Document Detail

Expression of resistance markers to methotrexate predicts clinical improvement in patients with rheumatoid arthritis.
MedLine Citation:
PMID:  15345497     Owner:  NLM     Status:  MEDLINE    
BACKGROUND: Methotrexate 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). Transport proteins may affect the therapeutic efficacy of this drug in patients with rheumatoid arthritis. OBJECTIVE: To investigate the potential benefit of the presence of RFC and the absence of functional MRP for the efficacy of methotrexate treatment. METHODS: The study involved 163 patients (116 female, 47 male; mean age 59.5 years) on methotrexate (mean weekly dose 12.2 mg). RFC was determined using reverse transcriptase polymerase chain reaction, and MRP function by flow cytometry, using a calcein acetoxymethylesther/probenecid assay. Clinical response to methotrexate was evaluated by the EULAR response criteria and the ACR 20% improvement criteria. The clinical data were obtained at the beginning of methotrexate treatment and at the time of blood sampling during ongoing therapy. Patients were divided into four groups according to the presence (+) or absence (-) of RFC and functional (f) MRP. RESULTS: fMRP+/RFC+ and fMRP-/RFC- patients more often had good EULAR response rates (60%, p = 0.014, and 53%, p = 0.035, respectively) in comparison with the fMRP-/RFC+ group (29%); fMRP+/RFC- patients had a low frequency of good disease activity responses. CONCLUSIONS: Absence of fMRP plus presence of RFC did not prove to be related to beneficial effects of methotrexate, but the lack or the presence of both fMRP and RFC led to a significantly better therapeutic outcome. Determination of these markers may predict responsiveness to methotrexate.
J Wolf; T Stranzl; M Filipits; G Pohl; R Pirker; B Leeb; J S Smolen
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2004-09-02
Journal Detail:
Title:  Annals of the rheumatic diseases     Volume:  64     ISSN:  0003-4967     ISO Abbreviation:  Ann. Rheum. Dis.     Publication Date:  2005 Apr 
Date Detail:
Created Date:  2005-03-16     Completed Date:  2005-04-25     Revised Date:  2009-11-18    
Medline Journal Info:
Nlm Unique ID:  0372355     Medline TA:  Ann Rheum Dis     Country:  England    
Other Details:
Languages:  eng     Pagination:  564-8     Citation Subset:  IM    
Second Department of Medicine, Lainz Hospital, Wolkersbergenstr 1, A-1130 Vienna, Austria.
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MeSH Terms
Antirheumatic Agents / therapeutic use*
Arthritis, Rheumatoid / blood,  drug therapy*,  genetics
Biological Markers / blood
Cross-Sectional Studies
Drug Resistance / genetics
Membrane Transport Proteins / biosynthesis*,  genetics
Methotrexate / therapeutic use*
Middle Aged
Multidrug Resistance-Associated Proteins / physiology
RNA, Messenger / genetics
Reverse Transcriptase Polymerase Chain Reaction / methods
Severity of Illness Index
Treatment Outcome
Reg. No./Substance:
0/Antirheumatic Agents; 0/Biological Markers; 0/Membrane Transport Proteins; 0/Multidrug Resistance-Associated Proteins; 0/RNA, Messenger; 0/reduced folate carrier; 59-05-2/Methotrexate

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