Relationship of serum P_glycoprotein to failure of methotrexate therapy in Egyptian rheumatoid arthritis patients

Background Methotrexate has been predominantly used for more than 20 years as first-line therapy for improving the clinical course and quality of life in rheumatoid arthritis (RA) patients. Although this drug is available and effective, however some of the patients may fail to respond to it, making a special challenge to Rheumatologists. Objectives This work aimed to assess the use of elevated serum P-gp 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 recruited from Outpatient Rheumatology Clinic at Mansoura University Hospital. All patients were on methotrexate therapy at a stable dosage at least 6 months prior to study onset. Disease activity was evaluated using DAS 28-ESR score. Out of the recruited patients, 25 responders to MTX with DAS 28 <3.2 (Group I) and 25 non-responders with DAS 28 > 3.2 (Group II), who met the inclusion criteria were admitted to the study. Serum levels of P-glycoprotein were estimated by ELISA. P-gp was compared in both groups and correlated with clinical factors, DAS 28 score and laboratory parameters. Multivariate analysis was performed using the Cox proportional hazards model to determine whether high serum P-gp has an independent prognostic value for poor response to methotrexate therapy. Results RA patients responding to MTX had significant lower serum P-glycoprotein compared to patients with MTX failure (p=0.041). Significant positive correlations were observed between serum P-gp levels and 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 anti CCP (P = 0.002). No significant correlations were found between serum P-gp levels and age, disease duration, and duration of methotrexate therapy. 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 results in resistance to methotrexate therapy in RA patients. High serum P-gp in association with high DAS 28 score can be used as a marker to assess the risk of MTX failure in RA.. So, assessment of P-gp level may facilitate clinical decision-making, allowing improving the ability to tailor treatment for each RA patient.