The Effectiveness and Safety of Methotrexate as the First-Line Immunomodulator of Maintenance Therapy in Pediatric Crohn Disease

Abstract

Objectives: Methotrexate (MTX) has been used as maintenance therapy for Crohn disease (CD) in adults and children. However, there are only a few studies on the MTX's effectiveness in thiopurine-naïve CD adult patients and children. This study aimed to evaluate the MTX's effectiveness and safety as first immunomodulator for maintenance therapy in pediatric CD. Methods: This retrospective cohort study recruited 64 pediatric CD patients treated with MTX as a first-line immunomodulator. Clinical remission (CR) was assessed at weeks 14, 26, and 52. Mucosal healing (MH) was assessed at weeks 26 and 52. Results: Of 64 patients who received MTX, CR was noted in 60.9% at week 14, 29.7% with MH in 68.0% at week 26, and 27.8% with MH in 81.8% at week 52. When comparing age subtypes according to the Paris classification, the CR rate was higher in A1a than in the other subtypes at week 26 (60.0% in A1a, 26.5% in A1b, 0% in A2; P = 0.038). There were no differences in disease location, behavior, or perianal involvement. Adverse effects were noted in 30 of 64 (46.9%) patients, including 1 patient who stopped MTX before 26 weeks owing to side effects; increased liver enzymes in 25 (39.0%) patients, leukopenia in 5 (7.8%), nausea in 5 (7.8%), skin erosion in 1 (1.6%), and headache in 1 (1.6%). Conclusion: MTX as a first-line immunomodulator may be an effective and safe maintenance therapy for pediatric CD patients.

Editorial: Monitoring methotrexate polyglutamates in Crohn's disease—Authors' reply

“…The need for this trial is highlighted by increasing utilisation of MTX in paediatric CD. 8,9 To ensure a sufficiently large sample size, it may be prudent to conduct this trial initially within the RA population, given the broader use of MTX in RA.…”

“…Therefore, the next step in MTX TDM implementation could be a randomised controlled trial comparing standard‐of‐care dosing and TDM‐driven dosing. The need for this trial is highlighted by increasing utilisation of MTX in paediatric CD 8,9 . To ensure a sufficiently large sample size, it may be prudent to conduct this trial initially within the RA population, given the broader use of MTX in RA.…”