Pharmacogenomics in Pediatric Rheumatology
Pharmacogenomics in Pediatric Rheumatology
Purpose of review Despite major advancements in therapeutics, variability in drug response remains a challenge in both adults and children diagnosed with rheumatic disease. The genetic contribution to interindividual variability has emerged as a promising avenue of exploration; however, challenges remain in making this knowledge relevant in the clinical realm.
Recent findings New genetic associations in patients with rheumatic disease have been reported for disease modifying antirheumatic drugs, antimetabolites and biologic drugs. However, many of these findings are in need of replication, and few have taken into account the concept of ontogeny, specific to pediatrics.
Summary In the current era in which we practice, genetic variation will undoubtedly contribute to variability in therapeutic response and may be a factor that will ultimately impact individualized care. However, preliminary studies have shown that there are many hurdles that need to be overcome as we explore pharmacogenomic associations specifically in the field of pediatric rheumatology.
The role that inheritance plays in the variability of individual drug response has become an area of increased investigation over the last decade. Factors that have fueled this movement include the Human Genome Project and rapid technological advances that allow genomic exploration even in the private sector allowing anyone with enough interest and adequate finances to sequence their entire genome. Therefore, the idea of 'personalized' or individualized medicine, wherein one can potentially utilize genetic information to precisely and rationally select therapeutic interventions, optimize patient outcomes while minimizing side effects, is a natural evolution of the expanding knowledge that we have gained over the last few decades.
Challenges, however, remain in the field of pediatric rheumatology because the etiology and pathophysiology of these rare diseases remain elusive, and there are limitations in workforce to study this population of patients. Additionally, the clinical manifestations of these diseases remain heterogeneous and validated and accepted outcome measures to assess the impact of therapeutic interventions remain in evolution, making the genotype–phenotype correlation at times quite difficult. Finally, and not a small hurdle, children have been termed 'therapeutic orphans', and left behind by pharmaceutical companies in the quest for more lucrative adult markets with fewer barriers relative to the vulnerable pediatric population with age-related changes in drug metabolism and disposition. Although legislation in the United States has been designed to improve pediatric labeling for newly developed drugs, the fact remains that the off-label use of drugs not specifically tested in children is commonplace in pediatrics.
All of these factors contribute to the complexity of studying pharmacogenomics in children. The vast majority of pharmacogenomic studies have been in adults and results extrapolated to children. However, a basic understanding of ontogeny is necessary to determine the applicability of adult pharmacogenomic data to children.
Abstract and Introduction
Abstract
Purpose of review Despite major advancements in therapeutics, variability in drug response remains a challenge in both adults and children diagnosed with rheumatic disease. The genetic contribution to interindividual variability has emerged as a promising avenue of exploration; however, challenges remain in making this knowledge relevant in the clinical realm.
Recent findings New genetic associations in patients with rheumatic disease have been reported for disease modifying antirheumatic drugs, antimetabolites and biologic drugs. However, many of these findings are in need of replication, and few have taken into account the concept of ontogeny, specific to pediatrics.
Summary In the current era in which we practice, genetic variation will undoubtedly contribute to variability in therapeutic response and may be a factor that will ultimately impact individualized care. However, preliminary studies have shown that there are many hurdles that need to be overcome as we explore pharmacogenomic associations specifically in the field of pediatric rheumatology.
Introduction
The role that inheritance plays in the variability of individual drug response has become an area of increased investigation over the last decade. Factors that have fueled this movement include the Human Genome Project and rapid technological advances that allow genomic exploration even in the private sector allowing anyone with enough interest and adequate finances to sequence their entire genome. Therefore, the idea of 'personalized' or individualized medicine, wherein one can potentially utilize genetic information to precisely and rationally select therapeutic interventions, optimize patient outcomes while minimizing side effects, is a natural evolution of the expanding knowledge that we have gained over the last few decades.
Challenges, however, remain in the field of pediatric rheumatology because the etiology and pathophysiology of these rare diseases remain elusive, and there are limitations in workforce to study this population of patients. Additionally, the clinical manifestations of these diseases remain heterogeneous and validated and accepted outcome measures to assess the impact of therapeutic interventions remain in evolution, making the genotype–phenotype correlation at times quite difficult. Finally, and not a small hurdle, children have been termed 'therapeutic orphans', and left behind by pharmaceutical companies in the quest for more lucrative adult markets with fewer barriers relative to the vulnerable pediatric population with age-related changes in drug metabolism and disposition. Although legislation in the United States has been designed to improve pediatric labeling for newly developed drugs, the fact remains that the off-label use of drugs not specifically tested in children is commonplace in pediatrics.
All of these factors contribute to the complexity of studying pharmacogenomics in children. The vast majority of pharmacogenomic studies have been in adults and results extrapolated to children. However, a basic understanding of ontogeny is necessary to determine the applicability of adult pharmacogenomic data to children.
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