Is combining methotrexate and leflunomide a safe option for treating rheumatoid arthritis?

Rheumatoid arthritis (RA) is a chronic immune-mediated disease marked by synovial inflammation and systemic features. Early management typically relies on conventional synthetic disease-modifying antirheumatic drugs (csDMARDs), with methotrexate (Mtx) serving as the primary therapeutic agent. When Mtx is contraindicated, leflunomide (Lef) can be used as a treatment strategy. There are concerns about hepatotoxicity, cytopenia, pneumonia, and increased risk of infection when these therapies are combined. In this study, we aimed to evaluate the side effects and treatment duration of the Mtx/Lef combination in patients with RA. All patients admitted to the Rheumatology clinic between 2016 and 2023 and diagnosed with RA were retrospectively reviewed. Patients who received Mtx/Lef combination therapy during this period were identified. The data for patients who continued Mtx/Lef combination therapy were recorded at the last visit, and those who discontinued the combination therapy were recorded at the visit of discontinuation. Adverse effects associated with Mtx/Lef combination therapy were assessed through retrospective review of clinical follow-up notes, laboratory test results, and drug safety monitoring forms. Adverse events leading to treatment discontinuation were classified as either due to side effects or lack of therapeutic response. This study was conducted with a total of 222 participants, comprising 184 females (82.9%) and 38 males (17.1%). No side effects were observed in 141 (63.5%) patients after Mtx/Lef use. Gastrointestinal system side effects were observed in 16.7% of the participants, followed by elevated liver function tests in 11.3%. It was determined that 55% of the participants were unable to continue treatment due to treatment ineffectiveness or side effects. Our study results offer a good safety profile and long-term drug survival. Survival in long-term treatment may contribute to reducing treatment costs.