IN a new cross-sectional study, methotrexate intolerance in patients with rheumatoid arthritis (RA) was not significantly associated with dosing frequency or route of administration, according to new findings. These results may influence prescribing decisions for clinicians seeking to optimize methotrexate regimens based on patient comfort and tolerability.
The study evaluated 154 patients with RA, the majority of whom were female (89%) with a mean age of 50 years. All participants had received methotrexate for at least three months at an outpatient clinic. Investigators used the Methotrexate Intolerance Severity Score (MISS) and Health Assessment Questionnaire to assess tolerance, while also collecting demographic and clinical data through an electronic survey.
Among the patients, 64% were considered methotrexate-tolerant, while 36% reported a MISS of 6 or higher, indicating intolerance. Interestingly, patients in the intolerant group were significantly younger than those who tolerated the drug (mean age 47 vs. 54 years, p = 0.005), suggesting age may be a relevant factor in methotrexate tolerability. However, statistical analysis revealed no significant association between methotrexate intolerance and administration variables such as single vs. split weekly dosing or oral vs. subcutaneous delivery.
These findings challenge assumptions that modifying the method of administration can alleviate methotrexate intolerance. Clinicians may need to consider other factors, such as patient age or concurrent symptoms, when addressing intolerance, rather than relying solely on adjustments to delivery method or frequency.
The study’s authors emphasize that methotrexate remains central to RA management, but that intolerance remains a limiting factor. This research underscores the need for further studies into patient-specific factors influencing tolerability to guide personalized treatment approaches.
Reference:
Almalag HM et al. Factors related to dosing frequency and route of administration in methotrexate intolerance among patients with rheumatoid arthritis: a cross-sectional study. Ther Adv Drug Saf. 2025 Jun 14:16:20420986251349449.
