Genetic polymorphisms affect efficacy and adverse drug reactions of DMARDs in rheumatoid arthritis

摘要

Disease-modifying antirheumatic drugs (DMARDs) and biological agents are critical in preventing the severe complications of rheumatoid arthritis (RA). However, the outcome of treatment with these drugs in RA patients is quite variable and unpredictable. Drug-metabolizing enzymes (dihydrofolate reductase, cytochrome P450enzymes, N-acetyltransferases, etc.), drug transporters (ATP-binding cassette transporters), and drug targets (tumor necrosis factor-a receptors) are coded for by variant alleles. These gene polymorphisms may influence the pharmacokinetics, pharmacodynamics, and side effects of medicines. The cause for differences in efficacy and adverse drug reactions may be genetic variation in drug metabolism among individuals. Polymorphisms in drug transporter genes may change the distribution and excretion of medicines, and the sensitivity of the targets to drugs is strongly influenced by genetic variations. In this article, we review the genetic polymorphisms that affect the efficacy of DMARDs or the occurrence of adverse drug reactions associated with DMARDs in RA. (c) 2014 Wolters Kluwer Health | Lippincott Williams & Wilkins.