Serum P-glycoprotein level: a potential biomarker of DMARD failure in patients with rheumatoid arthritis

• Published in: Inflammopharmacology Vol. 26; no. 6; pp. 1375 - 1381
• Main Authors: Perez-Guerrero, E. E., Gonzalez-Lopez, L., Muñoz-Valle, J. F., Vasquez-Jimenez, J. C., Ramirez-Villafaña, M., Sanchez-Rodriguez, E. N., Gutierrez-Ureña, S. R., Cerpa-Cruz, S., Aguilar-Chavez, E. A., Cardona-Muñoz, E. G., Vazquez-Villegas, M. L., Saldaña-Cruz, A. M., Rodriguez-Jimenez, N. A., Fajardo-Robledo, N. S., Gamez-Nava, J. I.
• Format: Journal Article
• Language: English
• Published: Cham Springer International Publishing 01.12.2018
• Subjects: Allergology; Biomedical and Life Sciences; Biomedicine; Dermatology; Gastroenterology; Immunology; Original Article; Pharmacology/Toxicology; Rheumatology; P-glycoprotein; Antirheumatic drugs; Disease Activity Score; Drug resistance; Disease-modifying; Rheumatoid arthritis
• ISSN: 0925-4692; 1568-5608
• DOI: 10.1007/s10787-018-0529-2

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.