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Published in: Pediatric Drugs 6/2006

01-11-2006 | Therapy In Practice

Recommendations for the Use of Methotrexate in Juvenile Idiopathic Arthritis

Authors: Dr Tim Niehues, Petra Lankisch

Published in: Pediatric Drugs | Issue 6/2006

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Abstract

Juvenile idiopathic arthritis (JIA) is one of the most common rheumatic diseases in childhood. In a significant number of JIA cases the disease is resistant to therapy with NSAIDs, intra-articular corticosteroid injections, and physiotherapy, and methotrexate is used as a second-line agent. The efficacy of methotrexate therapy in children with JIA has been demonstrated in prospective controlled trials and this agent appears to have slightly superior efficacy compared with leflunomide. Data from randomized studies indicate a starting dose of 10–15 mg/m2/week orally. The dose of parenteral methotrexate can be increased to 15–20 mg/m2/week. Combination therapy with methotrexate and an NSAID is recommended. However, there are still no data on when to initiate methotrexate in JIA and how long children should be treated.
The most common adverse effects are aversion to the drug and nausea. In the case of minor adverse effects the use of folic acid at a dosage of 1 mg/day is feasible. In JIA, daily folate supplementation has only been studied in one small heterogeneous cohort with a very short observation period and, at present, a general recommendation on daily folate supplementation cannot be made.
In summary, methotrexate is seen by many pediatric rheumatologists as the first-choice, second-line drug; there is good evidence of its efficacy in JIA. However, in light of the recent introduction of biologic agents, the place of methotrexate in the treatment of JIA may have to be redefined in the coming years.
Literature
1.
go back to reference Cassidy JT, Petty R. Textbook of pediatric rheumatology. 4th ed. Philadelphia (PA): WB Saunders Company, 2001 Cassidy JT, Petty R. Textbook of pediatric rheumatology. 4th ed. Philadelphia (PA): WB Saunders Company, 2001
2.
go back to reference Wahn V, Oppermann J, Huppertz HI, et al. Rheumatische Erkrankungen im Kindes- und Jugendalter. Hans Marseille Verlag 2001; 1: 156 Wahn V, Oppermann J, Huppertz HI, et al. Rheumatische Erkrankungen im Kindes- und Jugendalter. Hans Marseille Verlag 2001; 1: 156
3.
go back to reference Minden K, Niewerth M, Listing J, et al. German Study Group of Pediatric Rheumatologists: health care provision in pediatric rheumatology in Germany: national rheumatologic database. J Rheumatol 2002 Mar; 29(3): 622–8PubMed Minden K, Niewerth M, Listing J, et al. German Study Group of Pediatric Rheumatologists: health care provision in pediatric rheumatology in Germany: national rheumatologic database. J Rheumatol 2002 Mar; 29(3): 622–8PubMed
4.
go back to reference Foeldvari I, Wierk A. Methotrexate is an effective treatment for chronic uveitis associated with juvenile idiopathic arthritis. J Rheumatol 2005 Feb; 32: 362–5PubMed Foeldvari I, Wierk A. Methotrexate is an effective treatment for chronic uveitis associated with juvenile idiopathic arthritis. J Rheumatol 2005 Feb; 32: 362–5PubMed
5.
go back to reference Ramanan AV, Withworth P, Baildam EM. Use of methotrexate in juvenile idiopathic arthritis. Arch Dis Child 2003; 88: 197–200PubMedCrossRef Ramanan AV, Withworth P, Baildam EM. Use of methotrexate in juvenile idiopathic arthritis. Arch Dis Child 2003; 88: 197–200PubMedCrossRef
6.
7.
go back to reference Hou Z, Stapels SE, Haska CL, et al. Localization of a substrate binding domain of the human reduced folate carrier to transmembrane domain 11 by radioaffinity labeling and cysteine-substituted accessibility methods. J Biol Chem 2005; 280: 36206–13PubMedCrossRef Hou Z, Stapels SE, Haska CL, et al. Localization of a substrate binding domain of the human reduced folate carrier to transmembrane domain 11 by radioaffinity labeling and cysteine-substituted accessibility methods. J Biol Chem 2005; 280: 36206–13PubMedCrossRef
8.
go back to reference Dolezalova P, Krijt J, Chladek J, et al. Adenosine and methotrexate polyglutamate concentrations in patients with juvenile arthritis. Rheumatology 2005; 44: 74–9PubMedCrossRef Dolezalova P, Krijt J, Chladek J, et al. Adenosine and methotrexate polyglutamate concentrations in patients with juvenile arthritis. Rheumatology 2005; 44: 74–9PubMedCrossRef
9.
go back to reference Johnston A, Gudjonsson JE, Sigmundsdottir H, et al. The anti-inflammatory action of methotrexate is not mediated by lymphocyte apoptosis, but by the suppression of activation and adhesion molecules. Clin Immunol 2005; 114: 154–63PubMedCrossRef Johnston A, Gudjonsson JE, Sigmundsdottir H, et al. The anti-inflammatory action of methotrexate is not mediated by lymphocyte apoptosis, but by the suppression of activation and adhesion molecules. Clin Immunol 2005; 114: 154–63PubMedCrossRef
10.
go back to reference Onel KB. Advances in the medical treatment of juvenile rheumatoid arthritis. Curr Opin Pediatr 2000; 12: 72–5PubMedCrossRef Onel KB. Advances in the medical treatment of juvenile rheumatoid arthritis. Curr Opin Pediatr 2000; 12: 72–5PubMedCrossRef
11.
go back to reference Seeliger S, Niehues T, Harms E, et al. Methotrexate in der Behandlung der juvenilen idiopathischen arthritis. Monatsschr Kinderheilkd 2002; 150: 452–9CrossRef Seeliger S, Niehues T, Harms E, et al. Methotrexate in der Behandlung der juvenilen idiopathischen arthritis. Monatsschr Kinderheilkd 2002; 150: 452–9CrossRef
12.
go back to reference Niehues T, Horneff G, Michels H, et al. 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. Rheumatol Int 2005; 25: 169–78PubMedCrossRef Niehues T, Horneff G, Michels H, et al. 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. Rheumatol Int 2005; 25: 169–78PubMedCrossRef
13.
go back to reference Andersen PA, West SG, O’Dell JR, et al. Weekly pulse methotrexate in rheumatoid arthritis: clinical and immunologic effects in a randomized, double-blind study. Ann Intern Med 1985; 103: 489–96PubMed Andersen PA, West SG, O’Dell JR, et al. Weekly pulse methotrexate in rheumatoid arthritis: clinical and immunologic effects in a randomized, double-blind study. Ann Intern Med 1985; 103: 489–96PubMed
14.
go back to reference Thompson RN, Watts C, Edelman J, et al. A controlled two-centre trial of parenteral methotrexate therapy for refractory rheumatoid arthritis. J Rheumatol 1984; 11: 760–3PubMed Thompson RN, Watts C, Edelman J, et al. A controlled two-centre trial of parenteral methotrexate therapy for refractory rheumatoid arthritis. J Rheumatol 1984; 11: 760–3PubMed
15.
go back to reference Weinblatt ME, Coblyn JS, Fox DA, et al. Efficacy of low-dose methotrexate in rheumatoid arthritis. N Engl J Med 1985; 312: 818–22PubMedCrossRef Weinblatt ME, Coblyn JS, Fox DA, et al. Efficacy of low-dose methotrexate in rheumatoid arthritis. N Engl J Med 1985; 312: 818–22PubMedCrossRef
16.
go back to reference Williams HJ, Willkens RF, Samuelson Jr CO, 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: 721–30PubMedCrossRef Williams HJ, Willkens RF, Samuelson Jr CO, 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: 721–30PubMedCrossRef
17.
go back to reference Canadian Task Force on the Periodic Health Examination. Canadian guide to clinical preventive health care. Ottawa (ON): Canada Communication Group, 1994 Canadian Task Force on the Periodic Health Examination. Canadian guide to clinical preventive health care. Ottawa (ON): Canada Communication Group, 1994
18.
go back to reference U.S. Preventive Services Task Force. Guide to clinical preventive services. 2nd ed. Baltimore (MD): Williams and Wilkins, 1996 U.S. Preventive Services Task Force. Guide to clinical preventive services. 2nd ed. Baltimore (MD): Williams and Wilkins, 1996
19.
go back to reference Feldmann W. Evidence-based pediatrics. 1st ed. Hamilton (ON): BC Decker, 2000 Feldmann W. Evidence-based pediatrics. 1st ed. Hamilton (ON): BC Decker, 2000
20.
go back to reference Sackett DL, Rosenberg WM, Gray JA, et al. Evidence based medicine: what it is and what it isn’t. BMJ 1996; 13: 71–2CrossRef Sackett DL, Rosenberg WM, Gray JA, et al. Evidence based medicine: what it is and what it isn’t. BMJ 1996; 13: 71–2CrossRef
21.
go back to reference Truckenbrodt H, Hafner R. Methotrexate therapy in juvenile rheumatoid arthritis: a retrospective study. Arthritis Rheum 1986; 29: 801–7PubMedCrossRef Truckenbrodt H, Hafner R. Methotrexate therapy in juvenile rheumatoid arthritis: a retrospective study. Arthritis Rheum 1986; 29: 801–7PubMedCrossRef
22.
go back to reference Giannini EH, Cassidy JT, Brewer EJ, et al. Comparative efficacy and safety of advanced drug therapy in children with juvenile rheumatoid arthritis. Semin Arthritis Rheum 1993 Aug; 23: 34–46PubMedCrossRef Giannini EH, Cassidy JT, Brewer EJ, et al. Comparative efficacy and safety of advanced drug therapy in children with juvenile rheumatoid arthritis. Semin Arthritis Rheum 1993 Aug; 23: 34–46PubMedCrossRef
23.
go back to reference Giannini EH, Brewer EJ, Kuzmina N, et al. Methotrexate in resistant juvenile rheumatoid arthritis: results of the USA-USSR double-blind, placebo-controlled trial. The Pediatric Rheumatology Collaborative Study Group and the Cooperative Children’s Study Group. N Engl J Med 1992; 326: 1043–9PubMedCrossRef Giannini EH, Brewer EJ, Kuzmina N, et al. Methotrexate in resistant juvenile rheumatoid arthritis: results of the USA-USSR double-blind, placebo-controlled trial. The Pediatric Rheumatology Collaborative Study Group and the Cooperative Children’s Study Group. N Engl J Med 1992; 326: 1043–9PubMedCrossRef
24.
go back to reference Woo P, Southwood TR, Prieur AM, et al. Randomized, placebo-controlled, crossover trial of low-dose oral methotrexate in children with extended oligoarticular or systemic arthritis. Arthritis Rheum 2000; 43: 1849–57PubMedCrossRef Woo P, Southwood TR, Prieur AM, et al. Randomized, placebo-controlled, crossover trial of low-dose oral methotrexate in children with extended oligoarticular or systemic arthritis. Arthritis Rheum 2000; 43: 1849–57PubMedCrossRef
25.
go back to reference Takken T, Van der Net J, Helder PJ. Methotrexate for treating juvenile idiopathic arthritis. Cochrane Database Syst Rev 2001; (4): CD003129 Takken T, Van der Net J, Helder PJ. Methotrexate for treating juvenile idiopathic arthritis. Cochrane Database Syst Rev 2001; (4): CD003129
26.
go back to reference Ravelli A, Viola S, Migliavacca D, et al. The extended oligoarticular subtype is the best predictor of methotrexate efficacy in juvenile idiopathic arthritis. J Pediatr 1999; 135: 316–20PubMedCrossRef Ravelli A, Viola S, Migliavacca D, et al. The extended oligoarticular subtype is the best predictor of methotrexate efficacy in juvenile idiopathic arthritis. J Pediatr 1999; 135: 316–20PubMedCrossRef
27.
go back to reference Silverman E, Spiegel L, Hawkins D, et al. Leflunomide or methotrexate for juvenile rheumatoid arthritis. N Engl J Med 2005 Apr; 352: 1655–66PubMedCrossRef Silverman E, Spiegel L, Hawkins D, et al. Leflunomide or methotrexate for juvenile rheumatoid arthritis. N Engl J Med 2005 Apr; 352: 1655–66PubMedCrossRef
28.
go back to reference Cassidy JT. Medical management of children with juvenile rheumatoid arthritis. Drugs 1999; 58: 831–50PubMedCrossRef Cassidy JT. Medical management of children with juvenile rheumatoid arthritis. Drugs 1999; 58: 831–50PubMedCrossRef
29.
go back to reference Ravelli A, Martini A. Methotrexate in juvenile idiopathic arthritis: answers and questions. J Rheumatol 2000; 27: 1830–3PubMed Ravelli A, Martini A. Methotrexate in juvenile idiopathic arthritis: answers and questions. J Rheumatol 2000; 27: 1830–3PubMed
30.
go back to reference Breit W, Frosch M, Meyer U, et al. A subgroup-specific evaluation of the efficacy of intraarticular triamcinolone hexacetonide in juvenile chronic arthritis. J Rheumatol 2000; 27: 2696–702PubMed Breit W, Frosch M, Meyer U, et al. A subgroup-specific evaluation of the efficacy of intraarticular triamcinolone hexacetonide in juvenile chronic arthritis. J Rheumatol 2000; 27: 2696–702PubMed
31.
go back to reference Padeh S, Passwell JH. Intraarticular corticosteroid injection in the management of children with chronic arthritis. Arthritis Rheum 1998; 41: 1210–4PubMedCrossRef Padeh S, Passwell JH. Intraarticular corticosteroid injection in the management of children with chronic arthritis. Arthritis Rheum 1998; 41: 1210–4PubMedCrossRef
32.
go back to reference Brik R, Berkowitz D, Berant M. Duration of methotrexate treatment until partial and total remission of refractory juvenile rheumatoid arthritis. Ann Rheum Dis 1998; 57: 174–5PubMedCrossRef Brik R, Berkowitz D, Berant M. Duration of methotrexate treatment until partial and total remission of refractory juvenile rheumatoid arthritis. Ann Rheum Dis 1998; 57: 174–5PubMedCrossRef
33.
go back to reference Huang JL. Methotrexate in the treatment of children with chronic arthritis: long-term observations of efficacy and safety. Br J Clin Pract 1996; 50: 311–4PubMed Huang JL. Methotrexate in the treatment of children with chronic arthritis: long-term observations of efficacy and safety. Br J Clin Pract 1996; 50: 311–4PubMed
34.
go back to reference Gottlieb BS, Keenan GF, Lu T, et al. Discontinuation of methotrexate treatment in juvenile rheumatoid arthritis. Pediatrics 1997; 100: 994–7PubMedCrossRef Gottlieb BS, Keenan GF, Lu T, et al. Discontinuation of methotrexate treatment in juvenile rheumatoid arthritis. Pediatrics 1997; 100: 994–7PubMedCrossRef
35.
go back to reference Ravelli A, Viola S, Ramenghi B, et al. Frequency of relapse after discontinuation of methotrexate therapy for clinical remission in juvenile rheumatoid arthritis. J Rheumatol 1995; 22: 1574–6PubMed Ravelli A, Viola S, Ramenghi B, et al. Frequency of relapse after discontinuation of methotrexate therapy for clinical remission in juvenile rheumatoid arthritis. J Rheumatol 1995; 22: 1574–6PubMed
36.
go back to reference Foell D, Frosch M, Schulze zur Wiesch A, et al. Methotrexate treatment in juvenile idiopathic arthritis: when is the right time to stop? Ann Rheum Dis 2004; 63: 206–8PubMedCrossRef Foell D, Frosch M, Schulze zur Wiesch A, et al. Methotrexate treatment in juvenile idiopathic arthritis: when is the right time to stop? Ann Rheum Dis 2004; 63: 206–8PubMedCrossRef
37.
go back to reference Ruperto N, Murray KJ, Gerloni V, et al. A randomized trial of methotrexate comparing an intermediate dose with a higher dose in children with juvenile idiopathic arthritis who failed to respond to standard doses of methotrexate. Arthritis Rheum 2004 Jul; 50: 2192–202CrossRef Ruperto N, Murray KJ, Gerloni V, et al. A randomized trial of methotrexate comparing an intermediate dose with a higher dose in children with juvenile idiopathic arthritis who failed to respond to standard doses of methotrexate. Arthritis Rheum 2004 Jul; 50: 2192–202CrossRef
38.
go back to reference Kremer JM, Galivan J, Streckfuss A, et al. Methotrexate metabolism analysis in blood and liver of rheumatoid arthritis patients: association with hepatic folate deficiency and formation of polyglutamates. Arthritis Rheum 1986; 29: 832–5PubMedCrossRef Kremer JM, Galivan J, Streckfuss A, et al. Methotrexate metabolism analysis in blood and liver of rheumatoid arthritis patients: association with hepatic folate deficiency and formation of polyglutamates. Arthritis Rheum 1986; 29: 832–5PubMedCrossRef
39.
go back to reference Oguey D, Kolliker F, Gerber NJ, et al. Effect of food on the bioavailability of low-dose methotrexate in patients with rheumatoid arthritis. Arthritis Rheum 1992; 35: 611–4PubMedCrossRef Oguey D, Kolliker F, Gerber NJ, et al. Effect of food on the bioavailability of low-dose methotrexate in patients with rheumatoid arthritis. Arthritis Rheum 1992; 35: 611–4PubMedCrossRef
40.
go back to reference Wallace CA. The use of methotrexate in childhood rheumatic diseases. Arthritis Rheum 1998; 41: 381–91PubMedCrossRef Wallace CA. The use of methotrexate in childhood rheumatic diseases. Arthritis Rheum 1998; 41: 381–91PubMedCrossRef
41.
go back to reference Balis FM, Mirro Jr J, Reaman GH, et al. Pharmacokinetics of subcutaneous methotrexate. J Clin Oncol 1988; 6: 1882–6PubMed Balis FM, Mirro Jr J, Reaman GH, et al. Pharmacokinetics of subcutaneous methotrexate. J Clin Oncol 1988; 6: 1882–6PubMed
42.
go back to reference Balis FM, Savitch JL, Bleyer WA. Pharmacokinetics of oral methotrexate in children. Cancer Res 1983; 43: 2342–5PubMed Balis FM, Savitch JL, Bleyer WA. Pharmacokinetics of oral methotrexate in children. Cancer Res 1983; 43: 2342–5PubMed
43.
go back to reference Alsufyani K, Ortiz-Alvarez O, Cabral DA, et al. The role of subcutaneous administration of methotrexate in children with juvenile idiopathic arthritis who have failed oral methotrexate. J Rheumatol 2004; 31: 179–82PubMed Alsufyani K, Ortiz-Alvarez O, Cabral DA, et al. The role of subcutaneous administration of methotrexate in children with juvenile idiopathic arthritis who have failed oral methotrexate. J Rheumatol 2004; 31: 179–82PubMed
44.
go back to reference Jundt JW, Browne BA, Fiocco GP, et al. A comparison of low dose methotrexate bioavailability: oral solution, oral tablet, subcutaneous and intramuscular dosing. J Rheumatol 1993; 20: 1845–9PubMed Jundt JW, Browne BA, Fiocco GP, et al. A comparison of low dose methotrexate bioavailability: oral solution, oral tablet, subcutaneous and intramuscular dosing. J Rheumatol 1993; 20: 1845–9PubMed
45.
46.
go back to reference Dupuis LL, Koren G, Silverman ED, et al. Influence of food on the bioavailability of oral methotrexate in children. J Rheumatol 1995; 22: 1570–3PubMed Dupuis LL, Koren G, Silverman ED, et al. Influence of food on the bioavailability of oral methotrexate in children. J Rheumatol 1995; 22: 1570–3PubMed
47.
48.
go back to reference Aherne GW, Piall E, Marks V, et al. Prolongation and enhancement of serum methotrexate concentrations by probenecid. BMJ 1978; 29: 1097–9CrossRef Aherne GW, Piall E, Marks V, et al. Prolongation and enhancement of serum methotrexate concentrations by probenecid. BMJ 1978; 29: 1097–9CrossRef
49.
go back to reference Albertioni F, Flato B, Seideman P, et al. Methotrexate in juvenile rheumatoid arthritis: evidence of age dependent pharmacokinetics. Eur J Clin Pharmacol 1995; 47: 507–11PubMedCrossRef Albertioni F, Flato B, Seideman P, et al. Methotrexate in juvenile rheumatoid arthritis: evidence of age dependent pharmacokinetics. Eur J Clin Pharmacol 1995; 47: 507–11PubMedCrossRef
50.
go back to reference Reiff A, Shaham B, Wood BP, et al. High dose methotrexate in the treatment of refractory juvenile rheumatoid arthritis. Clin Exp Rheumatol 1995; 13: 113–8PubMed Reiff A, Shaham B, Wood BP, et al. High dose methotrexate in the treatment of refractory juvenile rheumatoid arthritis. Clin Exp Rheumatol 1995; 13: 113–8PubMed
51.
go back to reference Wallace CA, Bleyer WA, Sherry DD, et al. Toxicity and serum levels of methotrexate in children with juvenile rheumatoid arthritis. Arthritis Rheum 1989; 32: 677–81PubMedCrossRef Wallace CA, Bleyer WA, Sherry DD, et al. Toxicity and serum levels of methotrexate in children with juvenile rheumatoid arthritis. Arthritis Rheum 1989; 32: 677–81PubMedCrossRef
52.
go back to reference Morgan SL, Oster RA, Lee JY, et al. The effect of folic acid and folinic acid supplementation on purine metabolism in methotrexate-treated rheumatoid arthritis. Arthritis Rheum 2004; 50: 3104–11PubMedCrossRef Morgan SL, Oster RA, Lee JY, et al. The effect of folic acid and folinic acid supplementation on purine metabolism in methotrexate-treated rheumatoid arthritis. Arthritis Rheum 2004; 50: 3104–11PubMedCrossRef
53.
go back to reference Cronstein BN. Folic acid and folinic acid supplements and methotrexate therapy: comment on the article by Morgan, et al. Arthritis Rheum 2005 Apr; 52(4): 1338–9PubMedCrossRef Cronstein BN. Folic acid and folinic acid supplements and methotrexate therapy: comment on the article by Morgan, et al. Arthritis Rheum 2005 Apr; 52(4): 1338–9PubMedCrossRef
54.
go back to reference 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 metaanalysis of randomized controlled trials. J Rheumatol 1998; 25: 36–43PubMed 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 metaanalysis of randomized controlled trials. J Rheumatol 1998; 25: 36–43PubMed
55.
go back to reference van Ede AE, Laan RF, Rood MJ, et al. 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 2001; 44: 1515–24PubMedCrossRef van Ede AE, Laan RF, Rood MJ, et al. 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 2001; 44: 1515–24PubMedCrossRef
56.
go back to reference Morgan SL, Baggott JE, Lee JY, et al. Folic acid supplementation prevents deficient blood folate levels and hyperhomocysteinemia during long term, low dose methotrexate therapy for rheumatoid arthritis: implications for cardiovascular disease prevention. J Rheumatol 1998; 25: 441–6PubMed Morgan SL, Baggott JE, Lee JY, et al. Folic acid supplementation prevents deficient blood folate levels and hyperhomocysteinemia during long term, low dose methotrexate therapy for rheumatoid arthritis: implications for cardiovascular disease prevention. J Rheumatol 1998; 25: 441–6PubMed
57.
go back to reference van Ede AE, Laan RF, Blom HJ, et al. Homocysteine and folate status in methotrexate-treated patients with rheumatoid arthritis. Rheumatol (Oxf) 2002; 41: 658–65CrossRef van Ede AE, Laan RF, Blom HJ, et al. Homocysteine and folate status in methotrexate-treated patients with rheumatoid arthritis. Rheumatol (Oxf) 2002; 41: 658–65CrossRef
58.
59.
go back to reference Hunt PG, Rose CD, McIlvain-Simpson G, et al. 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 1997; 24: 2230–2PubMed Hunt PG, Rose CD, McIlvain-Simpson G, et al. 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 1997; 24: 2230–2PubMed
60.
go back to reference Huemer M, Fodinger M, Huemer C, et al. Hyperhomocysteinemia in children with juvenile idiopathic arthritis is not influenced by methotrexate treatment and folic acid supplementation: a pilot study. Clin Exp Rheumatol 2003; 21: 249–55PubMed Huemer M, Fodinger M, Huemer C, et al. Hyperhomocysteinemia in children with juvenile idiopathic arthritis is not influenced by methotrexate treatment and folic acid supplementation: a pilot study. Clin Exp Rheumatol 2003; 21: 249–55PubMed
61.
go back to reference Dupuis LL, Koren G, Shore A, et al. Methotrexate-nonsteroidal antiinflammatory drug interaction in children with arthritis. J Rheumatol 1990; 17: 1469–73PubMed Dupuis LL, Koren G, Shore A, et al. Methotrexate-nonsteroidal antiinflammatory drug interaction in children with arthritis. J Rheumatol 1990; 17: 1469–73PubMed
62.
go back to reference Singsen BH, Goldbach-Mansky R. Methotrexate in the treatment of juvenile rheumatoid arthritis and other pediatric rheumatoid and nonrheumatic disorders. Rheum Dis Clin North Am 1997; 23: 811–40PubMedCrossRef Singsen BH, Goldbach-Mansky R. Methotrexate in the treatment of juvenile rheumatoid arthritis and other pediatric rheumatoid and nonrheumatic disorders. Rheum Dis Clin North Am 1997; 23: 811–40PubMedCrossRef
63.
go back to reference Wallace CA, Smith AL, Sherry DD. Pilot investigation of naproxen/methotrexate interaction in patients with juvenile rheumatoid arthritis. J Rheumatol 1993; 20: 1764–8PubMed Wallace CA, Smith AL, Sherry DD. Pilot investigation of naproxen/methotrexate interaction in patients with juvenile rheumatoid arthritis. J Rheumatol 1993; 20: 1764–8PubMed
64.
go back to reference Lafforgue P, Monjanel-Mouterde S, Durand A, et al. Is there an interaction between low doses of corticosteroids and methotrexate in patients with rheumatoid arthritis? A pharmacokinetic study in 33 patients. J Rheumatol 1993; 20: 263–7PubMed Lafforgue P, Monjanel-Mouterde S, Durand A, et al. Is there an interaction between low doses of corticosteroids and methotrexate in patients with rheumatoid arthritis? A pharmacokinetic study in 33 patients. J Rheumatol 1993; 20: 263–7PubMed
65.
go back to reference O’Dell JR. Combinations of conventional disease-modifying antirheumatic drugs. Rheum Dis Clin North Am 2001; 27: 415–26PubMedCrossRef O’Dell JR. Combinations of conventional disease-modifying antirheumatic drugs. Rheum Dis Clin North Am 2001; 27: 415–26PubMedCrossRef
66.
go back to reference Weinblatt ME, Kremer JM, Bankhurst AD, et al. A trial of etanercept, a recombinant tumor necrosis factor receptor: Fc fusion protein, in patients with rheumatoid arthritis receiving methotrexate. N Engl J Med 1999; 340: 253–9PubMedCrossRef Weinblatt ME, Kremer JM, Bankhurst AD, et al. A trial of etanercept, a recombinant tumor necrosis factor receptor: Fc fusion protein, in patients with rheumatoid arthritis receiving methotrexate. N Engl J Med 1999; 340: 253–9PubMedCrossRef
67.
go back to reference Schmeling H, Mathony K, John V, et al. A combination of etanercept and methotrexate for the treatment of refractory juvenile idiopathic arthritis: a pilot study. Ann Rheum Dis 2001; 60: 410–2PubMedCrossRef Schmeling H, Mathony K, John V, et al. A combination of etanercept and methotrexate for the treatment of refractory juvenile idiopathic arthritis: a pilot study. Ann Rheum Dis 2001; 60: 410–2PubMedCrossRef
68.
go back to reference Gerloni V, Pontikaki I, Gattinara M, et al. Efficacy of repeated intravenous infusions of an anti-tumor necrosis factor α monoclonal antibody, infliximab, in persistently active, refractory juvenile idiopathic arthritis: results of an open-labeled prospective study. Arthritis Rheum 2005 Feb; 52(2): 548–53PubMedCrossRef Gerloni V, Pontikaki I, Gattinara M, et al. Efficacy of repeated intravenous infusions of an anti-tumor necrosis factor α monoclonal antibody, infliximab, in persistently active, refractory juvenile idiopathic arthritis: results of an open-labeled prospective study. Arthritis Rheum 2005 Feb; 52(2): 548–53PubMedCrossRef
69.
go back to reference 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 Jun 1; 99: 3909–15PubMedCrossRef 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 Jun 1; 99: 3909–15PubMedCrossRef
70.
go back to reference Ortiz-Alavarez O, Morishita K, Avery G, et al. Guidelines for blood test monitoring of methotrexate toxicity in juvenile idiopathic arthritis. J Rheumatol 2004; 31: 2501–6 Ortiz-Alavarez O, Morishita K, Avery G, et al. Guidelines for blood test monitoring of methotrexate toxicity in juvenile idiopathic arthritis. J Rheumatol 2004; 31: 2501–6
71.
go back to reference Franke J, Hafner R, Lohrs U, et al. Methotrexate and liver fibrosis in juvenile chronic arthritis retrospective study of 73 liver biopsies. Monatschr Kinderheilkd 1996; 144: 147–51 Franke J, Hafner R, Lohrs U, et al. Methotrexate and liver fibrosis in juvenile chronic arthritis retrospective study of 73 liver biopsies. Monatschr Kinderheilkd 1996; 144: 147–51
72.
go back to reference Hashkes PJ, Balistreri WF, Bove KE, et al. The long-term effect of methotrexate therapy on the liver in patients with juvenile rheumatoid arthritis. Arthritis Rheum 1997; 40: 2226–34PubMedCrossRef Hashkes PJ, Balistreri WF, Bove KE, et al. The long-term effect of methotrexate therapy on the liver in patients with juvenile rheumatoid arthritis. Arthritis Rheum 1997; 40: 2226–34PubMedCrossRef
73.
go back to reference Erickson AR, Reddy V, Vogelgesang SA, et al. Usefulness of the American College of Rheumatology recommendations for liver biopsy in methotrexate-treated rheumatoid arthritis patients. Arthritis Rheum 1995; 38: 1115–9PubMedCrossRef Erickson AR, Reddy V, Vogelgesang SA, et al. Usefulness of the American College of Rheumatology recommendations for liver biopsy in methotrexate-treated rheumatoid arthritis patients. Arthritis Rheum 1995; 38: 1115–9PubMedCrossRef
74.
go back to reference Kremer JM, Alarcon GS, Lightfoot Jr RW, et al. Methotrexate for rheumatoid arthritis: suggested guidelines for monitoring liver toxicity. American College of Rheumatology. Arthritis Rheum 1994; 37: 316–28PubMedCrossRef Kremer JM, Alarcon GS, Lightfoot Jr RW, et al. Methotrexate for rheumatoid arthritis: suggested guidelines for monitoring liver toxicity. American College of Rheumatology. Arthritis Rheum 1994; 37: 316–28PubMedCrossRef
75.
go back to reference 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: 1829–37PubMedCrossRef 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: 1829–37PubMedCrossRef
76.
go back to reference Salaffi F, Manganelli P, Carotti M, et al. Methotrexate-induced pneumonitis in patients with rheumatoid arthritis and psoriatic arthritis: report of five cases and review of the literature. Clin Rheumatol 1997; 16: 296–304PubMedCrossRef Salaffi F, Manganelli P, Carotti M, et al. Methotrexate-induced pneumonitis in patients with rheumatoid arthritis and psoriatic arthritis: report of five cases and review of the literature. Clin Rheumatol 1997; 16: 296–304PubMedCrossRef
77.
go back to reference Cron RQ, Sherry DD, Wallace CA. Methotrexate-induced hypersensitivity pneumonitis in a child with juvenile rheumatoid arthritis. J Pediatr 1998; 132: 901–2PubMedCrossRef Cron RQ, Sherry DD, Wallace CA. Methotrexate-induced hypersensitivity pneumonitis in a child with juvenile rheumatoid arthritis. J Pediatr 1998; 132: 901–2PubMedCrossRef
78.
go back to reference Camiciottoli G, Trapani S, Castellani W, et al. Effect on lung function of methotrexate and non-steroid anti-inflammatory drugs in children with juvenile rheumatoid arthritis. Rheumatol Int 1998; 18: 11–6PubMedCrossRef Camiciottoli G, Trapani S, Castellani W, et al. Effect on lung function of methotrexate and non-steroid anti-inflammatory drugs in children with juvenile rheumatoid arthritis. Rheumatol Int 1998; 18: 11–6PubMedCrossRef
79.
go back to reference Pelucchi A, Lomater C, Gerloni V, et al. 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 1994; 12: 675–9PubMed Pelucchi A, Lomater C, Gerloni V, et al. 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 1994; 12: 675–9PubMed
80.
go back to reference Schmeling H, Stephan V, Burdach S, et al. Pulmonary function in children with juvenile idiopathic arthritis and effects of methotrexate therapy. Z Rheumatol 2002; 61: 168–72PubMedCrossRef Schmeling H, Stephan V, Burdach S, et al. Pulmonary function in children with juvenile idiopathic arthritis and effects of methotrexate therapy. Z Rheumatol 2002; 61: 168–72PubMedCrossRef
81.
go back to reference Graham LD, Myones BL, Rivas-Chacon RF, et al. Morbidity associated with long-term methotrexate therapy in juvenile rheumatoid arthritis. J Pediatr 1992; 120: 468–73PubMedCrossRef Graham LD, Myones BL, Rivas-Chacon RF, et al. Morbidity associated with long-term methotrexate therapy in juvenile rheumatoid arthritis. J Pediatr 1992; 120: 468–73PubMedCrossRef
82.
go back to reference Kinder AJ, Hassell AB, Brand J, et al. The treatment of inflammatory arthritis with methotrexate in clinical practice: treatment duration and incidence of adverse drug reactions. Rheumatology 2005; 44: 61–6PubMedCrossRef Kinder AJ, Hassell AB, Brand J, et al. The treatment of inflammatory arthritis with methotrexate in clinical practice: treatment duration and incidence of adverse drug reactions. Rheumatology 2005; 44: 61–6PubMedCrossRef
83.
go back to reference Grennan DM, Gray J, Loudon J, et al. Methotrexate and early postoperative complications in patients with rheumatoid arthritis undergoing elective orthopaedic surgery. Ann Rheum Dis 2001; 60: 214–7PubMedCrossRef Grennan DM, Gray J, Loudon J, et al. Methotrexate and early postoperative complications in patients with rheumatoid arthritis undergoing elective orthopaedic surgery. Ann Rheum Dis 2001; 60: 214–7PubMedCrossRef
84.
go back to reference McKendry RJ. The remarkable spectrum of methotrexate toxicities. Rheum Dis Clin North Am 1997; 23: 939–54PubMedCrossRef McKendry RJ. The remarkable spectrum of methotrexate toxicities. Rheum Dis Clin North Am 1997; 23: 939–54PubMedCrossRef
85.
go back to reference Rackham OJ, Sills JA, Davidson JE. Immunoglobulin levels in methotrexate treated paediatric rheumatology patients. Arch Dis Child 2002; 87: 147–8PubMedCrossRef Rackham OJ, Sills JA, Davidson JE. Immunoglobulin levels in methotrexate treated paediatric rheumatology patients. Arch Dis Child 2002; 87: 147–8PubMedCrossRef
86.
go back to reference Rau R. Treatment of chronic polyarthritis with methotrexate 1994: a review. Z Rheumatol 1994; 53: 199–229PubMed Rau R. Treatment of chronic polyarthritis with methotrexate 1994: a review. Z Rheumatol 1994; 53: 199–229PubMed
87.
go back to reference Cleary AG, McDowell H, Sills JA. Polyarticular juvenile idiopathic arthritis treated with methotrexate complicated by the development of non-Hodgkin’s lymphoma. Arch Dis Child 2002; 86: 47–9PubMedCrossRef Cleary AG, McDowell H, Sills JA. Polyarticular juvenile idiopathic arthritis treated with methotrexate complicated by the development of non-Hodgkin’s lymphoma. Arch Dis Child 2002; 86: 47–9PubMedCrossRef
88.
go back to reference Krugmann J, Sailer-Hock M, Muller T, et al. Epstein-Barr virus-associated Hodgkin’s lymphoma and Legionella pneumophila infection complicating treatment of juvenile rheumatoid arthritis with methotrexate and cyclosporine A. Hum Pathol 2000; 31: 253–5PubMedCrossRef Krugmann J, Sailer-Hock M, Muller T, et al. Epstein-Barr virus-associated Hodgkin’s lymphoma and Legionella pneumophila infection complicating treatment of juvenile rheumatoid arthritis with methotrexate and cyclosporine A. Hum Pathol 2000; 31: 253–5PubMedCrossRef
89.
go back to reference Londino Jr AV, Blatt J, Knisely AS. Hodgkin’s disease in a patient with juvenile rheumatoid arthritis taking weekly low dose methotrexate. J Rheumatol 1998; 25: 1245–6PubMed Londino Jr AV, Blatt J, Knisely AS. Hodgkin’s disease in a patient with juvenile rheumatoid arthritis taking weekly low dose methotrexate. J Rheumatol 1998; 25: 1245–6PubMed
90.
go back to reference Munro R, Porter DR, Sturrock RD. Lymphadenopathy in a patient with systemic onset juvenile chronic arthritis. Ann Rheum Dis 1998; 57: 513–7PubMedCrossRef Munro R, Porter DR, Sturrock RD. Lymphadenopathy in a patient with systemic onset juvenile chronic arthritis. Ann Rheum Dis 1998; 57: 513–7PubMedCrossRef
91.
go back to reference Padeh S, Sharon N, Schiby G, et al. Hodgkin’s lymphoma in systemic onset juvenile rheumatoid arthritis after treatment with low dose methotrexate. J Rheumatol 1997; 24: 2035–7PubMed Padeh S, Sharon N, Schiby G, et al. Hodgkin’s lymphoma in systemic onset juvenile rheumatoid arthritis after treatment with low dose methotrexate. J Rheumatol 1997; 24: 2035–7PubMed
92.
go back to reference Bawle EV, Conard JV, Weiss L. Adult and two children with fetal methotrexate syndrome. Teratology 1998; 57: 51–5PubMedCrossRef Bawle EV, Conard JV, Weiss L. Adult and two children with fetal methotrexate syndrome. Teratology 1998; 57: 51–5PubMedCrossRef
93.
go back to reference Kozlowski RD, Steinbrunner JV, MacKenzie AH, et al. Outcome of first-trimester exposure to low-dose methotrexate in eight patients with rheumatic disease. Am J Med 1990; 88: 589–92PubMedCrossRef Kozlowski RD, Steinbrunner JV, MacKenzie AH, et al. Outcome of first-trimester exposure to low-dose methotrexate in eight patients with rheumatic disease. Am J Med 1990; 88: 589–92PubMedCrossRef
94.
go back to reference Buckley LM, Bullaboy CA, Leichtman L, et al. Multiple congenital anomalies associated with weekly low-dose methotrexate treatment of the mother. Arthritis Rheum 1997; 40: 971–3PubMedCrossRef Buckley LM, Bullaboy CA, Leichtman L, et al. Multiple congenital anomalies associated with weekly low-dose methotrexate treatment of the mother. Arthritis Rheum 1997; 40: 971–3PubMedCrossRef
95.
go back to reference Blackburn Jr WD, Alarcon GS. Impotence in three rheumatoid arthritis patients treated with methotrexate. Arthritis Rheum 1989; 32: 1341–2PubMedCrossRef Blackburn Jr WD, Alarcon GS. Impotence in three rheumatoid arthritis patients treated with methotrexate. Arthritis Rheum 1989; 32: 1341–2PubMedCrossRef
96.
Metadata
Title
Recommendations for the Use of Methotrexate in Juvenile Idiopathic Arthritis
Authors
Dr Tim Niehues
Petra Lankisch
Publication date
01-11-2006
Publisher
Springer International Publishing
Published in
Pediatric Drugs / Issue 6/2006
Print ISSN: 1174-5878
Electronic ISSN: 1179-2019
DOI
https://doi.org/10.2165/00148581-200608060-00003

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