[Pharmacogenetics and pharmacogenomics of methotrexate. Current status and novel aspects].
Since its introduction as a disease-modifying drug, methotrexate (MTX), a folate antagonist, is regarded as a major pillar of anti-rheumatic pharmacotherapy. This has not been changed in the current era of biologicals based on recombinant proteins. Despite most promising therapeutic progress about half of rheumatoid arthritis patients still display insufficient response to anti-rheumatic drugs. Specifically, about one in four patients on MTX shows lack of sufficient therapeutic efficacy which may lead to drug discontinuation. In addition, adjustment of therapy may be necessary due to individual drug toxicity. In this context and in light of recent advances concerning the use of genetic analysis in clinical practice, the development of novel strategies which implement individualized pharmacotherapy has become a major issue for translational and clinical research. Accordingly, numerous studies have been performed in recent years analyzing genetic polymorphisms of cellular parameters which relate to MTX efficacy and toxicity. Data currently available demonstrate the potential and the limitations of clinical genetic polymorphism analyses.
pharmazentrum frankfurt, Klinikum der Goethe-Universität Frankfurt, Theodor-Stern-Kai 7, Frankfurt am Main, Germany. H.Muehl@em.uni-frankfurt.de
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H
Mühl
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Pfeilschifter
D018501:Antirheumatic Agents / Q000493:pharmacokinetics / Q000627:therapeutic use; D001172:Arthritis, Rheumatoid / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D005858:Germany; D006801:Humans; D008727:Methotrexate / Q000493:pharmacokinetics* / Q000627:therapeutic use*; D010597:Pharmacogenetics / Q000639:trends
D018501:Antirheumatic Agents; D008727:Methotrexate
Clin Rheumatol. 2008 Jun;27(6):787-9
18274813
Arthritis Rheum. 2001 Nov;44(11):2525-30
11710708
Ann Rheum Dis. 2010 May;69(5):931-2
20413572
Arthritis Rheum. 2006 Apr;54(4):1087-95
16572443
Arthritis Rheum. 2006 Feb;54(2):607-12
16447238
Science. 1999 Oct 15;286(5439):487-91
10521338
Pharmacogenetics. 2002 Apr;12(3):183-90
11927833
Nat Rev Drug Discov. 2008 Sep;7(9):759-70
18758473
J Rheumatol. 2008 Apr;35(4):572-9
18381794
J Invest Dermatol. 2008 Aug;128(8):1925-9
18256692
Arthritis Rheum. 2006 Sep;54(9):2830-9
16947783
Rheumatology (Oxford). 2008 Mar;47(3):249-55
18045808
Arthritis Rheum. 2007 Jun;56(6):1765-75
17530705
Curr Pharm Des. 2010;16(2):164-75
20205662
Z Rheumatol. 2009 Nov;68(9):747-56; quiz 757
19838716
Clin Exp Rheumatol. 2006 Sep-Oct;24(5):546-54
17181924
Curr Drug Metab. 2009 Jul;10(6):547-66
19702537
Semin Arthritis Rheum. 1998 Apr;27(5):277-92
9572710
Arthritis Rheum. 2004 Sep;50(9):2766-74
15457444
Curr Opin Rheumatol. 2009 May;21(3):216-23
19373092
Ann Rheum Dis. 2004 Oct;63(10):1227-31
15361376
Pharmacogenomics. 2007 Aug;8(8):1075-80
17716239
Pharmacogenomics J. 2007 Dec;7(6):404-7
17325736
J Rheumatol. 2009 Mar;36(3):539-45
19208607
Lancet. 2000 Nov 11;356(9242):1667-71
11089838
PLoS Med. 2008 Apr 15;5(4):e83
18416598
Ann Rheum Dis. 1999 Feb;58(2):79-84
10343521
Int J Mol Med. 2003 May;11(5):593-600
12684695
Arthritis Rheum. 2006 Oct;54(10):3095-103
17009228
Rheumatology (Oxford). 2008 Aug;47(8):1156-9
18539621