High prevalence of methotrexate intolerance in rheumatoid arthritis patients: a cross-sectional study

Methotrexate (MTX) is the most commonly used disease-modifying antirheumatic drug (DMARD) for treating rheumatoid arthritis (RA). However, MTX use is associated with gastrointestinal adverse effects in a number of patients. Early detection of MTX intolerance could help modify the treatment strategy, thereby ensuring patient compliance and response. In the present study we aimed to identify the prevalence of MTX intolerance, and associated risk factors in a cohort of Indian RA patients receiving oral MTX therapy.

In this cross- sectional study, RA patients who were in regular use of oral or subcutaneous MTX for a minimum duration of three months were included. The participants were evaluated based on their responses to the methotrexate intolerance severity score (MISS) questionnaire. Patients with a MISS score ≥ 6 were considered MTX intolerant. Demographic data encompassing the patient’s age, sex, diet, MTX dosage, duration of use, route of administration, other medication, and disease activity assessed using the DAS-28 CRP was collected using a standardized patient history sheet.

Out of 200 adult RA patients, 86% were females with an average age of 49.25 ± 11.89 years, and the average duration of MTX use was 46.16 ± 53.40 months. A high prevalence of MTX intolerance (34.5%) was observed in RA patients. Nausea (85.5%) followed by abdominal discomfort (59.42%) were the most prevalent symptoms in intolerant patients. Furthermore, using multivariate analysis, we observed a positive association of MTX intolerance with female gender, disease severity, and MTX dose.

Although MTX is the one of the most commonly used medication for the treatment of RA, there is significant intolerance to this drug among adult RA patients. The symptoms observed not only occur after MTX intake but are also present before intake (anticipatory) and while thinking of taking MTX (associative). Our data indicates that a MTX dose of 15 mg/week or greater may be associated with intolerance. There is a need to objectively monitor RA patients to identify MTX intolerance early on to ensure mitigation steps for effective treatment response.