Hepatotoxicity From Disease-Modifying Anti-rheumatic Drugs (DMARDs) and Association With Metabolic Syndrome in Rheumatoid Arthritis.

Objectives: Hepatotoxicity is a frequent reason why disease-modifying anti-rheumatic drugs (DMARDs) are stopped or changed. We hypothesize that features of metabolic syndrome (such as obesity, dyslipidemia, and diabetes) are risk factors for hepatotoxicity leading to DMARD change in rheumatoid arthritis (RA).

Methods:  We conducted a retrospective chart review of 361 patients with RA. Demographic information, lipid panels, smoking status, prior alcohol use, BMI, statin use, seropositive status, viral hepatitis serologies, and type of DMARD use were noted at the initial visit and at the time of DMARD change due to hepatotoxicity if applicable. Using exact logistic regression, odds ratios for the risk factors of DMARD change due to hepatotoxicity (primary outcome) were calculated.

Results: Twenty out of 361 patients with RA had their DMARD changed due to hepatotoxicity. Methotrexate (odds ratio {OR} 3.07) and leflunomide (OR 6.11) carried the highest OR for DMARD change. BMI > 35 (OR 2.14), diabetes mellitus II (OR 2.01), and alcohol abuse (OR 3.5) were associated with DMARD change due to hepatotoxicity but were not statistically significant. Rheumatoid factor or anti-CCP seropositivity did not appear to be associated with increased risk for the primary outcome.

Conclusion: Our study does suggest that several surrogates of metabolic syndrome may be associated with the risk of hepatotoxicity due to methotrexate and leflunomide. Though the study was underpowered to assess the risk for glycated hemoglobin (HbA1c) and obesity, these variables did trend toward increasing the risk. Clinicians should consider features of metabolic syndrome as potential risk factors for hepatotoxicity with DMARD use.