5-aminosalicylate therapy is associated with higher 6-thioguanine levels in adults and children with inflammatory bowel disease in remission on 6-mercaptopurine or azathioprine
Autor: | Rie Maurer, Noah Wilson-Rich, Peter A. Banks, Anna Zholudev, Sarathchandra I Reddy, Frederick L. Makrauer, Sonia Friedman, Scott Hande, Athos Bousvaros, Robert Burakoff |
---|---|
Rok vydání: | 2006 |
Předmět: |
Adult
Male medicine.medical_specialty Adolescent Azathioprine Inflammatory bowel disease Gastroenterology Severity of Illness Index Internal medicine Severity of illness medicine Immunology and Allergy Humans Prospective cohort study Child Mesalamine Thioguanine Aged Retrospective Studies Thiopurine methyltransferase biology business.industry Mercaptopurine Anti-Inflammatory Agents Non-Steroidal Remission Induction Retrospective cohort study Middle Aged medicine.disease Inflammatory Bowel Diseases Ulcerative colitis Cross-Sectional Studies Treatment Outcome Immunology biology.protein Female business Biomarkers Immunosuppressive Agents medicine.drug Follow-Up Studies |
Zdroj: | Inflammatory bowel diseases. 12(4) |
ISSN: | 1078-0998 |
Popis: | Background Small uncontrolled trials have suggested that 5-aminosalicylate (5-ASA) medications increase 6-thioguanine nucleotide (6-TGn) levels in adults with Crohn's disease (CD) on azathioprine (AZA) or 6-mercaptopurine (6-MP), presumably through the inhibition of thiopurine methyltransferase (TPMT). We tested the theory that coadministration of 5-ASA agents with AZA/6-MP results in higher 6-TGn levels in a large cohort of children and adults with CD or ulcerative colitis (UC). Methods A retrospective cohort study identified all children and adults treated for IBD with AZA/6-MP at 2 tertiary medical centers. Patients were included if their TPMT genotype was known and 6-TGn and 6-methymercaptopurine (6-MMP) levels had been obtained after 3 months of clinical remission at a stable dose of AZA/6-MP. 6-TGn and 6-MMP levels were compared between patients taking and those not taking 5-ASA medications through the use of linear regression models to identify and adjust for potentially confounding variables. Results Of the 126 patients included, 88 were taking 5-ASA medications. Patients on 5-ASA agents had higher mean 6-TGn levels after adjustment for confounding variables (Delta6-TGn, 47.6 +/- 21.8 pmol/8 x 10 red blood cells; P = 0.03). CD and TPMT heterozygosity was independently associated with higher 6-TGn levels (P = 0.01 and P = 0.03, respectively). 5-ASA exposure was not associated with a change in 6-MMP levels. Conclusions We found that 5-ASA therapy is associated with higher 6-TGn levels in children and adults with IBD on 6-MP/AZA. TPMT inhibition may not explain this effect because 5-ASA exposure did not affect 6-MMP levels. The observed association of CD with higher 6-TGn levels is novel and needs to be verified in prospective studies. |
Databáze: | OpenAIRE |
Externí odkaz: |