Background-6-Mercaptopurine (6-MP) has confirmed short and longterm efficacy in the treatment of IBD. However, the relation between its metabolism, efficacy, and side effects is not well understood. Aims-To assay 6-MP metabolites and to correlate levels with drug compliance, disease activity, and adverse effects of treatment.Patients-Heparinised blood was obtained prior to daily administration of6-MP in 25 adolescent Crohn's disease patients (14 ileocolitis, 11 colitis) receiving 1.2 (range 0.4-1.6) mglkg/day for a mean of 17 (range 4-65) months. Methods-Erythrocyte free bases 6-thioguanine (6-TG) and 6-methyl-mercaptopurine (6-MMP) were measured (pmol/ 8X 108 red blood cells) using reverse phase high performance liquid chromatography. Results-Disease activity (modified Harvey-Bradshaw index) improved significantly with 6-MP (p=0.001). Clinical remission was achieved in 72% ofpatients, who stopped taking prednisone, or were successfully weaned to a low alternate day dose (<0.4 mglkg/OD). Remission correlated weli with erythrocyte 6-TG (p<0.05), but not 6-MMP levels. Neutropenia was associated with 6-MP use (p<0.005), but did not correlate with erythrocyte 6-MP metabolite levels. One patient refractory to 6-MP had 6-TG, but no measureable 6-MMP production, suggesting deficient thiopurine methyl-transferase activity or poor compliance. 6-MP induced complications (hepatitis, pancreatitis, and marrow suppression) were generally associated with increased 6-MMP levels. Conclusions-These results suggest that high performance liquid chromatography measurement oferythrocyte 6-MP metabolites may provide a quantitative assessment of patient responsiveness and compliance to treatment. The data support an immunosuppressive role for 6-TG, and potential cytotoxicity of raised 6-MMP levels.
Background:
Azathioprine and 6‐mercaptopurine have proven efficacy in the treatment of Crohn’s disease. Immunosuppression is mediated by their intracellular metabolism into active 6‐thioguanine metabolites, and clinical responsiveness to therapy in patients with inflammatory bowel disease has been correlated with the measure of erythrocyte 6‐thioguanine levels.
Aims and methods:
To perform a dosing equivalency analysis and comparison of clinical efficacy in 82 patients with inflammatory bowel disease on long‐term (> 2 months) therapy with either branded azathioprine (Imuran) (n=26), generic azathioprine (n=38), or 6‐mercaptopurine (n=18), based on the measurement of erythrocyte 6‐thioguanine metabolite levels.
Results:
Disease remission was achieved in 51% (42 out of 82) of patients treated with either azathioprine or 6‐mercaptopurine therapy, and correlated well with high erythrocyte 6‐thioguanine levels (> 250 pmoles/8 × 108 RBCs). Patients treated with either branded azathioprine or 6‐mercaptopurine achieved significantly higher erythrocyte 6‐thioguanine levels than patients treated with generic azathioprine, thereby suggesting that branded azathioprine has improved oral bioavailability compared to generic azathioprine. These data are consistent with the putative immunosuppressive role of 6‐thioguanine metabolites in the treatment of inflammatory bowel disease, and provides a basis for developing a therapeutic index of clinical efficacy based on the measurement of erythrocyte 6‐thioguanine metabolite levels.
Conclusions:
Our results suggest that differences in bioavailability may have clinical relevance when considering the need to optimize erythrocyte 6‐thioguanine metabolite levels in patients deemed unresponsive to treatment on conventional drug dosages.
This case provides clinical and radiological evidence supporting an association between ascending cholangitis and acute intrahepatic portal vein thrombosis.
PurposeWe examined the prevalence of anemia, annual screening for anemia, and treatment of anemia with iron among children with inflammatory bowel disease (IBD).MethodsA retrospective study of U.S. pediatric patients with IBD was performed in the MarketScan commercial claims database from 2010–2014. Children (ages 1–21) with at least two inpatient or outpatient encounters for IBD who had available lab and pharmacy data were included in the cohort. Anemia was defined using World Health Organization criteria. We used logistic regression to determine differences in screening, incident anemia, and treatment based on age at first IBD encounter and sex.ResultsThe cohort (n=2,446) included 1,560 Crohn's disease (CD) and 886 ulcerative colitis (UC). Approximately, 85% of CD and 81% of UC were screened for anemia. Among those screened, 51% with CD and 43% with UC had anemia. Only 24% of anemia patients with CD and 20% with UC were tested for iron deficiency; 85% were iron deficient. Intravenous (IV) iron was used to treat 4% of CD and 4% UC patients overall and 8% of those with anemia.ConclusionAt least 80% of children with IBD were screened for anemia, although most did not receive follow-up tests for iron deficiency. The 43%–50% prevalence of anemia was consistent with prior studies. Under-treatment with IV iron points to a potential target for quality improvement.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.