Pharmacogenomic in Colombian Patients With Rheumatoid Arthritis

Pharmacological Action

PHARMACOGENOMICS, POLYMORPHISM

The pharmacogenomics of the Colombian population with rheumatoid arthritis (RA), understood as the individual response to drugs depending on the genome of each patient, can be an explanation for the problems of effectiveness and safety that appear during the pharmacotherapeutic treatment of RA. Currently, there are limited studies on the pharmacogenomics of the Colombian population; Therefore, it is necessary to identify and classify the genetic polymorphisms characteristic of Colombian patients with RA, which influence the response of methotrexate, infliximab, etanercept, adalimumab and thus contribute to precision medicine and medical prescription according to the Specificity of the genome of each patient. This project aims to determine the association of genetic polymorphisms with the response to inhibitors of tumor necrosis factor alpha (TNFα) and methotrexate. To do this, a prospective study of cases and controls will be performed in patients in 3 hospital of Colombia with pharmacotherapeutic treatment of methotrexate, infliximab, etanercept, adalimumab, in monotherapy or combination therapy. As a result, it is expected to contribute to the performance of specific genetic tests for RA and the generation of a pharmacogenomic basis of the Colombian population with RA.

Rheumatoid arthritis is an important public health problem; In recent years better health outcomes have been achieved with the incorporation of synthetic and biological disease modifying drugs. However, problems of variability in response are reported, leading to ineffectiveness and adverse reactions in 30-40% of patients. In this sense, Pharmacogenomics, through the study of genetic variants of proteins involved in the pharmacokinetics and pharmacodynamics of drugs, becomes a way to maximize the efficacy and safety of pharmacotherapy. This work aims to give an overview of the pharmacogenomics of rheumatoid arthritis and the possibility of using genetic tools to support the pharmacotherapeutic decision in the clinical consultation, in order to improve the response to treatment of this disease. The relevance of this study is to provide the possibility of applying the candidate genes selected for their biological importance, either in the kinetics or by their relation in the pharmacological action, in the identification of individuals at risk of adverse effects or With probability of being resistant to the treatment. Therefore, it is expected that the information generated will be able to be used in daily clinical practice, contributing to identify the best therapeutic option (greater effectiveness and safety) in patients with rheumatoid arthritis. In addition, it is expected that this type of information will contribute to optimize the costs of care in this disease, which is classified in Colombia as a high cost pathology, in which medicines can reach up to 86% of the total cost. Overall, individuals respond differently to drug therapy and no medication is 100% effective in all patients, which may be due to an alteration in the pharmacokinetics and pharmacodynamics of drugs associated with conditions Genetic-environmental. In this context, the study of candidate pharmacogenomic genes has been most successful in identifying and explaining variation in pharmacological response, compared to candidate gene investigations of the disease. Therefore, this work should contribute to the choice of the best therapeutic option in patients with RA in Colombia and, thus, to strengthen the country's health sector.

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