TY - JOUR T1 - Pharmacogenetic and metabolite measurements are associated with clinical status in patients with rheumatoid arthritis treated with methotrexate: results of a multicentred cross sectional observational study JF - Annals of the Rheumatic Diseases JO - Ann Rheum Dis SP - 1180 LP - 1185 DO - 10.1136/ard.2004.033399 VL - 64 IS - 8 AU - T Dervieux AU - D Furst AU - D O Lein AU - R Capps AU - K Smith AU - J Caldwell AU - J Kremer Y1 - 2005/08/01 UR - http://ard.bmj.com/content/64/8/1180.abstract N2 - Objective: To investigate the contribution of red blood cell (RBC) methotrexate polyglutamates (MTX PGs), RBC folate polyglutamates (folate PGs), and a pharmacogenetic index to the clinical status of patients with rheumatoid arthritis treated with MTX.Methods: 226 adult patients treated with weekly MTX for more than 3 months were enrolled at three sites in a multicentred cross sectional observational study. Clinical status was assessed by the number of joint counts, physician’s global assessment of disease activity, and a modified Health Assessment Questionnaire (mHAQ). RBC MTX PG and folate PG metabolite levels were measured by high performance liquid chromatography fluorometry and radioassay, respectively. A composite pharmacogenetic index comprising low penetrance genetic polymorphisms in reduced folate carrier (RFC-1 G80A), AICAR transformylase (ATIC C347G), and thymidylate synthase (TSER*2/*3) was calculated. Statistical analyses were by multivariate linear regression with clinical measures as dependent variables and metabolite levels and the pharmacogenetic index as independent variables after adjustment for other covariates.Results: Multivariate analysis showed that lower RBC MTX PG levels (median 40 nmol/l) and a lower pharmacogenetic index (median 2) were associated with a higher number of joint counts, higher disease activity, and higher mHAQ (p<0.09). Multivariate analysis also established that higher RBC folate PG levels (median 1062 nmol/l) were associated with a higher number of tender and swollen joints after adjustment for RBC MTX PG levels and the pharmacogenetic index (p<0.05).Conclusion: Pharmacogenetic and metabolite measurements may be useful in optimising MTX treatment. Prospective studies are warranted to investigate the predictive value of these markers for MTX efficacy. ER -