E E Perez-Guerrero1, L Gonzalez-Lopez2,3, J F Muñoz-Valle1, J C Vasquez-Jimenez4, M Ramirez-Villafaña5,6, E N Sanchez-Rodriguez2, S R Gutierrez-Ureña7, S Cerpa-Cruz7, E A Aguilar-Chavez8,9, E G Cardona-Muñoz10, M L Vazquez-Villegas11,12, A M Saldaña-Cruz10, N A Rodriguez-Jimenez10, N S Fajardo-Robledo13, J I Gamez-Nava14,15. 1. Instituto de Investigación en Ciencias Biomédicas, Centro Universitario de Ciencias de la Salud (CUCS), Universidad de Guadalajara (U de G), Guadalajara, Jalisco, Mexico. 2. Programa de Doctorado en Farmacología, CUCS, U de G, Guadalajara, Jalisco, Mexico. 3. Hospital General Regional 110, Instituto Mexicano del Seguro Social (IMSS), Guadalajara, Jalisco, Mexico. 4. Centro Universitario de Investigaciones Biomédicas, Universidad de Colima, Colima, Mexico. 5. Programa de Doctorado en Ciencias Médicas, Universidad de Colima, Colima, Mexico. 6. Unidad de Investigación Biomédica 02, UMAE, Hospital de Especialidades, Centro Médico Nacional de Occidente, IMSS, Guadalajara, Jalisco, Mexico. 7. División de Reumatología, Hospital Civil de Guadalajara "Fray Antonio Alcalde", Guadalajara, Jalisco, México. 8. Unidad de Medicina Familiar 2, IMSS, Guadalajara, Jalisco, Mexico. 9. Centro Universitario de Tonalá, U de G, Tonalá, Jalisco, Mexico. 10. Departamento de Fisiología, CUCS, U de G, Jalisco, Mexico. 11. Departamento de Epidemiología, Unidad Médica Familiar 4, IMSS, Guadalajara, Jalisco, Mexico. 12. Departamento de Salud Pública, CUCS, U de G, Guadalajara, Jalisco, Mexico. 13. Laboratorio de Investigación y Desarrollo Farmacéutico, Centro Universitario de Ciencias Exactas e Ingenierías, U de G, Guadalajara, Jalisco, Mexico. 14. Programa de Doctorado en Farmacología, CUCS, U de G, Guadalajara, Jalisco, Mexico. drivangamez@prodigy.net.mx. 15. Unidad de Investigación Biomédica 02, UMAE, Hospital de Especialidades, Centro Médico Nacional de Occidente, IMSS, Guadalajara, Jalisco, Mexico. drivangamez@prodigy.net.mx.
Abstract
OBJECTIVES: To evaluate the utility of elevated serum P-glycoprotein (P-gp) as a risk marker of therapeutic response failure in rheumatoid arthritis (RA) patients treated with disease-modifying antirheumatic drugs (DMARDs). METHODS: A cross-sectional study was conducted in 151 RA patients. Patients were classified into two groups according to the response achieved in terms of the disease activity score (DAS)28 after ≥ 6 months: (1) patients with a therapeutic response to DMARDs, with DAS28 < 3.2; and (2) patients without a response to DMARDs, with persistent DAS28 ≥ 3.2. We explored a wide group of clinical factors associated with therapeutic resistance. Serum P-gp levels were measured by ELISA. The risk of P-gp elevation as a marker of failure to achieve a therapeutic response to DMARDs was computed using multivariate logistic regression. RESULTS: Serum P-gp levels were significantly higher in RA patients (n = 151) than in the controls (n = 30) (158.70 ± 182.71 ng/mL vs. 14.12 ± 8.97 ng/mL, p < 0.001). The P-gp level was correlated with the DAS28 score (r = 0.39, p < 0.001). RA patients with DMARD failure had higher serum P-gp levels than patients with a therapeutic response (206 ± 21.47 ng/mL vs 120.60 ± 15.70 ng/mL; p = 0.001). High P-gp levels increased the risk of DMARD failure (OR 3.36, 95% CI 1.54-7.27, p = 0.001). After adjusting for confounding variables, elevated P-gp remained associated with DMARD failure (OR 2.64, 95% CI 1.29-5.40, p = 0.01). CONCLUSION: Elevated serum P-gp is associated with DMARD failure. The P-gp level can be considered a clinical tool for evaluating the risk of DMARD failure in patients; however, future prospective studies should be performed to evaluate the utility of this marker in predicting long-term responses.
OBJECTIVES: To evaluate the utility of elevated serum P-glycoprotein (P-gp) as a risk marker of therapeutic response failure in rheumatoid arthritis (RA) patients treated with disease-modifying antirheumatic drugs (DMARDs). METHODS: A cross-sectional study was conducted in 151 RApatients. Patients were classified into two groups according to the response achieved in terms of the disease activity score (DAS)28 after ≥ 6 months: (1) patients with a therapeutic response to DMARDs, with DAS28 < 3.2; and (2) patients without a response to DMARDs, with persistent DAS28 ≥ 3.2. We explored a wide group of clinical factors associated with therapeutic resistance. Serum P-gp levels were measured by ELISA. The risk of P-gp elevation as a marker of failure to achieve a therapeutic response to DMARDs was computed using multivariate logistic regression. RESULTS: Serum P-gp levels were significantly higher in RApatients (n = 151) than in the controls (n = 30) (158.70 ± 182.71 ng/mL vs. 14.12 ± 8.97 ng/mL, p < 0.001). The P-gp level was correlated with the DAS28 score (r = 0.39, p < 0.001). RApatients with DMARD failure had higher serum P-gp levels than patients with a therapeutic response (206 ± 21.47 ng/mL vs 120.60 ± 15.70 ng/mL; p = 0.001). High P-gp levels increased the risk of DMARD failure (OR 3.36, 95% CI 1.54-7.27, p = 0.001). After adjusting for confounding variables, elevated P-gp remained associated with DMARD failure (OR 2.64, 95% CI 1.29-5.40, p = 0.01). CONCLUSION: Elevated serum P-gp is associated with DMARD failure. The P-gp level can be considered a clinical tool for evaluating the risk of DMARD failure in patients; however, future prospective studies should be performed to evaluate the utility of this marker in predicting long-term responses.
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