Risk Factors Associated with Methotrexate Intolerance in Rheumatoid Arthritis Patients

Abstract

Background

Methotrexate (MTX) Intolerance Severity Score (MISS) has been previously validated in the Arabic language and has helped to detect high levels of intolerance in rheumatoid arthritis (RA) patients. The aim of the current study was to evaluate patient and disease characteristics associated with a high risk of MTX intolerance.

Materials and Methods

A cross-sectional interview-based survey was conducted using adult RA patients as a study group, who were visiting a specialized rheumatology clinic at King Saud University Medical City. The Arabic MISS was used in this survey. Statistical analyses were performed to understand associations between MTX-intolerant and MTX-tolerant patients.

Results

A total of 117 patients were involved in this study. Of those, 101 (86.3%) were females with a mean (SD) disease duration of 6.6 (5.7) years. The median (interquartile range (IQR)) Disease Activity Score-28 (DAS28) was 3.6 (3.6–4.1). MTX intolerance was observed in 55 (47%) patients. The most predominant component in patients with a positive test was the behavioral component. Intolerant patients had a higher median of pain (47.3 vs. 50.0; P = 0.010) and patient global assessment (50.0 vs. 60.0; P = 0.004) scales compared to those in tolerant patients. Additionally, MTX intolerance was associated with the female gender (adjusted odds ratio (AOR) 6.724; 95% CI 1.420, 31.843, P = 0.016), marital status (AOR 2.549; 95% CI 1.037, 6.270, P = 0.042) and DAS28 (AOR 1.612; 95% CI 1.032, 2.517, P = 0.036). There was no significant difference between the two groups in the remaining disease activity parameters, background therapies, seropositivity, and smoking status (P > 0.05).

Conclusion

Patient characteristics, rather than disease activity, significantly impact MTX intolerance. Behavioral component is the main driver of intolerance. Intolerant patients have higher patient-reported outcomes. Qualitative studies are needed to explore causes and potential solutions to MTX intolerance.

Keywords:

• methotrexate
• rheumatoid arthritis
• intolerance

Acknowledgments

This research project was supported by a grant from the “Research Center of the Female Scientific and Medical Colleges,” Deanship of Scientific Research, King Saud University.

Data Sharing Statement

The datasets used and/or analyzed during the current study are available from the corresponding author upon reasonable request.

Ethics Approval and Informed Consent

Institutional review board acceptance from King Saud University Medical City was obtained (Number E-17-2396) and included patients signed an informed consent after the investigators discussed the research with the patient.

Consent for Publication

Written informed consent was obtained from study participants.

Author Contributions

All authors contributed extensively to the work presented in this paper, have drafted or substantially revised the article, reviewed the final manuscript, agree to take responsibility for the content of the article and have approved the manuscript and agree with its submission to Open Access Rheumatology: Research and Reviews. All authors contributed towards data analysis, drafting and critically revising the paper, gave final approval of the version to be published, and agreed to be accountable for all aspects of the work.

Disclosure

The authors report no conflicts of interest for this work.