Authors (including presenting author) :
Lai WM, Cheung MS, HO CY, Lee KL, Jao HY, Tang CP, Lau J, Tsoi MH, Pang WC, Lee ZC, Lam YF, Ng ML
Affiliation :
Rheumatology Unit, Department of Medicine, Pamela Youde Nethersole Eastern Hospital
Keyword 1: :
Methotrexate intolerance
Keyword 2: :
evidence based management
Keyword 3: :
rheumatology
Introduction :
Methotrexate (MTX) is a first-line disease-modifying anti-rheumatic drug (DMARD) used to treat various rheumatological conditions. The most commonly reported adverse effect is gastrointestinal (GI) intolerance, manifesting as nausea, vomiting and loss of appetite, particularly in patients prescribed weekly doses ≥10mg. Current management of MTX-induced GI symptoms varies among clinicians, encompassing the use of symptomatic treatments (e.g., H2 blockers or proton pump inhibitors), dose reduction or instructing patients to split the weekly dose. This inconsistency in clinical practice highlights a gap in standardized, evidence-based management. A literature review was conducted to identify the best practices. Evidence indicates that a splint-dose regime of MTX can promise its efficacy while potentially alleviating GI symptoms, thereby enhancing medication adherence.
Objectives :
To evaluate the effectiveness of implementing a split-dose regimen of MTX in reducing GI side effects and improving drug compliance among rheumatology patients experiencing GI intolerance.
Methodology :
A prospective study was conducted with patients recruited from the PYNEH rheumatology nurse clinic between June 2025 and December 2025. Inclusion Criteria: 1.Patients prescribed MTX ≥10mg per week who reported recurrent GI intolerance. Exclusion Criteria: 1.Patients unable to follow education instructions, such as those with unstable psychiatric conditions or mental incompetence. Eligible patients received standardized education from rheumatology nurses on administering their weekly MTX dose as two separate doses, taken eight hours apart. The effectiveness of this approach was assessed after 4-6 weeks using patient-reported outcome (PRO) measures. Data were collected via questionnaires during follow-up nurse clinic visits or structured telephone interviews conducted by rheumatology nurses.
Result & Outcome :
A total of 21 rheumatology patients, aged 28-78 years, were enrolled. •Adoption of Split Dosing: 85% (n=18) of patients adopted the split-dose regimen following education. Two patients declined participation as their GI symptoms had already resolved and one patient had self-discontinued. •Perceived Efficacy and Side Effects: No patients expressed concern that dose splitting compromised drug efficacy. All patients implementing the split-dose regime reported a reduction in GI side effects. •Medication Adherence: Among the recruited patients, 52% reported having self-adjusted their MTX dosage previously due to GI intolerance. These patients indicated improved medication compliance following the initiation of the split-dose schedule. Conclusion: Implementing a split-dose regimen of Methotrexate for rheumatology patients with GI intolerance is an effective strategy for reducing GI side effects and enhancing medication compliance. These findings support incorporating split-dose administration into standard practice within rheumatology clinics to improve patient outcomes and treatment adherence.
