SAT0154 EXAMINATION OF CYP3A5 GENOTYPE IS USEFUL FOR INTRODUCTION OF TACROLIMUS TREATMENT IN OUTPATIENTS WITH RHEUMATIC DISEASES

Background: Though several studies showed the efficacy of tacrolimus (TAC) in patients with rheumatoid arthritis (RA) in a dose-depending manner [1], the relationship between efficacy and concentration of TAC remained unclear. Genetic polymorphisms of cytochrome P450 (CYP) 3A5 were reported not only to play an important role in pharmacokinetics of TAC but also to have an influence on clinical outcomes in patients of rheumatic diseases. Several reports showed that the blood concentration of TAC in patients with a CYP3A5 *1 allele (EX, expressor) was lower than that of patients with a CYP3A5 *3/*3 (NEX, non-expressor) [2]. Objectives: To assess the relationship between efficacy and concentration of TAC in patients with RA, and to examine the usefulness of CYP3A5 genotype screening to detect outpatients suitable for TAC treatment. Methods: We examined the relationship between disease activity score (DAS) 28-CRP and concentration of TAC in patients with RA. TAC was taken after the evening meal and blood samples were taken 12±4h after TAC administration. Next we investigated the relationship between genotype frequencies of CYP3A5 and concentration of TAC in patients with rheumatic disease without having renal dysfunction (eGFR Results: The concentration of TAC tended to be negatively correlated with the disease activity of RA. The C/D value in the NEX group (n=16) was 124.7±62.1, which was significantly higher than that in the EX group (n=23; 67.7±29.8; P Conclusion: TAC showed efficacy in patients with RA in a concentration-dependent manner. EX patients may be impossible to achieve enough concentration of TAC even though using TAC of 3mg/day, approved dose for patients with RA in Japan, and NEX patients could make rapid attainment of enough concentrations of TAC in early stage of treatment, suggesting that we should consider induction of TAC only in NEX outpatients. Furthermore, drugs only slightly affected concentration of TAC in this study, suggesting that we can use TAC without any special attention to concomitant drugs. References: [1]Furst DE et al. Arthritis Rheum 2002;46:2020-28. [2]Y. Muraki et al. Exp Ther Med 2018;15:532-38. Acknowledgments: none Disclosure of Interests: Soshi Takahashi: None declared, Shinji Horibata: None declared, Saori Hatachi: None declared, Miho Takahashi: None declared, Motoko Katayama: None declared, Saki Mukohara: None declared, Norihiko Amano: None declared, Katsuyuki Yoshida: None declared, Kennosuke Yorifuji: None declared, Shunichi Kumagai Grant/research support from: Astellas, Chugai, Mitsubishi Tanabe Co.Ltds, Consultant of: Sysmex Co.Ltd, Speakers bureau: many companies