Patient perspectives on simultaneous methotrexate-folic acid intake to improve adherence in rheumatoid arthritis: a cross-sectional survey

Abstract Objective To assess real-world adherence to folic acid supplementation with methotrexate and patient perceptions of a simplified, same-day dosing strategy in rheumatoid arthritis. Methods We conducted a cross-sectional online survey co-designed with patient representatives and distributed by the French patient association AFPric. Rheumatoid arthritis patients treated with methotrexate were eligible. The questionnaire captured methotrexate and folic acid regimens, omissions, adverse events, and attitudes toward same-day methotrexate and folic acid administration. Analyses were descriptive with prespecified subgroup comparisons. Results Among 967 respondents (86.8% women; mean age 62.4 years), 86.7% reported once-weekly folic acid supplementation. Overall, 25.5% reported at least occasional folic acid omission, with omissions more frequent among long-term methotrexate users. Nausea after methotrexate was reported by 46.6% of respondents and by 52.6% of those reporting folic acid omissions. A same-day methotrexate and folic acid regimen was perceived as simpler by 30.5%, while 41.5% believed it could reduce folic acid omission. Overall, 64.8% indicated that they would be willing to participate in a randomised controlled trial evaluating simultaneous administration. Conclusion One in four people with rheumatoid arthritis treated with methotrexate reported folic acid omissions. Many respondents believed that a same-day regimen could reduce folic acid omissions, and interest in participating in a clinical trial was high. These findings support the feasibility of prospectively evaluating whether same-day methotrexate and folic acid administration may improve adherence and tolerability in selected patients, particularly those receiving once-weekly folic acid supplementation, without compromising methotrexate effectiveness.