Published online Nov 20, 2015. doi: 10.5493/wjem.v5.i4.225
Peer-review started: September 13, 2014
First decision: September 28, 2014
Revised: March 7, 2015
Accepted: August 30, 2015
Article in press: August 31, 2015
Published online: November 20, 2015
Core tip: In patients with refractory rheumatoid arthritis (RA) and high disease activity, overexpression of P-glycoprotein (P-gp) on lymphocytes can cause resistance to anti-rheumatic drugs through efflux of intracellular drugs from these cells. Lymphocytes activated by various stimuli, including tumor necrosis factor-α in RA patients apparently acquire P-gp-mediated multidrug resistance against certain anti-rheumatic drugs, which are substrates of P-gp. The use of biological agents that reduce P-gp expression as well as P-gp antagonists can successfully reduce the efflux of drugs from lymphocytes, suggesting that they can be used to overcome drug-resistance and improve clinical outcome.