Peripheral Lymphocyte Multidrug Resistance Activity as a Predictive Tool of Biological Therapeutic Response in Rheumatoid Arthritis.

OBJECTIVE: Multidrug resistance (MDR) transporters may be used as biomarkers to monitor disease progression in RA and as a predictive tool to establish responsiveness to biological therapy. In this multicenter clinical trial, we aimed to assess the predictive value of MDR1, MRP1 and BCRP activity measurement for biological therapeutic response in RA before as well as 4 to 6 and 12 weeks after the initiation of biological therapy.

METHODS: Peripheral blood samples were collected from 27 bDMARD Responders and 12 Non-responders at the indicated time points as well as from 35 healthy controls. MDR activity (MAF) of MDR1, MRP1 and BCRP was measured in CD3+ and CD19+ cells using the Solvo MDQ Kit™ and cell surface staining by flow cytometry following PBMC isolation.

RESULTS: At the start of therapy, MAFC (composite MAF of MRP1 and MDR1) and MAFMDR values and at 4 to 6 weeks of treatment, MAFC, MAFMRP and MAFMDR values of CD3 cells were higher in Non-responders compared to Responders. ROC analysis revealed that RA patients with MAFC values above 21.3 in CD3 cells at the start of bDMARD therapy are likely to be Non-responders. At 4 to 6 weeks of treatment, MAFC values above 20.3, MAFMRP values above 6.0 and MAFMDR values above 13.9 in CD3 cells also predict unfavorable response.

CONCLUSION: Our results indicate that the determination of MAFC values in CD3 cells of RA patients may be of predictive value prior to the initiation of biological therapy to establish whether the patient will demonstrate sufficient therapeutic response.