Leflunomide increases the risk of silent liver fibrosis in patients with rheumatoid arthritis receiving methotrexateReport as inadecuate

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Arthritis Research and Therapy

, 14:R232

First Online: 29 October 2012Received: 23 May 2012Revised: 14 September 2012Accepted: 25 October 2012


IntroductionWe 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.

MethodsWe 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.

ResultsThe 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.

ConclusionsThe 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.

AbbreviationsALPalkaline phosphatase

ALTalanine aminotransferase

ASTaspartate aminotransferase

AUROCarea under the receiver operator characteristic curve

BMIbody mass index

DMARDdisease-modifying anti-rheumatic drug


HDLhigh density lipoprotein

INRinternational normalized ratio


LSMliver stiffness measurement


NSAIDnon-steroidal anti-inflammatory drug

ORodds ratio

RArheumatoid arthritis

TNFtumor necrosis factor.

Electronic supplementary materialThe online version of this article doi:10.1186-ar4075 contains supplementary material, which is available to authorized users.

Seung Up Kim and Yong-Beom Park contributed equally to this work.

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Author: Sang-Won Lee - Hee-Jin Park - Beom Kyung Kim - Kwang-Hyub Han - Soo-Kon Lee - Seung Up Kim - Yong-Beom Park

Source: https://link.springer.com/

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