REVIEW - Drug insight: resistance to MTX and other DMARDs - from bench to bedside

[Guest guest]

Nat Clin Pract Rheumatol. 2007 Jan;3(1):26-34.

Drug Insight: resistance to methotrexate and other disease-modifying

antirheumatic drugs-from bench to bedside.

JW van der Heijden is a trainee in the MD/PhD program, BAC Dijkmans is a

Full Professor in Rheumatology, and G Jansen is Head of the Experimental

Rheumatology section in the Department of Rheumatology, and RJ Scheper holds

a Chair in Experimental Pathology in the Department of Pathology, all at the

VU University Medical Center, Amsterdam, The Netherlands.

The chronic nature of rheumatoid arthritis (RA) means that patients require

drug therapy for many years. Many RA patients, however, have to discontinue

treatment because of drug-related toxic effects, loss of efficacy, or both.

The underlying molecular cause for loss of efficacy of antirheumatic drugs

is not fully understood, but it might be mediated, at least in part, by

mechanisms shared with resistance to anticancer drugs. This Review outlines

molecular mechanisms that could be involved in the onset of resistance to,

or the loss of efficacy of, disease-modifying antirheumatic drugs in RA

patients, including methotrexate, sulfasalazine, chloroquine,

hydroxychloroquine, azathioprine, and leflunomide. The mechanisms suggested

are based on findings from experimental laboratory studies of specific

drug-uptake and drug-efflux transporters belonging to the superfamily of

multidrug-resistance transporters, alterations in intracellular drug

metabolism, and genetic polymorphisms of drug transporters and metabolic

enzymes. We also discuss strategies to overcome resistance and the current

clinical studies aiming to predict response and risk of toxic effects. More

in-depth knowledge of the mechanisms behind these features could help

facilitate a more efficient use of disease-modifying antirheumatic drugs.

PMID: 17203006

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed & cmd=Retrieve & dopt=Abstra\

ctPlus & list_uids=17203006

Not an MD