Background
Methotrexate has been predominantly used for more than 20 years as first-line therapy for rheumatoid arthritis (RA) patients. Although this drug is available and effective, however some of the patients may fail to respond to it.
Objectives
To assess serum P-gp level as a risk marker of therapeutic failure in RA patients treated with methotrexate and to correlate its level with the disease activity score (DAS 28).
Subject and methods
Eighty RA patients were on methotrexate therapy at least 6 months prior to study onset. Out of the recruited patients, 25 responders to MTX with DAS 28 3.2 (Group II). Serum levels of P-glycoprotein were estimated by ELISA.
Results
Responding patients to MTX had significant lower serum P-glycoprotein compared to patients with MTX failure (p=0.041). High serum P-gp level was significantly associated with number of swollen joints (p=0.001), number of tender joints (P=0.003), deteriorated patient global health score (p=0.002), DAS 28, ESR (P = 0.01), rheumatoid factor (p < 0.001), and base line anti CCP (P = 0.002). After adjusting for confounding variables, elevated P-gp remained associated with MTX failure (Hazard Ratio 2.78, 95% CI 1.37 ─ 5.64, P =0.035).
Conclusions
Elevated serum P- gp resulted in resistance to methotrexate therapy in RA patients. High serum P-gp in association with high DAS 28 score. So, assessment of P-gp level may improve the ability to tailor treatment for each RA patient.