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Leflunomide increases the risk of silent liver fibrosis in patients with rheumatoid arthritis receiving methotrexate

 Sang-Won Lee  ;  Hee-Jin Park  ;  Beom Kyung Kim  ;  Kwang-Hyub Han  ;  Soo-Kon Leee  ;  Seung Up Kim  ;  Yong-Beom Park 
 ARTHRITIS RESEARCH & THERAPY, Vol.14(5) : 232, 2012 
Journal Title
Issue Date
Antirheumatic Agents/adverse effects* ; Antirheumatic Agents/therapeutic use* ; Arthritis, Rheumatoid/drug therapy* ; Cross-Sectional Studies ; Dose-Response Relationship, Drug ; Drug Therapy, Combination ; Elasticity Imaging Techniques ; Female ; Humans ; Isoxazoles/adverse effects* ; Isoxazoles/therapeutic use* ; Liver/diagnostic imaging ; Liver/physiopathology ; Liver Cirrhosis/diagnosis ; Liver Cirrhosis/epidemiology* ; Liver Cirrhosis/physiopathology ; Male ; Methotrexate/therapeutic use* ; Middle Aged ; Multivariate Analysis ; Risk Factors
Rheumatoid Arthritis ; Rheumatoid Arthritis Patient ; Chronic Liver Disease ; Liver Fibrosis ; Cumulative Dose
ABSTRACT: INTRODUCTION: We identified silent liver fibrosis in patients with rheumatoid arthritis (RA) using transient elastography, and investigated medication that correlated with abnormal liver stiffness measurement (LSM) values. METHODS: We consecutively enrolled 105 patients with RA taking methotrexate over 24 weeks with normal liver functions and no history of underlying chronic liver disease. Blood tests were performed, and body mass index and metabolic syndrome were assessed. We checked LSM values, and adopted 5.3 kPa as the cutoff for abnormal LSM values. The cumulative doses of medications including methotrexate, leflunomide, sulfasalazine, hydroxychloroquine, prednisolone, meloxicam, and celecoxib were calculated. RESULTS: The median age of patients (20 men and 85 women) was 52.4 years. The median LSM value was 4.7 kPa and 24 (22.9%) patients had abnormal LSM values. Gamma-glutamyltranspeptidase levels and the cumulative doses of leflunomide and prednisolone significantly correlated with LSM values (P<0.05). The cumulative dose of leflunomide, but not methotrexate, was significantly higher in patients with abnormal LSM values than that in patients with normal LSM values (P = 0.008). When RA patients receiving leflunomide plus methotrexate were classified into two groups according to the optimal cutoff cumulative dose of leflunomide (19,170 mg), abnormal LSM values were more frequently identified in patients with high cumulative dose of leflunomide (odds ratio, 12.750; P<0.001). CONCLUSIONS: The cumulative dose of leflunomide was the only independent predictor of abnormal LSM values in patients with RA who had received methotrexate for more than six months.
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1. College of Medicine (의과대학) > Dept. of Internal Medicine (내과학교실) > 1. Journal Papers
Yonsei Authors
Kim, Beom Kyung(김범경) ORCID logo https://orcid.org/0000-0002-5363-2496
Kim, Seung Up(김승업) ORCID logo https://orcid.org/0000-0002-9658-8050
Park, Yong Beom(박용범)
Park, Hee Jin(박희진)
Lee, Sang Won(이상원) ORCID logo https://orcid.org/0000-0002-8038-3341
Lee, Soo Kon(이수곤)
Han, Kwang-Hyub(한광협) ORCID logo https://orcid.org/0000-0003-3960-6539
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