Intolerance of oral methotrexate in juvenile idiopathic arthritis

Area of Science:

• Pediatric Rheumatology
• Pharmacology
• Clinical Trials

Background:

• Oral methotrexate (MTX) is a primary therapy for juvenile idiopathic arthritis (JIA).
• Adverse events (AEs), particularly nausea and vomiting, frequently compromise MTX adherence and efficacy in JIA patients.
• Understanding MTX intolerability is crucial for optimizing JIA management.

Purpose of the Study:

• To evaluate the incidence and impact of oral methotrexate (MTX) intolerability in patients with juvenile idiopathic arthritis (JIA).
• To identify common adverse events (AEs) associated with MTX treatment in JIA.
• To assess the consequences of MTX intolerability on treatment outcomes, including remission and the need for biologic agents.

Main Methods:

• Retrospective analysis of 52 juvenile idiopathic arthritis (JIA) patients treated with oral methotrexate (MTX) between April 2011 and October 2022.
• Dose adherence to Japanese clinical guidelines (target 10 mg/m²/week, max 16 mg/week) was assessed.
• Incidence of AEs, specific symptoms, impact on remission, and need for biologics were recorded.

Main Results:

• 68% of patients experienced AEs, with nausea and vomiting being most frequent (42% within 6 months, 67% within 12 months).
• 29% of patients could not tolerate the target MTX dose due to AEs.
• 21% failed to achieve or maintain remission due to MTX-related nausea/vomiting, with 17% requiring biologics.

Conclusions:

• Oral methotrexate (MTX) intolerability is a significant issue in juvenile idiopathic arthritis (JIA), affecting nearly two-thirds of patients.
• Nausea and vomiting are common AEs that can lead to treatment failure, loss of remission, and escalation to biologic therapies.
• MTX intolerability substantially impacts treatment outcomes and necessitates careful monitoring and management strategies in JIA.