Peripheral Lymphocyte Multidrug Resistance Activity May Aid Biologic Therapeutic Response Prediction in RA

The determination of composite multidrug activity factor of MRP1 and MDR1 activity (MAFC) in CD3 cells of patients with rheumatoid arthritis (RA) may be predictive of sufficient therapeutic response before the initiation of biologic therapy, according to results of a multicenter clinical study published in The Journal of Rheumatology.

Researchers collected peripheral blood samples from 27 participants who responded to therapy with biologic disease-modifying antirheumatic drugs (bDMARDs), 12 nonresponders, and 35 healthy control patients. All the participants were evaluated before the initiation of biologic therapy, as well as between 4 to 6 weeks of treatment, and at 12 weeks of treatment.

The investigators sought to evaluate the predictive value of flow cytometry according to the measurement of multidrug resistance (MDR) activity for biologic therapeutic response in patients with RA. The activity of 3 clinically relevant MDR proteins (MDR1, MRP1, and BCRP) in CD3⁺ and CD19⁺ peripheral lymphocytes in patients with RA at the various times were assessed.

At the beginning of treatment, MAFC and multidrug activity factor of MDR1 values were higher among nonresponders compared with responders. Receiver operating characteristic analysis demonstrated that patients with RA who had MAFC values >21.3 in CD3 cells at the initiation of bDMARD therapy were likely to be nonresponders.

Moreover, at 4 to 6 weeks of treatment, MAFC values >20.3, multidrug activity factor of MRP1 values >6.0, and multidrug activity factor of MDR1 values >13.9 in CD3 cells are also predictive of an unfavorable response.

The investigators concluded that their receiver operating characteristic analysis showed that the evaluation of multidrug activity of peripheral blood lymphocytes conveys predictive value for response to bDMARD therapy in patients with RA at the initiation of treatment. Those individuals with multidrug activity factor values above the cutoff thresholds are expected to be nonresponders to biologic therapy.

Reference

Toldi G, Batel P, Baráth S, et al. Peripheral lymphocyte multidrug resistance activity as a predictive tool of biological therapeutic response in rheumatoid arthritis [published online February 1, 2019]. J Rheumatol. doi: 10.3899/jrheum.180793