TY - JOUR
T1 - Pharmacogenetics and Future Therapeutic Scenarios
T2 - What Affects the Prediction of Response to Treatment with Etanercept?
AU - Murdaca, Giuseppe
AU - Gulli, Rossella
AU - Spanò, Francesca
AU - Mandich, Paola
AU - Puppo, Francesco
PY - 2014
Y1 - 2014
N2 - Enabling Technology, Genomics, Proteomics Clinical Development Phases I-III Regulatory, Quality, Manufacturing There are five tumor necrosis factor alpha (TNF-α) inhibitors available for clinical use that have demonstrated efficacy as monotherapy or in combination with other anti-inflammatory or disease-modifying anti-rheumatic drugs (DMARDs) in the treatment of immune-mediated diseases. These include the anti-TNF-α monoclonal antibodies infliximab, adalimumab, golimumab, and certolizumab pegol, and the fusion protein, etanercept. The use of pharmacogenetic testing has the potential to increase drug efficiency by identifying genetic factors responsible for a lack of response to, or toxicities from, TNF-α inhibitors, and could be used to individualize therapy. Several studies have reported associations between genetic polymorphisms and the response to etanercept, but most are small and insufficiently powered to detect effect, and markers tend to be more prognostic than predictive of therapeutic response. Limitations of pharmacogenetic studies include the use of single nucleotide polymorphisms (SNPs), genes in linkage with other loci, interaction of environmental factors, and cohort heterogeneity, all of which can complicate the relationship between genetic polymorphisms and treatment response. Further studies are needed for pharmacogenetics to become a routine part of daily clinical therapeutic practice.
AB - Enabling Technology, Genomics, Proteomics Clinical Development Phases I-III Regulatory, Quality, Manufacturing There are five tumor necrosis factor alpha (TNF-α) inhibitors available for clinical use that have demonstrated efficacy as monotherapy or in combination with other anti-inflammatory or disease-modifying anti-rheumatic drugs (DMARDs) in the treatment of immune-mediated diseases. These include the anti-TNF-α monoclonal antibodies infliximab, adalimumab, golimumab, and certolizumab pegol, and the fusion protein, etanercept. The use of pharmacogenetic testing has the potential to increase drug efficiency by identifying genetic factors responsible for a lack of response to, or toxicities from, TNF-α inhibitors, and could be used to individualize therapy. Several studies have reported associations between genetic polymorphisms and the response to etanercept, but most are small and insufficiently powered to detect effect, and markers tend to be more prognostic than predictive of therapeutic response. Limitations of pharmacogenetic studies include the use of single nucleotide polymorphisms (SNPs), genes in linkage with other loci, interaction of environmental factors, and cohort heterogeneity, all of which can complicate the relationship between genetic polymorphisms and treatment response. Further studies are needed for pharmacogenetics to become a routine part of daily clinical therapeutic practice.
KW - etanercept
KW - lymphotoxin-α
KW - TNF-α gene polymorphisms
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U2 - 10.1002/ddr.21185
DO - 10.1002/ddr.21185
M3 - Article
C2 - 25381983
AN - SCOPUS:84910033378
VL - 75
SP - S7-S10
JO - Drug Development Research
JF - Drug Development Research
SN - 0272-4391
ER -