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AB0036 Analysis of genetic polymorphisms in folate pathway affecting the efficacy of methotrexate in japanese patients with rheumatoid arthritis
  1. Y. Tazoe1,
  2. H. Hayashi1,
  3. S. Tsuboi2,
  4. M. Morishita1,
  5. T. Arai1,
  6. M. Ohshima3,
  7. T. Matsuyama3,
  8. K. Kosuge4,
  9. H. Yamada4,
  10. D. Tsuji1,
  11. K. Inoue1,
  12. K. Itoh1
  1. 1Department of Clinical Pharmacology & Genetics, School of Pharmaceutical Sciences, University of Shizuoka
  2. 2Department of Rheumatology
  3. 3Department of Pharmacy, Shizuoka Kousei Hospital
  4. 4Department of Drug Evaluation & Informatics, School of Pharmaceutical Sciences, University of Shizuoka, Shizuoka, Japan

Abstract

Background Low-dose methotrexate (MTX) is an anchor drug in the medication of rheumatoid arthritis (RA). However, MTX exhibited large inter-individual and inter-ethnic differences in the dose required for its anti-inflammatory effect. In order to maintain the low disease activity, there are also the patients who needs increase in dose of MTX, and who needs co-administration of biologic disease modifying anti-rheumatic drugs (bDMARDs). If there is a marker for predicting the effect of MTX, it will become possible to increase the dose of MTX or to prescribe bDMARDs for the patient at an early stage.

Objectives The present study examined genetic polymorphisms related to folate metabolism pathway in RA patients, with the intention of building evidence for implementing individualized drug therapy with MTX.

Methods Among Japanese patients who gave written consent under treatment at the Department of Rheumatology at Shizuoka Kousei Hospital, the present study examined a patient group with an unsatisfactory response to MTX and undergoing concomitant treatment with bDMARDs (bDMARDs concomitant group) and a patient group who had a stable response to MTX. We used DAS28 as an index for disease activity. To analyze genetic polymorphisms involved in folate metabolism pathway, we used a PCR-RFLP method and a direct sequencing method. The present study was conducted with the approval of the ethics committees of each related organization.

Results Eighty-nine patients were treated with MTX alone. MTX and bDMARDs were co-administered to 81 patients because of the insufficient efficacy of MTX (bDMARDs concomitant group). The results of a multivariate analysis using the concomitant of bDMARDs as the objective variable revealed a significant association between age and the G80A polymorphism of the reduced folate carrier 1 gene (RFC1), as an explanatory variable (p=0.0018).

Conclusions DAS28 values showed no significant difference between the bDMARDs concomitant group and the MTX group, and both groups are thought to have achieved a therapeutic effect with the same degree of stability. Compared to patients with the A allele, patients with the G allele had less intracellular MTX uptake and therefore had poor efficacy; a greater number of them were found to be bDMARDs concomitant cases. The results of the present study suggest the possibility that the RFC1 G80A polymorphism may be a useful marker for predicting MTX efficacy in Japanese patients with RA.

Disclosure of Interest None Declared

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