von Ahsen, N. and Armstrong, VW and Behrens, C and von Tirpitz, C and Stallmach, A and Herfarth, Hans and Stein, J and Bias, P and Adler, G and Shipkova, M and Oellerich, M and Kruis, W and Reinshagen, M (2005) Association of inosine triphosphatase 94C > A and thiopurine S-methyltransferase deficiency with adverse events and study drop-outs under azathioprine therapy in a prospective Crohn disease study. CLINICAL CHEMISTRY, 51 (12). pp. 2282-2288. ISSN 0009-9147, 1530-8561
Full text not available from this repository. (Request a copy)Abstract
Background: Azathioprine (aza) therapy is beneficial in the treatment of inflammatory bowel disease, but 10%30% of patients cannot tolerate aza therapy because of adverse drug reactions. Thiopurine S-methyltransferase (TPMT) deficiency predisposes to myelotoxicity, but its association with other side effects is less clear. Inosine triphosphatase UTPA) mutations are other pharmacogenetic polymorphisms possibly involved in thiopurine metabolism and tolerance. 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% Cl, 1.6-19.21. 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 azarelated 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 = 0.0311 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. (c) 2005 American Association for Clinical Chemistry.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | INFLAMMATORY-BOWEL-DISEASE; ISOLATED HUMAN ERYTHROCYTES; DRUG-REACTIONS; 6-THIOGUANINE NUCLEOTIDES; INDUCED MYELOSUPPRESSION; ITPA 94C-GREATER-THAN-A; GENETIC-BASIS; IN-VIVO; 6-MERCAPTOPURINE; POLYMORPHISM; |
| Subjects: | 600 Technology > 610 Medical sciences Medicine |
| Divisions: | Medicine > Lehrstuhl für Innere Medizin I |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 04 Mar 2021 10:48 |
| Last Modified: | 04 Mar 2021 10:48 |
| URI: | https://pred.uni-regensburg.de/id/eprint/35339 |
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