Adherence to methotrexate safety guidelines in rheumatoid arthritis: real-world evidence from South Africa’s public health system

Abstract

What is Known and Objective?: Methotrexate (MTX) is the cornerstone therapy for rheumatoid arthritis (RA) but is associated with potential haematologic and hepatic toxicities. In South Africa, treatment guidelines emphasise regular laboratory monitoring and folic acid supplementation to enhance treatment safety and reduce adverse effects. This study evaluates the implementation of these safety measures in a resource-constrained public health setting. Methods: A retrospective review of electronic health records was conducted for adult RA patients (≥ 18 years) who had been prescribed oral MTX for at least six months in the Western Cape Province between January and December 2022. Data collected included patient demographics, MTX and folic acid prescriptions, laboratory test results (white cell count [WCC], platelet count [PLT] and alanine aminotransferase [ALT]) and comedications. Laboratory abnormalities were classified according to the WHO reference ranges. Correlation analysis assessed associations between MTX/folic acid doses and laboratory values. Results and Discussion: Among 820 patients included in the study (82.1% female, mean age 55 ± 13 years), 94.9% were prescribed folic acid at the initiation of MTX and 96.2% at their most recent visit. Monitoring adherence improved over time: At MTX initiation, 71.8% had baseline WCC/PLT and 72.2% had ALT records; within 6 months of the last visit, over 88% had follow-up laboratory results. Most patients had normal laboratory results at follow-up (WCC: 85.9%; PLT: 73.8%; ALT: 90.4%). Spearman’s correlation analysis did not identify significant associations between MTX/folic acid dose and laboratory values, likely reflecting narrow dose ranges and limited subgroup size. These findings highlight the success of safety monitoring practices and the coprescription of folic acid in reducing the risks associated with MTX. What is New and the Conclusion?: This study demonstrates that MTX safety monitoring and folic acid supplementation are well integrated into public RA care in South Africa, with a low incidence of laboratory abnormalities. Our exploratory correlation analysis did not identify significant associations between MTX/folic acid dose and laboratory values; however, this likely reflects narrow dose ranges and limited subgroup data rather than the absence of effect. These findings highlight the success of current safety practices while underscoring the need for larger, prospective studies to better characterise dose–toxicity relationships.