RESEARCH - Expression of resistance markers to MTX predicts clinical improvement in patients with RA

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Ann Rheum Dis. 2004 Sep 2 [Epub ahead of print]

Expression of resistance markers to methotrexate predicts clinical

improvement in patients with rheumatoid arthritis.

Wolf J, Stranzl T, Filipits M, Pohl G, Pirker R, Leeb BF, Smolen JS.

2nd Dept. of Medicine, Lainz Hospital, Austria.

OBJECTIVE: MTX is transported into the cell by the reduced folate

carrier (RFC) and out of the cell by members of the multidrug resistance

protein family (MRP). To determine the potential influence of transport

proteins on the therapeutic efficacy of methotrexate (MTX) in patients

with rheumatoid arthritis (RA), potential benefit of the presence of RFC

and the absence of functional MRP was investigated. METHODS: 163

patients (116 female and 47 male; mean age 59.5 years) on MTX (mean

weekly dose 12.2 mg) were enrolled into the study. RFC was determined

using reverse transcriptase polymerase chain reaction and MRP function

by flow cytometry using a calcein acetoxymethylesther/probenecid assay.

Clinical response to MTX was evaluated by the EULAR response criteria

and the American College of Rheumatology improvement criteria. The

clinical data were obtained at the beginning of MTX therapy and at the

time of blood sampling during ongoing therapy. Patients were divided

into four groups according to the presence (+) and/or absence (-) of RFC

and functional (f) MRP. RESULTS: fMRP+ RFC+ and fMRP- RFC- patients had

significantly more frequent good EULAR response rates (60%; p= 0.014 and

53%; p=0.035, respectively) in comparison to the fMRP- RFC+ group (29%).

Also fMRP+ RFC- patients had a low frequency of good responses in

disease activity.

CONCLUSION: The absence of fMRP in conjunction with the presence of RFC

did not prove to be related to beneficial effects of MTX, while the lack

or the presence of both functional MRP and RFC led to a significantly

better therapeutic outcome. Determination of these markers may predict

responsiveness to MTX.

PMID: 15345497

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve & db=PubMed & list_uids=1\

5345497 & dopt=Abstract

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