Abstract | BACKGROUND: METHODS: We analyzed data from a 6-month prospective study including 71 patients with Crohn disease undergoing first-time aza treatment with respect to aza intolerance. Patients were genotyped for common TPMT and ITPA mutations and had pretherapy TPMT activity measured. RESULTS: Early drop-out (within 2 weeks) from aza therapy was associated with ITPA 94C > A [P = 0.020; odds ratio (OR), 4.6; 95% confidence interval (95% CI), 1.2-17.4] and low TPMT activity [<10 nmol/(mL erythrocytes . h); P = 0.007; OR = 5.5; 95% CI, 1.6-19.2]. A high-risk group defined by ITPA 94C > A or TPMT <10 nmol/(mL erythrocytes . h) showed significant association with early drop-out (P = 0.001; OR = 11.3; 95% CI, 2.5-50.0) and all drop-outs (P = 0.002; OR = 4.8; 95% CI, 1.8-13.3). For only drop-outs attributable to aza-related side effects (n = 16), there was a significant association with ITPA 94C > A (P = 0.002; OR = 7.8; 95% CI, 2.1-29.1). Time-to-event analysis over the 24-week study period revealed a significant association (P = 0.031) between the time to drop-out and ITPA 94C > A mutant allele carrier status. CONCLUSIONS: Patients with ITPA 94C > A mutations or low TPMT activity constitute a pharmacogenetic high-risk group for drop-out from aza therapy. ITPA 94C>A appears to be a promising marker indicating predisposition to aza intolerance.
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Authors | Nicolas von Ahsen, Victor W Armstrong, Christoph Behrens, Christian von Tirpitz, Andreas Stallmach, Hans Herfarth, Jürgen Stein, Peter Bias, Guido Adler, Maria Shipkova, Michael Oellerich, Wolfgang Kruis, Max Reinshagen, Ekkehard Schütz |
Journal | Clinical chemistry
(Clin Chem)
Vol. 51
Issue 12
Pg. 2282-8
(Dec 2005)
ISSN: 0009-9147 [Print] England |
PMID | 16214825
(Publication Type: Clinical Trial, Journal Article, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)
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Chemical References |
- Methyltransferases
- thiopurine methyltransferase
- Pyrophosphatases
- inosine triphosphatase
- Cysteine
- Azathioprine
- Alanine
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Topics |
- Adult
- Alanine
(genetics)
- Azathioprine
(adverse effects, therapeutic use)
- Crohn Disease
(drug therapy, enzymology, genetics)
- Cysteine
(genetics)
- Female
- Humans
- Male
- Methyltransferases
(deficiency, metabolism)
- Patient Dropouts
- Prospective Studies
- Pyrophosphatases
(genetics, metabolism)
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