Risk factors for methotrexate-induced abnormal laboratory monitoring results in patients with rheumatoid arthritis

Objective. To determine risk factors for methotrexate (MTX)-induced hepatic and hematologic laboratory abnormalities in patients with rheumatoid arthritis (RA). Methods. Measurements of aspartate aminotransferase (AST), white blood cell counts, and platelet counts were collected in a database of patients with RA receiving MTX from 1991 through 2002. Potential risk factors for toxicity were recorded on each patient. Results. Four hundred and eighty-one patients were followed for 2,323 person-years of MTX exposure. MTX was discontinued permanently because of abnormal laboratory test results in 22 patients (4.6%), the majority of whom (17/22, 77%) had elevated AST values. The body mass index (BMI) was significantly higher in those patients where MTX was permanently discontinued than in those in whom it was not (p < 0.03). Independent predictors of a significantly higher percentage of abnormal AST values were lack of folate supplementation (p < 0.001) and untreated hyperlipidemia (p < 0.02). Of the 17 patients in whom MTX was discontinued permanently because of an elevated AST value, 11/17 (65%) had either lack of folate supplementation or untreated hyperlipidemia. Hypoalbuminemia correlated independently with an increased percentage of abnormal platelet counts (p < 0.03). Conclusion. Lack of folate supplementation, untreated hyperlipidemia, and elevated BMI identified patients receiving MTX at risk for transaminase elevation, and low serum albumin was a risk factor for thrombocytopenia. Nonalcoholic fatty liver disease could be the underlying risk factor for transaminase elevation in patients with hyperlipidemia and obesity.