAMMATORY AGENT; ONDANSETRON; ORAL CONTRACEPTIVE AGENT; PENICILLIN G; PHENYTOIN; PROBENECID; ROFECOXIB; SULFALAZINE; TETRACYCLINE; TRANQUILIZER; TROPISETRON; ANTIRHEUMATIC AGENT;

ABNORMALLY HIGH SUBSTRATE CONCENTRATION IN BLOOD; AUSTRIA; AVERSION; BLOOD TOXICITY; BONE MARROW APLASIA; BONE MARROW SUPPRESSION; CHICKENPOX; CLINICAL TRIAL; CONSENSUS; DISEASE PREDISPOSITION; DRUG ANTAGONISM; DRUG EFFICACY; DRUG POTENTIATION; DRUG SAFETY; EVIDENCE BASED MEDICINE; GASTROINTESTINAL TOXICITY; GERMANY; HODGKIN DISEASE; HUMAN; IMPOTENCE; INFECTION; JUVENILE RHEUMATOID ARTHRITIS; LEUKOPENIA; LIVER FIBROSIS; LIVER TOXICITY; LOW DRUG DOSE; LUNG FUNCTION TEST; MALFORMATION SYNDROME; MEDICAL RESEARCH; MEDICAL SOCIETY; MEDLINE; MEGALOCYTOSIS; NAUSEA; NEOPLASM; NEPHROTOXICITY; NEUTROPENIA; NONHODGKIN LYMPHOMA; OLIGOSPERMIA; PEDIATRICS; PNEUMONIA; PRACTICE GUIDELINE; PRIORITY JOURNAL; REGISTER; REVIEW; SIDE EFFECT; SKIN MANIFESTATION; SKIN TOXICITY; TERATOGENICITY; THROMBOCYTOPENIA; TREATMENT CONTRAINDICATION; ADOLESCENT; ARTICLE; CHILD; COMPARATIVE STUDY; DOSE RESPONSE; DRUG ADMINISTRATION; FEMALE; FOLLOW UP; HOSPITALIZATION; MALE; PRESCHOOL CHILD; RHEUMATIC DISEASE; RISK ASSESSMENT; TREATMENT OUTCOME;

ADOLESCENT; ANTIRHEUMATIC AGENTS; ARTHRITIS, JUVENILE RHEUMATOID; AUSTRIA; CHILD; CHILD, PRESCHOOL; DOSE-RESPONSE RELATIONSHIP, DRUG; DRUG ADMINISTRATION SCHEDULE; EVIDENCE-BASED MEDICINE; FEMALE; FOLLOW-UP STUDIES; HUMANS; MALE; METHOTREXATE; RHEUMATIC DISEASES; RISK ASSESSMENT; SEVERITY OF ILLNESS INDEX; TREATMENT OUTCOME;

EID: 17744384488     PISSN: 01728172     EISSN: None     Source Type: Journal    
DOI: 10.1007/s00296-004-0537-y     Document Type: Review

References (85)

1. Cassidy JT, Petty R (2001) Textbook of pediatric rheumatology, 4th edn. WB Saunders Company, Philadelphia
2. Wahn V, Oppermann J, Huppertz HI, Zepp F (2001) Rheumatische Erkrankungen im Kindes- und Jugendalter. Hans Marseille Verlag, Munich
3. Minden K, Niewerth M, Listing J, Zink A, German Study Group of Pediatric Rheumatologists (2002) Health care provision in pediatric rheumatology in Germany - national rheumatologic database. J Rheumatol 29(3):622-628
4. Olsen NJ, Murray LM (1989) Antiproliferative effects of methotrexate on peripheral blood mononuclear cells. Arthritis Rheum 32:378-385
5. Rosenblatt DS, Whitehead VM, Vera N, Pottier A, Dupont M, Vuchich MJ (1978) Prolonged inhibition of DNA synthesis associated with the accumulation of methotrexate polyglutamates by cultured human cells. Mol Pharmacol 14:1143-1147
6. Cutolo M, Sulli A, Pizzorni C, Seriolo B, Straub RH (2001) Anti-inflammatory mechanisms of methotrexate in rheumatoid arthritis. Ann Rheum Dis 60:729-735
7. Horneff G, Forster J, Seyberth HW, Michels H (2000) Recommendations by the Pediatric and Adolescent Rheumatology Study Committee on therapy with Etanercept (p75 TNF-alpha receptor immunoglobulin fusion protein, Pharmacotherapy Committee). Z Rheumatol 59:365-369
8. Onel KB (2000) Advances in the medical treatment of juvenile rheumatoid arthritis. Curr Opin Pediatr 12:72-75
9. Seeliger S, Niehues T, Harms E, Frosch M, Roth J (2002) Methotrexat in der Behandlung der juvenilen idiopathischen Arthritis. Monatsschr Kinderheilkd 150:452-459
10. Andersen PA, West SG, O'Dell JR, Via CS, Claypool RG, Kotzin BL (1985) Weekly pulse methotrexate in rheumatoid arthritis. Clinical and immunologic effects in a randomized, double-blind study. Ann Intern Med 103:489-496
11. Thompson RN, Watts C, Edelman J, Esdaile J, Russell AS (1984) A controlled two-centre trial of parenteral methotrexate therapy for refractory rheumatoid arthritis. J Rheumatol 11:760-763
12. Weinblatt ME, Coblyn JS, Fox DA, Fraser PA, Holdsworth DE, Glass DN, Trentham DE (1985) Efficacy of low-dose methotrexate in rheumatoid arthritis. N Engl J Med 312:818-822
13. Williams HJ, Willkens RF, Samuelson CO Jr, Alarcon GS, Guttadauria M, Yarboro C, Polisson RP, Weiner SR, Luggen ME, Billingsley LM et al (1985) Comparison of low-dose oral pulse methotrexate and placebo in the treatment of rheumatoid arthritis. A controlled clinical trial. Arthritis Rheum 28:721-730
14. Petty RE, Southwood TR, Baum J, Bhettay E, Glass DN, Manners P, Maldonado-Cocco J, Suarez-Almazor M, Orozco-Alcala J, Prieur AM (1998) Revision of the proposed classification criteria for juvenile idiopathic arthritis: Durban, 1997. J Rheumatol 25:1991-1994
15. Feldmann W (2000) Evidence-based pediatrics, 1st edn. BC Decker, Hamilton
16. Sackett DL, Rosenberg WM, Gray JA, Haynes RB, Richardson WS (1996) Evidence based medicine: what it is and what it isn't. BMJ 13:71-72
17. Truckenbrodt H, Hafner R (1986) Methotrexate therapy in juvenile rheumatoid arthritis: a retrospective study. Arthritis Rheum 29:801-807
18. Giannini EH, Brewer EJ, Kuzmina N, Shaikov A, Maximov A, Vorontsov I, Fink CW, Newman AJ, Cassidy JT, Zemel LS (1992) Methotrexate in resistant juvenile rheumatoid arthritis. Results of the U.S.A.-U.S.S.R. double-blind, placebo-controlled trial. The Pediatric Rheumatology Collaborative Study Group and The Cooperative Children's Study Group. N Engl J Med 326:1043-1049
19. Woo P, Southwood TR, Prieur AM, Dore CJ, Grainger J, David J, Ryder C, Hasson N, Hall A, Lemelle I (2000) Randomized, placebo-controlled, crossover trial of low-dose oral methotrexate in children with extended oligoarticular or systemic arthritis. Arthritis Rheum 43:1849-1857
20. Takken T, Van Der Net J, Helders PJ (2001) Methotrexate for treating juvenile idiopathic arthritis. Cochrane Database Syst Rev 4:CD003129
21. Ravelli A, Viola S, Migliavacca D, Ruperto N, Pistorio A, Martini A (1999) The extended oligoarticular subtype is the best predictor of methotrexate efficacy in juvenile idiopathic arthritis. J Pediatr 135:316-320
22. Cassidy JT (1999) Medical management of children with juvenile rheumatoid arthritis. Drugs 58:831-850
23. Ravelli A, Martini A (2000) Methotrexate in juvenile idiopathic arthritis: answers and questions. J Rheumatol 27:1830-1833
24. Breit W, Frosch M, Meyer U, Heinecke A, Ganser G (2000) A subgroup-specific evaluation of the efficacy of intraarticular triamcinolone hexacetonide in juvenile chronic arthritis. J Rheumatol 27:2696-2702
25. Padeh S, Passwell JH (1998) Intraarticular corticosteroid injection in the management of children with chronic arthritis. Arthritis Rheum 41:1210-1214
26. Ruperto N, Murray KJ, Gerloni V, Wulffraat N, De Oliveira S, Falcinin F, Alessio M, Burgos-Vargas R, Corona F, Vesely R, Foster H, Davidson J, Zulian F, Asplin L, Baildam E, Dolezalova P, Walsh J, Buoncompagni A, Garcia-Consuegra J, Ozdogan H, Saurenmann R, Joos R, Calvo I, Alpigiani LP, Machado C, Lahdenne P, Cortis E, Lepore L, Hall A, Kimura Y, Wouters C, Woo P, Martini A (2002) A randomized trial of Methotrexate in medium versus higher doses in children with juvenile idiopathic arthritis who failed on standard dose. In: EULAR Meeting Stockholm, Abstract Nr. 1384
27. Kremer JM, Galivan J, Streckfuss A, Kamen B (1986) Methotrexate metabolism analysis in blood and liver of rheumatoid arthritis patients. Association with hepatic folate deficiency and formation of polyglutamates. Arthritis Rheum 29:832-835
28. Ravelli A, Di Fuccia G, Molinaro M, Ramenghi B, Zonta L, Regazzi MB, Martini A (1993) Plasma levels after oral methotrexate in children with juvenile rheumatoid arthritis. J Rheumatol 20:1573-1577
29. Albertioni F, Flato B, Seideman P, Beck O, Vinje O, Peterson C, Eksborg S (1995) Methotrexate in juvenile rheumatoid arthritis. Evidence of age-dependent pharmacokinetics. Eur J Clin Pharmacol 47:507-511
30. Reiff A, Shaham B, Wood BP, Bernstein BH, Stanly P, Szer IS (1995) High dose methotrexate in the treatment of refractory juvenile rheumatoid arthritis. Clin Exp Rheumatol 13:113-118
31. Wallace CA, Bleyer WA, Sherry DD, Salmonson KL, Wedgwood RJ (1989) Toxicity and serum levels of methotrexate in children with juvenile rheumatoid arthritis. Arthritis Rheum 32:677-681
32. Oguey D, Kolliker F, Gerber NJ, Reichen J (1992) Effect of food on the bioavailability of low-dose methotrexate in patients with rheumatoid arthritis. Arthritis Rheum 35:611-614
33. Wallace CA (1998) The use of methotrexate in childhood rheumatic diseases. Arthritis Rheum 41:381-391
34. Balis FM, Mirro J Jr, Reaman GH, Evans WE, McCully C, Doherty KM, Murphy RF, Jeffries S, Poplack DG (1988) Pharmacokinetics of subcutaneous methotrexate. J Clin Oncol 6:1882-1886
35. Balis FM, Savitch JL, Bleyer WA (1983) Pharmacokinetics of oral methotrexate in children. Cancer Res 43:2342-2345
36. Jundt JW, Browne BA, Fiocco GP, Steele AD, Mock D (1993) A comparison of low dose methotrexate bioavailability: oral solution, oral tablet, subcutaneous and intramuscular dosing. J Rheumatol 20:1845-1849
37. Furst DE, Kremer JM (1988) Methotrexate in rheumatoid arthritis. Arthritis Rheum 31:305-314
38. Dupuis LL, Koren G, Silverman ED, Laxer RM (1995) Influence of food on the bioavailability of oral methotrexate in children. J Rheumatol 22:1570-1573
39. Morgan SL, Baggott JE, Lee JY, Alarcon GS (1998) Folic acid supplementation prevents deficient blood folate levels and hyperhomocysteinemia during longterm, low dose methotrexate therapy for rheumatoid arthritis: implications for cardiovascular disease prevention. J Rheumatol 25:441-446
40. van Ede AE, Laan RF, Blom HJ, Boers GH, Haagsma CJ, Thomas CM, De Boo TM, van de Putte LB (2002) Homocysteine and folate status in methotrexate-treated patients with rheumatoid arthritis (Oxford). Rheumatology 41:658-665
41. Ortiz Z, Shea B, Suarez-Almazor ME, Moher D, Wells GA, Tugwell P (1998) The efficacy of folic acid and folinic acid in reducing methotrexate gastrointestinal toxicity in rheumatoid arthritis. A metaanalysis of randomized controlled trials. J Rheumatol 25:36-43
42. van Ede AE, Laan RF, Rood MJ, Huizinga TW, van de Laar MA, van Denderen CJ, Westgeest TA, Romme TC, de Rooij DJ, Jacobs MJ, de Boo TM, van der Wilt GJ, Severens JL, Hartman M, Krabbe PF, Dijkmans BA, Breedveld FC, van de Putte LB (2001) Effect of folic or folinic acid supplementation on the toxicity and efficacy of methotrexate in rheumatoid arthritis: a forty-eight week, multicenter, randomized, double-blind, placebo-controlled study. Arthritis Rheum 44:1515-1524
43. Hunt PG, Rose CD, McIlvain-Simpson G, Tejani S (1997) The effects of daily intake of folic acid on the efficacy of methotrexate therapy in children with juvenile rheumatoid arthritis. A controlled study. J Rheumatol 24:2230-2232
44. Dupuis LL, Koren G, Shore A, Silverman ED, Laxer RM (1990) Methotrexate-nonsteroidal antiinflammatory drug interaction in children with arthritis. J Rheumatol 17:1469-1473
45. Singsen BH, Goldbach-Mansky R (1997) Methotrexate in the treatment of juvenile rheumatoid arthritis and other pediatric rheumatoid and nonrheumatic disorders. Rheum Dis Clin North Am 23:811-840
46. Wallace CA, Smith AL, Sherry DD (1993) Pilot investigation of naproxen/methotrexate interaction in patients with juvenile rheumatoid arthritis. J Rheumatol 20:1764-1768
47. Lafforgue P, Monjanel-Mouterde S, Durand A, Catalin J, Acquaviva PC (1993) Is there an interaction between low doses of corticosteroids and methotrexate in patients with rheumatoid arthritis? A pharmacokinetic study in 33 patients. J Rheumatol 20:263-267
48. O'Dell JR (2001) Combinations of conventional disease-modifying antirheumatic drugs. Rheum Dis Clin North Am 27:415-426
49. Barrera P, Haagsma CJ, Boerbooms AM, Van Riel PL, Borm GF, Van de Putte LB, Van der Meer JW (1995) Effect of methotrexate alone or in combination with sulphasalazine on the production and circulating concentrations of cytokines and their antagonists. Longitudinal evaluation in patients with rheumatoid arthritis. Br J Rheumatol 34:747-755
50. Seitz M, Loetscher P, Dewald B, Towbin H, Rordorf C, Gallati H, Baggiolini M, Gerber NJ (1995) Methotrexate action in rheumatoid arthritis: stimulation of cytokine inhibitor and inhibition of chemokine production by peripheral blood mononuclear cells. Br J Rheumatol 34:602-609
51. Weinblatt ME, Kremer JM, Bankhurst AD, Bulpitt KJ, Fleischmann RM, Fox RI, Jackson CG, Lange M, Burge DJ (1999) A trial of etanercept, a recombinant tumor necrosis factor receptor:Fc fusion protein, in patients with rheumatoid arthritis receiving methotrexate. N Engl J Med 340:253-259
52. Schmeling H, Mathony K, John V, Keysser G, Burdach S, Horneff G (2001) A combination of etanercept and methotrexate for the treatment of refractory juvenile idiopathic arthritis: a pilot study. Ann Rheum Dis 60:410-412
53. Graham LD, Myones BL, Rivas-Chacon RF, Pachman LM (1992) Morbidity associated with long-term methotrexate therapy in juvenile rheumatoid arthritis. J Pediatr 120:468-473
54. Grennan DM, Gray J, Loudon J, Fear S (2001) Methotrexate and early postoperative complications in patients with rheumatoid arthritis undergoing elective orthopaedic surgery. Ann Rheum Dis 60:214-217
55. Franke J, Hafner R, Lohrs U, Truckenbrodt H (1996) Methotrexate and liver fibrosis in juvenile chronic arthritis retrospective study of 73 liver biopsies. Monatsschrift Kinderheilkunde 144:147-151
56. Hashkes PJ, Balistreri WF, Bove KE, Ballard ET, Passo MH (1997) The long-term effect of methotrexate therapy on the liver in patients with juvenile rheumatoid arthritis. Arthritis Rheum 40:2226-2234
57. Erickson AR, Reddy V, Vogelgesang SA, West SG (1995) Usefulness of the American College of Rheumatology recommendations for liver biopsy in methotrexate-treated rheumatoid arthritis patients. Arthritis Rheum 38:1115-1119
58. Kremer JM, Alarcon GS, Lightfoot RW Jr, Willkens RF, Furst DE, Williams HJ, Dent PB, Weinblatt ME (1994) Methotrexate for rheumatoid arthritis. Suggested guidelines for monitoring liver toxicity. American College of Rheumatology. Arthritis Rheum 37:316-328
59. McKendry RJ (1997) The remarkable spectrum of methotrexate toxicities. Rheum Dis Clin North Am 23:939-954
60. Kremer JM, Alarcon GS, Weinblatt ME, Kaymakcian MV, Macaluso M, Cannon GW, Palmer WR, Sundy JS, St Clair EW, Alexander RW, Smith GJ, Axiotis CA (1997) Clinical, laboratory, radiographic, and histopathologic features of methotrexate-associated lung injury in patients with rheumatoid arthritis: a multicenter study with literature review. Arthritis Rheum 40:1829-1837
61. Salaffi F, Manganelli P, Carotti M, Subiaco S, Lamanna G, Cervini C (1997) Methotrexate-induced pneumonitis in patients with rheumatoid arthritis and psoriatic arthritis: report of five cases and review of the literature. Clin Rheumatol 16:296-304
62. Cron RQ, Sherry DD, Wallace CA (1998) Methotrexate-induced hypersensitivity pneumonitis in a child with juvenile rheumatoid arthritis. J Pediatr 132:901-902
63. Camiciottoli G, Trapani S, Castellani W, Ginanni R, Ermini M, Falcini F (1998) Effect on lung function of methotrexate and non-steroid anti-inflammatory drugs in children with juvenile rheumatoid arthritis. Rheumatol Int 18:11-16
64. Pelucchi A, Lomater C, Gerloni V, Foresi A, Fantini F, Marazzini L (1994) Lung function and diffusing capacity for carbon monoxide in patients with juvenile chronic arthritis: effect of disease activity and low dose methotrexate therapy. Clin Exp Rheumatol 12:675-679
65. Schmeling H, Stephan V, Burdach S, Horneff G (2002) Pulmonary function in children with juvenile idiopathic arthritis and effects of methotrexate therapy. Z Rheumatol 61:168-172
66. Mariette X, Cazals-Hatem D, Warszawki J, Liote F, Balandraud N, Sibilia J (2002) Lymphomas in rheumatoid arthritis patients treated with methotrexate: a 3-year prospective study in France. Blood 1(99):3909-3915
67. Rau R (1994) Treatment of chronic polyarthritis with methotrexate 1994 - a review. Z Rheumatol 53:199-229
68. Cleary AG, McDowell H, Sills JA (2002) Polyarticular juvenile idiopathic arthritis treated with methotrexate complicated by the development of non-Hodgkin's lymphoma. Arch Dis Child 86:47-49
69. Krugmann J, Sailer-Hock M, Muller T, Gruber J, Allerberger F, Offner FA (2000) Epstein-Barr virus-associated Hodgkin's lymphoma and Legionella pneumophila infection complicating treatment of juvenile rheumatoid arthritis with methotrexate and cyclosporine A. Hum Pathol 31:253-255
70. Londino AV Jr, Blatt J, Knisely AS (1998) Hodgkin's disease in a patient with juvenile rheumatoid arthritis taking weekly low dose methotrexate. J Rheumatol 25:1245-1246
71. Munro R, Porter DR, Sturrock RD (1998) Lymphadenopathy in a patient with systemic onset juvenile chronic arthritis. Ann Rheum Dis 57:513-517
72. Padeh S, Sharon N, Schiby G, Rechavi G, Passwell JH (1997) Hodgkin's lymphoma in systemic onset juvenile rheumatoid arthritis after treatment with low dose methotrexate. J Rheumatol 24:2035-2037
73. Bawle EV, Conard JV, Weiss L (1998) Adult and two children with fetal methotrexate syndrome. Teratology 57:51-55
74. Kozlowski RD, Steinbrunner JV, MacKenzie AH, Clough JD, Wilke WS, Segal AM (1990) Outcome of first-trimester exposure to low-dose methotrexate in eight patients with rheumatic disease. Am J Med 88:589-592
75. Buckley LM, Bullaboy CA, Leichtman L, Marquez M (1997) Multiple congenital anomalies associated with weekly low-dose methotrexate treatment of the mother. Arthritis Rheum 40:971-973
76. Blackburn WD Jr, Alarcon GS (1989) Impotence in three rheumatoid arthritis patients treated with methotrexate. Arthritis Rheum 32:1341-1342
77. Sussman A, Leonard JM (1980) Psoriasis, methotrexate, and oligospermia. Arch Dermatol 116:215-217
78. O'Dell JR (1997) Methotrexate use in rheumatoid arthritis. Rheum Dis Cl N Am 23:779-796
79. Aherne GW, Piall E, Marks V, Mould G, White WF (1978) Prolongation and enhancement of serum methotrexate concentrations by probenecid. Br Med J 29:1097-1099
80. Brik R, Berkowitz D, Berant M (1998) Duration of methotrexate treatment until partial and total remission of refractory juvenile rheumatoid arthritis. Ann Rheum Dis 57:174-175
81. Huang JL (1996) Methotrexate in the treatment of children with chronic arthritis-long-term observations of efficacy and safety. Br J Clin Pract 50:311-314
82. Gottlieb BS, Keenan GF, Lu T, Ilowite NT (1997) Discontinuation of methotrexate treatment in juvenile rheumatoid arthritis. Pediatrics 100:994-997
83. Ravelli A, Viola S, Ramenghi B, Aramini L, Ruperto N, Martini A (1995) Frequency of relapse after discontinuation of methotrexate therapy for clinical remission in juvenile rheumatoid arthritis. J Rheumatol 22:1574-1576
84. Huemer M, Fodinger M, Huemer C, Sailer-Hock M, Falger J, Rettenbacher A, Bernecker M, Artacker G, Kenzian H, Lang T, Stockler-Ipsiroglu S (2003) Hyperhomocysteinemia in children with juvenile idiopathic arthritis is not influenced by methotrexate treatment and folic acid supplementation: a pilot study. Clin Exp Rheumatol 21:249-255
85. Foell D, Frosch M, Schulze zur Wiesch A, Vogl T, Sorg C, Roth J (2004) Methotrexate treatment in juvenile idiopathic arthritis: when is the right time to stop? Ann Rheum Dis 63:206-208