polymorphisms in cytochrome p450 2c19 enzyme and cessation of leflunomide in patients with rheumatoid arthritis多态性在细胞色素p450 2 c19酶和戒烟的leflunomide风湿性关节炎患者.pdf

Wiese et al. Arthritis Research Therapy 2012, 14:R163 /content/14/4/R163 RESEARCH ARTICLE Open Access Polymorphisms in cytochrome P450 2C19 enzyme and cessation of leflunomide in patients with rheumatoid arthritis 1,2*† 1,2† 1,2 3 1,2 Michael D Wiese , Matthew Schnabl , Catherine O’Doherty , Llewellyn D Spargo , Michael J Sorich , Leslie G Cleland3,4 and Susanna M Proudman3,4 Abstract Introduction: Rational selection of disease modifying anti-rheumatic drugs in the treatment of rheumatoid arthritis (RA) has many potential advantages, including rapid disease control, reduced long-term disability and reduced overall cost to the healthcare system. Inter-individual genetic differences are particularly attractive as markers to predict efficacy and toxicity, as they can be determined rapidly prior to drug selection. The aims of this study, therefore, were to investigate the association between differences in genes associated with the metabolism, clearance and efficacy of leflunomide with its cessation in a group of rheumatoid arthritis patients who were treated with an intensive contemporary, treat-to-target approach. Methods: This retrospective cohort study identified all individuals who received leflunomide and were enrolled in the Early Arthritis inception cohort at the Royal Adelaide Hospital between 2001 and July 2011. Inclusion criteria were age (18) and a diagnosis of rheumatoid arthritis. Patients were excluded if a DNA sample was not available, if they withdrew from the cohort or if clinical data were insufficient. Subjects were followed for 12 months or until either another disease modifying antirheumatic drug was added or leflunomide was ceased. The follow