Risk Factors Associated with Methotrexate Intolerance in Rheumatoid Arthritis Patients

Haya Almalag,1 Hanan H Abouzaid,1 Lamya Alnaim,1 Jawza Albaqami,1 Rawan Al Shalhoub,1 Ibrahim Almaghlouth,2,3 Maha Dessougi,4 Amal Al Harthi,4 Mohamed Bedaiwi,2 Eman Alfi,5 Mohammed A Omair2 1Department of Clinical Pharmacy, College of Pharmacy, King Saud University, Riyadh, Saudi Arabia; 2Rheumatology Unit, Department of Medicine, King Saud University Medical City, Riyadh, Saudi Arabia; 3College of Medicine Research Centre, King Saud University, Riyadh, Saudi Arabia; 4Rheumatology Department, Security Force Hospital, Riyadh, Saudi Arabia; 5Clinical Pharmacy Department, Pharmaceutical Services, King Saud University Medical City, Riyadh, Saudi ArabiaCorrespondence: Haya Almalag Department of Clinical PharmacyCollege of Pharmacy, King Saud University, Riyadh 11149, Saudi ArabiaTel +966 118057859Email halmalaq@ksu.edu.saBackground: 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