POS0868 THE FORMULA TO PREDICT TACROLIMUS CONCENTRATION ACCORDING TO GENOTYPING OF CYP3A5 IS USEFUL FOR EFFECTIVE TREATMENT IN INTERSTITIAL LUNG DISEASE WITH DERMATOMYOSITIS
Authors: M. Katayama, S. Horibata, S. Takahashi, M. Takahashi, T. Saito, N. Amano, K. Yoshida, S. Hatachi, K. Yorifuji, S. Kumagai
Journal: Annals of the Rheumatic Diseases (2021)

Background: Tacrolimus (TAC), an immunosuppressant, can be used in second-line maintenance therapy for interstitial lung disease (ILD) in patients with dermatomyositis (DM) [1]. Although some studies reported the clinical efficacy of initial high-trough levels of TAC in combination with GC and IVCY in induction therapy for severe DM-ILD [2], there have been no useful clinical tools for deciding suitable initial dose of TAC. Genotype of polymorphisms in cytochrome P450 (CYP) 3A5 enzyme was reported to play an important role in pharmacokinetics of TAC [3], and we made a formula for deciding initial dose of TAC according to CYP3A5 genotypes in our previous study. Objectives: In our previous study (retrospective study), we set the target trough according to the severity for nine DM-ILD patients, six of whom were CYP3A5 *3/*3 and investigated the dose of TAC that could attain the trough using their CYP3A5 genootyping. Using these results, we developed a formula for deciding initial daily dose of TAC (target trough*weight / [(151.1, if CYP3A5 *3/*3) or (86.5, if CYP3A5 *1 allele)]). In this study, we prospectively examined the usefulness and accuracy of this formula. Methods: We introduced TAC for new six DM-ILD patients who visited our hospital between November 2019 and May 2020 (prospective study). The starting dose of TAC was decided by using the formula. We assessed the association between predicted and observed trough concentration of TAC at first measurement date (from day 2 to day4), using linear regression analysis. We also assessed the days for attaining the target trough concentration between the patients using the formula (prospective group) and six patients with CYP3A5 *3/*3 (retrospective group). Results: CYP3A5 genotype of all six DM-ILD patients were *3/*3 and underwent the TAC treatment by using the formula. The predicted and observed trough concentration of first measurement date were significantly correlated in the patients (r 2= 0.897, p=0.0041) (Fig.1). Compared with our retrospective study, target trough was more quickly attained in patients of the prospective study (Fig.2). Conclusion: The formula which we made for attainment target trough concentration based on CYP3A5 genotype was useful for deciding the starting dose of TAC. We also showed that we could attain the target trough concentration at early stage of initial treatment by using the formula. References: [1]Oddis CV and Aggarwal R. Nat Rev Rheumatol 2018;14(5):279-89. [2]Suzuka T et al. Int J Rheum dis 2019;22: 303-13. [3]Y. Muraki et al. Exp Ther Med 2018;15:532-38. Figure 1. Correlation of predicted and observed tacrolimus trough concentration at first measurement in the prospective study Figure 2. Days to attain the target trough concentration of tacrolimus in the prospective group and the retrospective group Disclosure of Interests: None declared