A mixture of fumaric acid esters (FAEs) is approved for the oral therapy of psoriasis. However, for a long time the active ingredient of this mixture was unknown. We reviewed the in vitro data available for the different FAEs present in the multi compound drug and elaborate how they may contribute to possible clinical effects. Although helpful overall, many in vitro data must be viewed critically because the concentrations used in the experiments exceed the plasma levels reached in patients. The data suggest that dimethylfumarate (DMF) is the most active compound, mediating the major therapeutic effect after metabolization into monomethylfumarate (MMF) via an according receptor expressed on target cells. Identifying the active pharmaceutical ingredient within a mixture of compounds helps to subsequently eliminate unnecessary, potentially harmful compounds. This provides a promising example for an alternative precision medicine approach in clinical practice.
{"title":"Genomics Vault: A framework for precision medicine data management","authors":"Bhupinder Bhullar, Guy Gross, Hakan Akozek","doi":"10.18063/apm.v2i2.28","DOIUrl":"https://doi.org/10.18063/apm.v2i2.28","url":null,"abstract":"A mixture of fumaric acid esters (FAEs) is approved for the oral therapy of psoriasis. However, for a long time the active ingredient of this mixture was unknown. We reviewed the in vitro data available for the different FAEs present in the multi compound drug and elaborate how they may contribute to possible clinical effects. Although helpful overall, many in vitro data must be viewed critically because the concentrations used in the experiments exceed the plasma levels reached in patients. The data suggest that dimethylfumarate (DMF) is the most active compound, mediating the major therapeutic effect after metabolization into monomethylfumarate (MMF) via an according receptor expressed on target cells. Identifying the active pharmaceutical ingredient within a mixture of compounds helps to subsequently eliminate unnecessary, potentially harmful compounds. This provides a promising example for an alternative precision medicine approach in clinical practice.","PeriodicalId":345327,"journal":{"name":"Advances in Precision Medicine","volume":"7 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2017-10-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"129829362","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2016-03-18DOI: 10.18063/APM.2016.01.007
R. Holland
The last decade has seen an extraordinary amount of effort devoted in biomedical research to the field of biomarkers. There have been some notable successes with novel markers being adopted into clinical practice bringing clear clinical benefit to some patients — particularly with the increasing numbers of medicines being approved with companion diagnostics. However, it is fair to say that there has not yet been the numbers of clinically valuable biomarkers brought to medical practice that the research effort would seem to warrant. This paper evaluates examples of successful biomarkers, markers which might be considered partial successes and a few problematic examples and argues that more effort spent in the validation phase of marker development, and less in the discovery phase might be a more efficient way to allocate research resources.
{"title":"What makes a good biomarker?","authors":"R. Holland","doi":"10.18063/APM.2016.01.007","DOIUrl":"https://doi.org/10.18063/APM.2016.01.007","url":null,"abstract":"The last decade has seen an extraordinary amount of effort devoted in biomedical research to the field of biomarkers. There have been some notable successes with novel markers being adopted into clinical practice bringing clear clinical benefit to some patients — particularly with the increasing numbers of medicines being approved with companion diagnostics. However, it is fair to say that there has not yet been the numbers of clinically valuable biomarkers brought to medical practice that the research effort would seem to warrant. This paper evaluates examples of successful biomarkers, markers which might be considered partial successes and a few problematic examples and argues that more effort spent in the validation phase of marker development, and less in the discovery phase might be a more efficient way to allocate research resources.","PeriodicalId":345327,"journal":{"name":"Advances in Precision Medicine","volume":"41 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2016-03-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"129646650","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2016-03-17DOI: 10.18063/APM.2016.01.004
Saskia Weber, M. Pietzsch, O. Bestard, J. Grinyó, O. Viklicky, P. Reinke
Immunosuppression (IS) following solid organ transplantation is indicated to avoid rejection but puts a significant burden on patients and healthcare systems due to life-long medication dependency and associated costs. Organ-tolerance with low or no IS medication has been observed, and might be forecasted with the help of appropriate biomarkers. Individualized treatments raise the question whether benefits of individualization outweigh the costs of stratification. This article outlines the importance of early economic evaluation in the context of biomarker-guided IS and discusses challenges that an economic evaluation should address, using the BIO-DrIM project as a reference example. We report on design aspects and health-economic study integration into several newly designed biomarker trials. In these studies, health-economic endpoints were defined to measure benefits of individualization and to compare them to the costs associated with stratification. Key economic outcomes to be collected are resource consumption and patient quality of life. Test accuracy of the biomarker-stratification is critical for the clinical success and the health-economic viability of an individualized reduced IS regime. However, IS regimes are not well standardized, rendering comparator choice difficult. The multi-national character of the trials adds further complexity that needs to be addressed. Developers of biomarker tests should stress the importance of integrating health-economic evaluations early into product-development.
{"title":"Investigating the health-economic profiles of biomarker-driven immunosuppresion (BIO-DrIM) following solid organ transplantation","authors":"Saskia Weber, M. Pietzsch, O. Bestard, J. Grinyó, O. Viklicky, P. Reinke","doi":"10.18063/APM.2016.01.004","DOIUrl":"https://doi.org/10.18063/APM.2016.01.004","url":null,"abstract":"Immunosuppression (IS) following solid organ transplantation is indicated to avoid rejection but puts a significant burden on patients and healthcare systems due to life-long medication dependency and associated costs. Organ-tolerance with low or no IS medication has been observed, and might be forecasted with the help of appropriate biomarkers. Individualized treatments raise the question whether benefits of individualization outweigh the costs of stratification. This article outlines the importance of early economic evaluation in the context of biomarker-guided IS and discusses challenges that an economic evaluation should address, using the BIO-DrIM project as a reference example. We report on design aspects and health-economic study integration into several newly designed biomarker trials. In these studies, health-economic endpoints were defined to measure benefits of individualization and to compare them to the costs associated with stratification. Key economic outcomes to be collected are resource consumption and patient quality of life. Test accuracy of the biomarker-stratification is critical for the clinical success and the health-economic viability of an individualized reduced IS regime. However, IS regimes are not well standardized, rendering comparator choice difficult. The multi-national character of the trials adds further complexity that needs to be addressed. Developers of biomarker tests should stress the importance of integrating health-economic evaluations early into product-development.","PeriodicalId":345327,"journal":{"name":"Advances in Precision Medicine","volume":"17 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2016-03-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"125213122","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2016-03-17DOI: 10.18063/APM.2016.01.001
H. Volk, B. Banas, F. Bemelman, O. Bestard, Sophie Brouard5, C. Cuturi, Josep M Grinyó, M. Hernandez-Fuentes, M. Koch, B. Nashan, I. Rebollo-Mesa, A. Sánchez‐Fueyo, B. Sawitzki, Ineke J M ten Berge, O. Viklicky, Kathryn Wood K, P. Reinke
Solid organ transplantation has emerged as the “gold standard” therapy for end-stage organ failure as it improves both quality of life and survival. Despite the progress in short-term graft survival, that is closely associated with the impressive reduction of acute rejections within the first year, long-term graft and patient survival remain almost unchanged and unsatisfactory. Incomplete control of chronic allograft injury but particularly the adverse effects of long-term immunosuppression, such as graft toxicity, diabetes, cardiovascular events, infections, and tumours continue to challenge the long-term success. In general, immunosuppression is applied as one-size-fits-all strategy. This can result in over- and under-immunosuppression of patients with low and high allo-responsiveness, respectively. Trial- and -error strategies to minimize or even completely wean of immunosuppression have a high failure rate. Consequently, there is an unmet medical need to develop biomarkers allowing objective risk stratification of transplant patients. To achieve this goal, we engaged in an academic-industrial partnership. The central focus of the European-wide BIO-DrIM consortium (BIOmarker-Driven IMmmunosuppression) is the implementation of biomarker-guided strategies for personalizing immunosuppress- ion to improve the long-term outcome and to decrease the adverse effects and costs of chronic immunosuppression in solid organ transplant patients. The concept includes four innovative investigator-driven clinical trials designed by the consortium.
{"title":"Strategy to achieve biomarker-driven immunosuppression after solid organ transplantation by an academic-industry partnership within the European BIO-DrIM consortium","authors":"H. Volk, B. Banas, F. Bemelman, O. Bestard, Sophie Brouard5, C. Cuturi, Josep M Grinyó, M. Hernandez-Fuentes, M. Koch, B. Nashan, I. Rebollo-Mesa, A. Sánchez‐Fueyo, B. Sawitzki, Ineke J M ten Berge, O. Viklicky, Kathryn Wood K, P. Reinke","doi":"10.18063/APM.2016.01.001","DOIUrl":"https://doi.org/10.18063/APM.2016.01.001","url":null,"abstract":"Solid organ transplantation has emerged as the “gold standard” therapy for end-stage organ failure as it improves both quality of life and survival. Despite the progress in short-term graft survival, that is closely associated with the impressive reduction of acute rejections within the first year, long-term graft and patient survival remain almost unchanged and unsatisfactory. Incomplete control of chronic allograft injury but particularly the adverse effects of long-term immunosuppression, such as graft toxicity, diabetes, cardiovascular events, infections, and tumours continue to challenge the long-term success. In general, immunosuppression is applied as one-size-fits-all strategy. This can result in over- and under-immunosuppression of patients with low and high allo-responsiveness, respectively. Trial- and -error strategies to minimize or even completely wean of immunosuppression have a high failure rate. Consequently, there is an unmet medical need to develop biomarkers allowing objective risk stratification of transplant patients. To achieve this goal, we engaged in an academic-industrial partnership. The central focus of the European-wide BIO-DrIM consortium (BIOmarker-Driven IMmmunosuppression) is the implementation of biomarker-guided strategies for personalizing immunosuppress- ion to improve the long-term outcome and to decrease the adverse effects and costs of chronic immunosuppression in solid organ transplant patients. The concept includes four innovative investigator-driven clinical trials designed by the consortium.","PeriodicalId":345327,"journal":{"name":"Advances in Precision Medicine","volume":"1 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2016-03-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"128912863","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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