Work

Methotrexate and malignancy in rheumatoid arthritis: Evidence, risks, and clinical considerations

Year: 2026

Type: review

Abstract: In this review, we summarized the current evidence on the risks of incident malignancy and cancer recurrence in patients with rheumatoid arthritis (RA) treated with methotrexate (MTX). Before considering the effect of MTX, it is important to recognize the malignancy risk associated with RA itself. The overall risk of malignancy in patients with RA modestly increased, as per two meta-analyses, although Japanese studies report inconsistent findings, with one showing a slight decrease and another a slight increase. The risk of malignant lymphoma is increased, whereas the risk of colorectal cancer appears to be reduced. Additionally, there are concerns regarding the increased risk of lung and skin cancers. However, there is limited evidence specific to patients with RA treated with MTX. According to an Australian report, these patients have a higher risk of overall malignancy, along with an increased risk of malignant lymphoma, lung cancer, and melanoma. Studies comparing MTX with tumour necrosis factor inhibitors have reported no significant difference in the overall malignancy risk or increased malignancy risk. In White patients, MTX has been associated with an increased risk of recurrence in patients with RA and a history of non-melanoma skin cancer. There is insufficient evidence regarding the risks of MTX use in patients with RA and malignancy. Therefore, decisions regarding MTX use should be made individually based on shared decision-making, and careful follow-up is necessary.

Source: Modern Rheumatology

DOI: 10.1093/mr/roag080