AOX1 and XDH Enzymes Genotyping and its Effect on Clinical Response to Azathioprine in Inflammatory Bowel Disease Patients Among Jordanian Population

Background and Objective: Inflammatory bowel disease (IBD) is a set of chronic inflammatory gastrointestinal disorders, which include ulcerative colitis (UC) and Crohn’s disease (CD) that affects many patients worldwide with a peak incidence in early adult life. The immunosuppressant drug Azathioprine (AZA) represents one of the most useful drugs in the management of IBD. It is metabolized by many enzymes like AOX1, and XDH enzymes, the variation in the metabolism of AZA may contribute to inter-individual variation in response to this treatment. This study aims to find out if there is an association between certain AOX1 and XDH polymorphisms and AZA response in Jordanian IBD patients. Methods: One hundred IBD patients aged between (17-72) years and taking AZA were enrolled and genotyped for AOX13404G, XDH1936C and XDH2107C polymorphisms using DNA Sequencing (Sanger) method. Results and Conclusion: This study revealed that 16% of our patients were non-responders to AZA; they needed an alternative therapy (biological agent) or steroids along with AZA. There was no statistically significant association (p-value>0.05) between the AOX1 3404G, XDH 1936C and XDH 2107C polymorphisms and the response to AZA among Jordanian IBD patients. Finally, the study showed an association between the age of the patient and the response to AZA (p-value=0.013).

Economic Evaluation of Extending Medicare Immunosuppressive Drug Coverage for Kidney Transplant Recipients in the Current Era

BackgroundKidney transplant recipients must take immunosuppressant drugs to prevent rejection and maintain transplant function. Medicare coverage of immunosuppressant drugs for kidney transplant recipients ceases 36 months after transplantation, potentially increasing the risk of transplant failure. A contemporary economic analysis of extending Medicare coverage for the duration of transplant survival using current costs of immunosuppressant medications in the era of generic equivalents may inform immunosuppressant drug policy.MethodsA Markov model was used to determine the incremental cost and effectiveness of extending Medicare coverage for immunosuppressive drugs over the duration of transplant survival, compared with the current policy of 36-month coverage, from the perspective of the Medicare payer. The expected improvement in transplant survival by extending immunosuppressive drug coverage was estimated from a cohort of privately insured transplant recipients who receive lifelong immunosuppressant drug coverage compared with a cohort of Medicare-insured transplant recipients, using multivariable survival analysis.ResultsExtension of immunosuppression Medicare coverage for kidney transplant recipients led to lower costs of −$3077 and 0.37 additional quality-adjusted life years (QALYs) per patient. When the improvement in transplant survival associated with extending immunosuppressant coverage was reduced to 50% of that observed in privately insured patients, the strategy of extending drug coverage had an incremental cost–utility ratio of $51,694 per QALY gained. In a threshold analysis, the extension of immunosuppression coverage was cost-effective at a willingness-to-pay threshold of $100,000, $50,000, and $0 per QALY if it results in a decrease in risk of transplant failure of 5.5%, 7.8%, and 13.3%, respectively.ConclusionsExtending immunosuppressive drug coverage under Medicare from the current 36 months to the duration of transplant survival will result in better patient outcomes and cost-savings, and remains cost-effective if only a fraction of anticipated benefit is realized.

Feasibility of Immunosuppressant Drug Monitoring by a Microsampling Device

Background Therapeutic drug monitoring (TDM) for immunosuppressive (ISP) drugs is an important component of organ and tissue transplantation and chemotherapy management. Whole blood is the specimen type for the quantitative analysis of cyclosporine A, everolimus, sirolimus, and tacrolimus. Some alternatives to venous whole blood samples have the potential to reduce blood volume requirements and simplify sample collection and transport. Methods The feasibility of ISP drug (cyclosporine A, everolimus, sirolimus, and tacrolimus) monitoring via microsampling device (MitraTM, Neoteryx) was assessed by comparing venous samples collected and extracted using microsampling device to conventional extraction procedure. Analysis was performed by LC-MS/MS. Results All analytes were found to be linear across the measurement range of 22.7–937.0 ng/mL (18.9–779.1 nmol/L) for cyclosporine A, 2.3–44.2 ng/mL (2.4–46.1 nmol/L) for everolimus, 2.2–47.2 ng/mL (2.4–51.6 nmol/L) for sirolimus, and 2.2–41.3 ng/mL (2.7–51.4 nmol/L) for tacrolimus. Imprecision was evaluated at concentrations within the therapeutic range and was found to be 10.1% and 5.8% for cyclosporine A, 10.0% and 10.0% for everolimus, 15.0% and 11.9% for sirolimus, and 6.8% and 8.5% for tacrolimus. Method comparison (n = 30 for each analyte, using Deming regression) indicated slopes of 1.08, 1.02, 0.90, and 1.15 and intercepts of −12.8 ng/mL (−10.7 nmol/L), 0.8 ng/mL (0.8 nmol/L), 1.5 ng/mL (1.7 nmol/L), and −0.3 ng/mL (−0.3 nmol/L) for cyclosporine A, everolimus, sirolimus, and tacrolimus, respectively. Conclusions This feasibility study demonstrates that precision and bias of ≤15% can be achieved for microsampling-based ISP monitoring.