Methotrexate for the Management of Crohn's Disease in Children

To review the literature evaluating methotrexate as a treatment option for Crohn's disease (CD) in pediatric patients.

A search of PubMed electronic database (1966 to August 2015) and secondary resources was performed using the terms methotrexate, Crohn's, and inflammatory bowel disease. Other relevant articles cited within identified articles were also utilized.

Data sources were limited to English-language studies that included children less than 18 years of age. In total, 10 clinical studies met the criteria.

Awareness of the risk of hepatosplenic T-cell lymphoma associated with anti-tumor necrosis factor and thiopurine therapies has renewed interest in methotrexate to treat CD in children. According to data from 10 predominantly retrospective studies, children treated with oral or subcutaneous methotrexate once weekly had remission rates of 25% to 53% at 1 year. Adverse effects most often included nausea and vomiting, elevated liver function tests, headache, and hematological toxicity. The evidence to support methotrexate is limited by inconsistent study design and poorly described dosage regimens. It has been most frequently evaluated in patients with prior thiopurine exposure and has not been thoroughly evaluated as first-line therapy.

Based on results of retrospective studies, methotrexate is useful in the treatment of pediatric CD in those who fail thiopurine therapy. Remission rates with methotrexate are similar to those for thiopurine therapy, although no studies directly compare these agents. Although preliminary results are promising, prospective studies are needed to assess the use of methotrexate as initial first-line therapy in the pediatric CD population.