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Pharmacogenetics and Future Therapeutic Scenarios: What Affects the Prediction of Response to Treatment with Etanercept?
Author(s) -
Murdaca Giuseppe,
Gulli Rossella,
Spanò Francesca,
Mandich Paola,
Puppo Francesco
Publication year - 2014
Publication title -
drug development research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.582
H-Index - 60
eISSN - 1098-2299
pISSN - 0272-4391
DOI - 10.1002/ddr.21185
Subject(s) - etanercept , certolizumab pegol , pharmacogenetics , infliximab , golimumab , adalimumab , medicine , single nucleotide polymorphism , oncology , pharmacology , bioinformatics , disease , tumor necrosis factor alpha , genotype , biology , genetics , gene
Enabling Technology, Genomics, Proteomics Clinical Development Phases I‐III Regulatory, Quality, ManufacturingThere 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.