Methotrexate toxicity in patients with rheumatic diseases: A 10-year evaluation of manifestations, risk factors, and mortality

Abstract

Methotrexate (MTX) is a commonly used medication in the treatment of rheumatic diseases. MTX toxicity is a serious and at times fatal complication. In this 10-year cohort, we retrospectively evaluated the cases of MTX toxicity among rheumatic patients to identify demographic, clinical, and laboratory characteristics and risk factors of mortality. Through 10 years, patients older than 17 years with a rheumatic disease and at least one major manifestation of MTX toxicity (mucositis, myelosuppression, pneumonitis) were enrolled in the study. Demographic, clinical, and laboratory data were collected. Comparisons were made between patients who recovered and those who passed away. Of the 66 patients, most had rheumatoid arthritis, followed by systemic lupus erythematous. Most patients were females, and their mean age was 63.3±12.4 years. The most common comorbidity was hypertension followed by diabetes mellitus. Most patients were on polypharmacy and were taking MTX incorrectly. Other potential risk factors of toxicity were hypoalbuminemia, decreased renal function, and infection. The outcome of six patients was death and the predictors of mortality were severe leukopenia at admission, infection, especially sepsis, and severe renal impairment. In this study, we observed some potential risk factors for toxicity, namely incorrect MTX use, polypharmacy, renal impairment, hypoalbuminemia, infection, and comorbid conditions such as diabetes mellitus, hypertension, and ischemic heart disease. We also identified the risk factors of mortality, including infection, sepsis, severe leukopenia, high creatinine levels, and severe renal impairment.