A NEW cross-sectional study has revealed that over one-third of adult patients with rheumatoid arthritis (RA) in India experience intolerance to methotrexate (MTX), the most widely prescribed disease-modifying antirheumatic drug (DMARD). Conducted on a cohort of 200 RA patients, the study found a striking 34.5% prevalence of MTX intolerance, with symptoms like nausea (85.5%) and abdominal discomfort (59.4%) being most common.
Using the validated Methotrexate Intolerance Severity Score (MISS), researchers identified not only post-dose symptoms but also anticipatory and associative symptoms—where patients experience discomfort even before taking the medication or when merely thinking about it. This psychological dimension of intolerance has critical implications for long-term adherence and disease control.
The study also found that female gender, higher MTX dosage (≥15 mg/week), and greater disease activity were significantly associated with intolerance. Given that 86% of the participants were female with a mean age of 49, the findings highlight an urgent need for individualized treatment plans in this demographic.
“These findings underscore the importance of early detection and regular monitoring for MTX intolerance,” the authors state. “Identifying patients at risk could allow for timely dose adjustments, switching administration routes, or supportive interventions to improve adherence.”
The study serves as a wake-up call for clinicians treating RA in similar resource-limited settings, where methotrexate remains a cornerstone therapy due to its affordability. Introducing standardized intolerance screening tools like the MISS questionnaire into routine care could help bridge the gap between effective treatment and patient tolerability—ultimately improving both quality of life and clinical outcomes.
Reference
Nalwa HS et al. High prevalence of methotrexate intolerance in rheumatoid arthritis patients: a cross-sectional study. BMC Rheumatol. 2025;DOI: 10.1186/s41927-025-00466-2.
