The role of Cytochrome P450 genetic disposition and patient reaction to therapy in a cohort controlled study in private practice-preliminary results from the MORE study

It has been postulated that pharmacogenetic testing applied in a practical setting could lead to significant cost savings in the health care sector while improving overall patient care and therapeutic effectiveness. The MORE study – Medication Optimization to Reduce Events – was initiated in late 2008 by awenydd diagnostics GmbH as a 6 to 8 month cohort, controlled pharmacogenetic study in German private practice to test the validity of this postulation in an actual medical environment. This is the first study of its kind worldwide. The MORE study recruited 471 patients from 26 private physician practices in southern Germany. All of the patients involved in this study are multi-morbid (greater than 2 medical indications) as well as multi-medicated (more than 3 prescription medications). Patients gave informed, written consent related to their participation in the study and have been pseudo-anonymised to ensure patient data security. Over a period of three months, patients were required to track their existing health condition on a daily basis, including potential medication side effects, visits to doctors, dentists or medical clinics and any new medication purchases, including self-medication (OTC) and herbal remedies. Use of patient self-reporting diaries was validated in studies in the USA and has been adapted for use in similar studies in Germany. Following the initial three month data collection period, patients were genotyped and this information was entered into a proprietary medical diagnostic system, which utilizes algorithms to evaluate the combined impact of genetics as well as drug-drug, food-drug and herb-drug interactions on individual medication therapy effectiveness. Based on the resulting diagnostic outcome, physicians in the study were provided a detail report related to potentially optimizing medication therapy and had free choice related to whether or not they wanted to alter their patient therapy based on these recommendations. All 471 patients have reached the mid-point in the MORE study. Seventy percent (70%) of the recommended alterations to existing medication therapy have been implemented by the physicians in the study. It should be noted that 15% of patients in the study received no recommendation to alter their medication treatment. Following adaption of their medication therapy, patients have been required to continue to track their individual events on a daily basis using the self-monitoring diary system for an additional three months. To date, only seven patients have withdrawn from the study and less than 25 patients have incomplete or have unusable daily recordings. The study is still ongoing but preliminary results from early closers (170 patients) have shown promising results, including a significant reduction in undesired events and improvement in overall patient well being compared with patient and physician evaluations at the beginning of the study. It should be noted that patients recruited for the MORE study by participating physicians were primarily „problem patients“ who exhibited unsatisfactory therapeutic results, adverse medication reactions and/or suspected non-compliance. Interestingly, although it would be expected in a statistically normal cohort study to find only 50% of the cohort with one or more genetic changes in metabolizing enzymes or uptake transporters, this study indicates that 90% of the cohort had at least one genetic change. For 65% of these patients, the genetic change was relevant to their medication metabolism and could have caused the adverse events they reported. The medication areas of most interest are anti-hypertensive, anti-lipid and anti-depressive medications. First analyses of the data have shown that 30% of the early closers or 51 patients received psycho-pharmaceuticals and that of these patients, 68% received recommendations to alter their medication therapy based on their genetic disposition, medication interactions or a combination of both. 63% of these patient physicians altered their medication therapy based on the study recommendations this included dose scheduling changes, dose reduction or increase, or a change of medication. For those patients where medication therapy was altered, almost 70% reported fewer undesired events in the second half than in the first half of the study, and only one patient reported more events. In conclusion, preliminary analysis of the MORE data reveals interesting and positive results related to prescription medication optimization, patient response and improved therapeutic outcome using pharmacogenetic testing in a private medical practice environment.

This study was supported by awenydd diagnostics GmbH