Pharmacogenomic in Colombian Patients With Rheumatoid Arthritis

Pharmacological Action Clinical Trial

Official title:

Pharmacogenomic in Colombian Patients With Rheumatoid Arthritis

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT03352622
• Other study ID #: Pharmacogenomic
• Status: Recruiting
• Phase: N/A
• First received: November 10, 2017
• Last updated: February 19, 2018
• Start date: October 17, 2017
• Est. completion date: September 17, 2020

Study information

• Verified date: June 2017
• Source: Universidad de Antioquia
• Contact: Yolima Puentes, Pharmacist
• Phone: +574-3135742922
• Email: yolimap16[@]gmail.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

Description:

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 372
• Est. completion date: September 17, 2020
• Est. primary completion date: October 17, 2018
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Patients with rheumatoid arthritis on treatment with Methotrexate, Adalimumab, Infliximab or Etanercept (monotherapy or combination therapy)

• Over 18 years

• With DAS 28 (Disease Activity Score in 28 Joints) greater than 3.2

• With SDAI (Simple Disease Activity Index) less than 3.3

• Use of medication> 3 months

• Anti TNFa, used for the first time.

• Subscribe to informed consent

Exclusion Criteria:

• Patients who after applying the tool to identify other causes of variability; Identify other causes that variability in response (non-adherence to travel, forgetfulness, etc.).

• Previous use of anti TNFa drugs.

• Inpatient Patients

Related Conditions & MeSH terms

• Arthritis, Rheumatoid
• Pharmacological Action

Intervention

Other:
• CASES
Patients with RA with methotrexate therapy and inhibitors of tumor necrosis factor alpha (TNFa) infliximab, etanercept, adalimumab; That present problems of effectiveness.
• CONTROLS
Patients with RA with methotrexate therapy inhibitors of tumor necrosis factor alpha (TNFa) infliximab, etanercept, adalimumab; No problems of effectiveness

Locations

Country	Name	City	State
Colombia	Pablo Tobon Uribe Hospital	Medellin

Sponsors (2)

Lead Sponsor	Collaborator
Universidad de Antioquia	Hospital Pablo Tobón Uribe

Country where clinical trial is conducted

Colombia, 

References & Publications (4)

Bernzweig EP. Liability for malpractice...its role in nursing education. J Nurs Educ. 1969 Apr;8(2):33-41. — View Citation

Dupont JA. Significance of operative cultures in total hip arthroplasty. Clin Orthop Relat Res. 1986 Oct;(211):122-7. — View Citation

Muralidharan N, Antony PT, Jain VK, Mariaselvam CM, Negi VS. Multidrug resistance 1 (MDR1) 3435C>T gene polymorphism influences the clinical phenotype and methotrexate-induced adverse events in South Indian Tamil rheumatoid arthritis. Eur J Clin Pharmacol. 2015 Aug;71(8):959-65. doi: 10.1007/s00228-015-1885-0. Epub 2015 Jun 14. — View Citation

Salazar J, Moya P, Altés A, Díaz-Torné C, Casademont J, Cerdà-Gabaroi D, Corominas H, Baiget M. Polymorphisms in genes involved in the mechanism of action of methotrexate: are they associated with outcome in rheumatoid arthritis patients? Pharmacogenomics. 2014 Jun;15(8):1079-90. doi: 10.2217/pgs.14.67. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Number of exomes and genetic variants identified	The identification of polymorphisms will be carried out through the next generation sequencing technique	1 year