Bangma, A. (Amber) (2019) Pharmacogenetic profiling in Inflammatory Bowel Disease. thesis, Medicine.
Full text available on request.Abstract
Background: Inflammatory bowel disease (IBD) is a chronic intestinal inflammatory disorder. Because medical therapy for IBD is characterized by a high failures rates, better stratification of patients based on predicted treatment outcomes is necessary. Pharmacogenetic (PGx) testing entails testing for associations between genetic variation and therapeutic outcomes, and may enable better prediction of treatment outcomes for drugs used in IBD treatment. The aim of this study was to assess of the potential use of combined PGx profiling in the management of IBD. Methods: Retrospective analysis of 1097 IBD patients was done on the presence of 5-aminosalicylate (5-ASA) induced nephrotoxicity, thiopurine-induced pancreatitis (TIP), thiopurine-induced myelosuppression (TIM), and/or immunogenicity of TNF-antagonists (ITA). A computational pipeline was made to translate genetic data into a predicted risk for each adverse drug reaction per patient. We calculated clinical validity and utility estimates with a case-control study and analyzed the entire cohort to display real-world consequences of PGx testing for patients with IBD. Results: For PGx testing for TIM, we calculated a sensitivity of 35%, specificity of 92%, negative predictive value (NPV) of 95%, positive predictive value (PPV) of 25%, number needed to genotype (NNG) of 50 and number needed to harm (NNH) of 4. PGx testing for 5-ASA induced nephrotoxicity has a sensitivity of 44%, specificity of 66%, NPV of 100%, and PPV of 0.39%. A sensitivity of 62%, specificity of 56%, NPV of 97%, PPV of 5.5%, NNG of 206 and NNH of 13 was found for PGx testing for TIP. For PGx testing for ITA, we calculated a sensitivity of 47%, a specificity of 63%, a NPV of 79%, a PPV of 29%, NNG of 37 and NNH of 10. When combining PGx testing for TIP, TIM and ITA, we found an NNG of 26 and NNH of 7 to prevent one adverse drug reaction. Within our entire cohort, we found that PGx profiling could have identified 59 cases before treatment. Conclusion: We found that PGx testing for TIP, TIM and ITA as part of combined PGx profiling is clinically valid and useful. Therefore, we conclude that combined PGx profiling for TIP, TIM and ITA should be implemented into clinical guidelines for the management of IBD.
| Item Type: | Thesis (Thesis) |
|---|---|
| Supervisor name: | Supervised by: and Voskuil, Drs. M.D. and Uniken Venema, Drs. W.T.C. and Weersma, Prof. Dr. R.K. and Department of Gastroenterology and Hepatology & Department o and University of Groningen & University Medical Centre Groninge and the Netherlands and Festen, Dr. E.A.M. |
| Faculty: | Medical Sciences |
| Date Deposited: | 25 Jun 2020 10:54 |
| Last Modified: | 25 Jun 2020 10:54 |
| URI: | https://umcg.studenttheses.ub.rug.nl/id/eprint/1511 |
Actions (login required)
 |
View Item |