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Zeitschrift für Rheumatologie

Erschienen in:

01.02.2011 | Leitthema

Methotrexat-Toxizität

Mythen und Fakten

verfasst von: Prof. Dr. G. Keyßer

Erschienen in: Zeitschrift für Rheumatologie | Ausgabe 2/2011

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Zusammenfassung

Methotrexat (MTX) ist auch nach den heute strengeren Maßstäben für die Arzneimittelsicherheit ein gut verträgliches und langfristig sicheres Pharmakon zur Behandlung rheumatischer Erkrankungen.

Anfängliche Befürchtungen über schwerwiegende pulmonale oder hepatische Nebenwirkungen haben sich nicht bestätigt. Das Infektionsrisiko ist im Vergleich zu anderen Basistherapien nicht erhöht, ein karzinogenes Potenzial konnte auch bei langfristiger Anwendung nicht nachgewiesen werden. Daher wird MTX auch in Zukunft seinen Stellenwert in der Rheumatherapie behalten.

Menninger H, Herborn G, Sander O et al (1998) A 36 month comparative trial of methotrexate and gold sodium thiomalate in the treatment of early active and erosive rheumatoid arthritis. Br J Rheumatol 37:1060–1068PubMedCrossRef

Salliot C, van der Heijde D (2009) Long-term safety of methotrexate monotherapy in patients with rheumatoid arthritis: a systematic literature research. Ann Rheum Dis 68:1100–1104PubMedCrossRef

Papadopoulos NG, Alamanos Y, Papadopoulos IA et al (2002) Disease modifying antirheumatic drugs in early rheumatoid arthritis: a longterm observational study. J Rheumatol 29:261–266PubMed

Keysser M, Keysser G, Keysser C (1999) Long-term application of disease modifying antirheumatic drugs (DMARD). A single-center, observational study of 1681 patients with rheumatoid arthritis (RA). Z Rheumatol 58:267–276PubMedCrossRef

Gerards AH, Landewe RB, Prins AP et al (2003) Cyclosporin A monotherapy versus cyclosporin A and methotrexate combination therapy in patients with early rheumatoid arthritis: a double blind randomised placebo controlled trial. Ann Rheum Dis 62:291–296PubMedCrossRef

Choy EH, Smith C, Dore CJ, Scott DL (2005) A meta-analysis of the efficacy and toxicity of combining disease-modifying anti-rheumatic drugs in rheumatoid arthritis based on patient withdrawal. Rheumatology (Oxford) 44:1414–1421

Elkayam O, Yaron M, Zhukovsky G et al (1997) Toxicity profile of dual methotrexate combinations with gold, hydroxychloroquine, sulphasalazine and minocycline in rheumatoid arthritis patients. Rheumatol Int 17:49–53PubMedCrossRef

Rau R, Schleusser B, Herborn G, Karger T (1998) Longterm combination therapy of refractory and destructive rheumatoid arthritis with methotrexate (MTX) and intramuscular gold or other disease modifying antirheumatic drugs compared to MTX monotherapy. J Rheumatol 25:1485–1492PubMed

Amital H, Arnson Y, Chodick G, Shalev V (2009) Hepatotoxicity rates do not differ in patients with rheumatoid arthritis and psoriasis treated with methotrexate. Rheumatology (Oxford) 48:1107–1110

10.

Bernatsky S, Ehrmann FD (2008) Discontinuation of methotrexate therapy in older patients with newly diagnosed rheumatoid arthritis: analysis of administrative health databases in Quebec, Canada. Drugs Aging 25:879–884PubMedCrossRef

11.

Kent PD, Luthra HS, Michet C Jr (2004) Risk factors for methotrexate-induced abnormal laboratory monitoring results in patients with rheumatoid arthritis. J Rheumatol 31:1727–1731PubMed

12.

Bohanec GP, Logar D, Lestan B, Dolzan V (2008) Genetic determinants of methotrexate toxicity in rheumatoid arthritis patients: a study of polymorphisms affecting methotrexate transport and folate metabolism. Eur J Clin Pharmacol 64:1057–1068CrossRef

13.

Ranganathan P, Culverhouse R, Marsh S et al (2008) Methotrexate (MTX) pathway gene polymorphisms and their effects on MTX toxicity in Caucasian and African American patients with rheumatoid arthritis. J Rheumatol 35:572–579PubMed

14.

Aggarwal P, Naik S, Mishra KP et al (2006) Correlation between methotrexate efficacy & toxicity with C677T polymorphism of the methylenetetrahydrofolate gene in rheumatoid arthritis patients on folate supplementation. Indian J Med Res 124:521–526PubMed

15.

Tukova J, Chladek J, Hroch M et al (2010) 677TT genotype is associated with elevated risk of methotrexate (MTX) toxicity in juvenile idiopathic arthritis: treatment outcome, erythrocyte concentrations of MTX and folates, and MTHFR polymorphisms. J Rheumatol 37:2180–2186PubMedCrossRef

16.

Chandran V, Siannis F, Rahman P et al (2010) Folate pathway enzyme gene polymorphisms and the efficacy and toxicity of methotrexate in psoriatic arthritis. J Rheumatol 37:1508–1512PubMedCrossRef

17.

Lee YH, Song GG (2010) Associations between the C677T and A1298C polymorphisms of MTHFR and the efficacy and toxicity of methotrexate in rheumatoid arthritis: a meta-analysis. Clin Drug Investig 30:101–108PubMedCrossRef

18.

Fisher MC, Cronstein BN (2009) Metaanalysis of methylenetetrahydrofolate reductase (MTHFR) polymorphisms affecting methotrexate toxicity. J Rheumatol 36:539–545PubMedCrossRef

19.

Dervieux T, Greenstein N, Kremer J (2006) Pharmacogenomic and metabolic biomarkers in the folate pathway and their association with methotrexate effects during dosage escalation in rheumatoid arthritis. Arthritis Rheum 54:3095–3103PubMedCrossRef

20.

Wessels JA, Kooloos WM, De JR et al (2006) Relationship between genetic variants in the adenosine pathway and outcome of methotrexate treatment in patients with recent-onset rheumatoid arthritis. Arthritis Rheum 54:2830–2839PubMedCrossRef

21.

Hider SL, Thomson W, Mack LF et al (2008) Polymorphisms within the adenosine receptor 2a gene are associated with adverse events in RA patients treated with MTX. Rheumatology (Oxford) 47:1156–1159

22.

Kooloos WM, Wessels JA, ST van der et al (2010) Functional polymorphisms and methotrexate treatment outcome in recent-onset rheumatoid arthritis. Pharmacogenomics 11:163–175PubMedCrossRef

23.

Rau R (2007) Nebenwirkungen. In: Rau R (Hrsg) Das Methotrexat-Buch – Aktuelle Therapiekonzepte in der Rheumatologie und Dermatologie, 1. Aufl. Uni-Med, Bremen, S 55–63

24.

Ortiz Z, Shea B, Suarez-Almazor ME et al (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 25:36–43PubMed

25.

Visser K, van der Heijde D (2009) Optimal dosage and route of administration of methotrexate in rheumatoid arthritis: a systematic review of the literature. Ann Rheum Dis 68:1094–1099PubMedCrossRef

26.

Braun J, Kastner P, Flaxenberg P et al (2008) Comparison of the clinical efficacy and safety of subcutaneous versus oral administration of methotrexate in patients with active rheumatoid arthritis: results of a six-month, multicenter, randomized, double-blind, controlled, phase IV trial. Arthritis Rheum 58:73–81PubMedCrossRef

27.

Tilling L, Townsend S, David J (2006) Methotrexate and hepatic toxicity in rheumatoid arthritis and psoriatic arthritis. Clin Drug Investig 26:55–62PubMedCrossRef

28.

Hopwood D, Nyfors A (1977) Liver ultrastructure in psoriatics related to methotrexate therapy. 2. Findings in bile ducts from 11 methotrexate treated psoriatics and 2 controls. Acta Pathol Microbiol Scand A 85:801–811PubMed

29.

Kocharla L, Taylor J, Weiler T et al (2009) Monitoring methotrexate toxicity in juvenile idiopathic arthritis. J Rheumatol 36:2813–2818PubMedCrossRef

30.

Verstappen SM, Bakker MF, Heurkens AH et al (2010) Adverse events and factors associated with toxicity in patients with early rheumatoid arthritis treated with methotrexate tight control therapy: the CAMERA study. Ann Rheum Dis 69:1044–1048PubMedCrossRef

31.

Berends MA, Snoek J, Jong EM de et al (2006) Liver injury in long-term methotrexate treatment in psoriasis is relatively infrequent. Aliment Pharmacol Ther 24:805–811PubMedCrossRef

32.

Walker AM, Funch D, Dreyer NA et al (1993) Determinants of serious liver disease among patients receiving low-dose methotrexate for rheumatoid arthritis. Arthritis Rheum 36:329–335PubMedCrossRef

33.

Hoekstra M, Ede AE van, Haagsma CJ et al (2003) Factors associated with toxicity, final dose, and efficacy of methotrexate in patients with rheumatoid arthritis. Ann Rheum Dis 62:423–426PubMedCrossRef

34.

Kremer JM, Alarcon GS, Weinblatt ME et al (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 40:1829–1837PubMedCrossRef

35.

Lateef O, Shakoor N, Balk RA (2005) Methotrexate pulmonary toxicity. Expert Opin Drug Saf 4:723–730PubMedCrossRef

36.

Belzunegui J, Intxausti JJ, De D Jr et al (2001) Absence of pulmonary fibrosis in patients with psoriatic arthritis treated with weekly low-dose methotrexate. Clin Exp Rheumatol 19:727–730PubMed

37.

Dawson JK, Graham DR, Desmond J et al (2002) Investigation of the chronic pulmonary effects of low-dose oral methotrexate in patients with rheumatoid arthritis: a prospective study incorporating HRCT scanning and pulmonary function tests. Rheumatology (Oxford) 41:262–267

38.

Karie S, Gandjbakhch F, Janus N et al (2008) Kidney disease in RA patients: prevalence and implication on RA-related drugs management: the MATRIX study. Rheumatology (Oxford) 47:350–354

39.

White DH, Chapman PT, O’Donnell JL et al (2010) Lack of association between elevated mean red cell volume and haematological toxicity in patients receiving long-term methotrexate for rheumatoid arthritis. Intern Med J 40:561–565PubMedCrossRef

40.

Yazici Y, Sokka T, Kautiainen H et al (2005) Long term safety of methotrexate in routine clinical care: discontinuation is unusual and rarely the result of laboratory abnormalities. Ann Rheum Dis 64:207–211PubMedCrossRef

41.

Lim AY, Gaffney K, Scott DG (2005) Methotrexate-induced pancytopenia: serious and under-reported? Our experience of 25 cases in 5 years. Rheumatology (Oxford) 44:1051–1055

42.

Hornung N, Ellingsen T, Stengaard-Pedersen K, Poulsen JH (2004) Folate, homocysteine, and cobalamin status in patients with rheumatoid arthritis treated with methotrexate, and the effect of low dose folic acid supplement. J Rheumatol 31:2374–2381PubMed

43.

Kalantzis A, Marshman Z, Falconer DT et al (2005) Oral effects of low-dose methotrexate treatment. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 100:52–62PubMedCrossRef

44.

Kerstens PJ, Boerbooms AM, Jeurissen ME et al (1992) Accelerated nodulosis during low dose methotrexate therapy for rheumatoid arthritis. An analysis of ten cases. J Rheumatol 19:867–871PubMed

45.

Segal R, Caspi D, Tishler M et al (1988) Accelerated nodulosis and vasculitis during methotrexate therapy for rheumatoid arthritis. Arthritis Rheum 31:1182–1185PubMedCrossRef

46.

Veen MJ van der, HA van der, Kruize AA, Bijlsma JW (1994) Infection rate and use of antibiotics in patients with rheumatoid arthritis treated with methotrexate. Ann Rheum Dis 53:224–228PubMedCrossRef

47.

Pieringer H, Stuby U, Biesenbach G (2008) The place of methotrexate perioperatively in elective orthopedic surgeries in patients with rheumatoid arthritis. Clin Rheumatol 27:1217–1220PubMedCrossRef

48.

Kapetanovic MC, Saxne T, Sjoholm A et al (2006) Influence of methotrexate, TNF blockers and prednisolone on antibody responses to pneumococcal polysaccharide vaccine in patients with rheumatoid arthritis. Rheumatology (Oxford) 45:106–111

49.

Roon EN van, Bemt PM van den, Jansen TL et al (2009) An evidence-based assessment of the clinical significance of drug-drug interactions between disease-modifying antirheumatic drugs and non-antirheumatic drugs according to rheumatologists and pharmacists. Clin Ther 31:1737–1746PubMedCrossRef

50.

Bourre-Tessier J, Haraoui B (2010) Methotrexate drug interactions in the treatment of rheumatoid arthritis: a systematic review. J Rheumatol 37:1416–1421PubMedCrossRef

51.

Symmons DP, Silman AJ (2004) Anti-tumor necrosis factor alpha therapy and the risk of lymphoma in rheumatoid arthritis: no clear answer. Arthritis Rheum 50:1703–1706PubMedCrossRef

52.

Baecklund E, Iliadou A, Askling J et al (2006) Association of chronic inflammation, not its treatment, with increased lymphoma risk in rheumatoid arthritis. Arthritis Rheum 54:692–701PubMedCrossRef

Titel: Methotrexat-Toxizität
Mythen und Fakten
verfasst von: Prof. Dr. G. Keyßer
Publikationsdatum: 01.02.2011
Verlag: Springer-Verlag
Erschienen in: Zeitschrift für Rheumatologie / Ausgabe 2/2011
Print ISSN: 0340-1855
Elektronische ISSN: 1435-1250
DOI: https://doi.org/10.1007/s00393-010-0687-0

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