Background Methotrexate (MTX) is the first line therapy for treatment of rheumatoid arthritis (RA) because of high efficacy and saved cost. MTX has toxicities such as GI irritation, hepatitis, pneumonitis and cytopenia. However, MTX toxicities usually mild and does not lead to discontinuation. MTX toxicities have never been studied in Thailand, which prevalence of hepatitis B infection was high (26%).
Objectives To examine the prevalence and reasons of discontinuation of MTX in RA and to determine factors, especially previous hepatitis B infection, associated with MTX discontinuation.
Methods All 197 RA patients according to American College of Rheumatology (ACR) 1987 and/or ACR and European league of Rheumatology 2010 between 2000 and 2015 were studied. Anti-hepatitis B core antibody (anti-HBcAb), hepatitis B surface antigen (HBsAg), chest film were revealed prior to start methotrexate. Patients with positive HBsAg were excluded. Measurements of aspartate aminotransferase (AST), alanine aminotransferase (ALT), complete blood counts, signs and symptoms of methotrexate toxicities were recorded. Potential risk factors for toxicity were recorded. Univariable and multivariated analyses were performed to identify associated factors for permanently discontinuation of MTX.
Results One hundred and ninety-seven RA patients were followed for 2142 person-years of MTX exposure. MTX was discontinued permanently in 47 patients (24%). Reasons for discontinuation were as followed: leucopenia 12 patients (26%), anemia8 patients (17%), thrombocytopenia3 patients (6%), pneumoitis11 patients (23%), GI irritation8 patients (17%), mild hepatitis (AST40–80 IU/mL) 8 patients (17%), severe hepatitis (AST>80 IU/mL) 8 patients (17%), mucositis 5 patients (10%), alopecia1 patient (2%). Mean time (standard deviation) to discontinuation was 522 (26.9) days. Multivariate logistic regression analyses found that serum albumin level less than 3.5 mg/dL, leflunomide use of more than 10 mg/d and prednisolone use of more than 10 mg per day were significantly associated with methotrexate discontinuation (odd ratio and 95% confidence interval of 15.33 (1.37–171.23), 5.33 (1.40–20.27)2.97 (1.14–7.77), respectively). Previous resolved hepatitis B infection defined as patients with positive anti-HBcAb was not associated with methotrexate discontinuation.
Conclusions MTX discontinuation occurred in almost one-fourth of patients. Low serum albumin, glucocorticoid and leflunomide use were associated with permanent discontinuation of methotrexate in patients with rheumatoid arthritis.
Chongsrisawat V et al., Tropical Medicine and International Health. doi: 10.1111/j.1365-3156.2006.01709.x Volume 11 no 10 pp 1496–1502 October 2006
Tropical Medicine and International Health. volume 11 no 10 pp 1496–1502 October 2006.
Disclosure of Interest None declared