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.
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Funding
This project was financed by a grant from the Mexican Institute for Social Security (IMSS), Fondo de Investigación en Salud (FIS), Grant no. FIS/IMSS/PROT/G14/1296.
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Comité Local de Investigación y Ética en Salud 1301. Hospital de Especialidades, Centro Médico Nacional de Occidente LIC. IGNACIO GARCIA TELLEZ, Jalisco. Date when the study was approved: April 11th, 2014. Reference Number of approval: R-2014-1301-77.
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Perez-Guerrero, E.E., Gonzalez-Lopez, L., Muñoz-Valle, J.F. et al. Serum P-glycoprotein level: a potential biomarker of DMARD failure in patients with rheumatoid arthritis. Inflammopharmacol 26, 1375–1381 (2018). https://doi.org/10.1007/s10787-018-0529-2
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DOI: https://doi.org/10.1007/s10787-018-0529-2