Methotrexate for the Treatment of Pediatric Crohn's Disease: A Systematic Review and Meta-analysis

Background: Methotrexate (MTX) is an immunomodulator used for the treatment of pediatric inflammatory bowel disease (IBD). There are currently no RCTs that assess the treatment efficacy of methotrexate within the pediatric IBD patient population. This systematic review and meta-analysis assesses the efficacy of MTX therapy among the existing pediatric literature. Methods: A systematic literature search was performed using MEDLINE and the Cochrane library from inception until March 2016. Synonyms for 'pediatric', 'methotrexate' and 'IBD' were utilized as both free text and MESH search terms. The studies included contained clinical remission (CR) rates for MTX treatment of pediatric IBD patients 18 yrs old, as mono-or combination therapy. Case studies with < 10 patients were excluded. Quality assessment was performed with the Newcastle-Ottawa Scale. Meta-analysis calculated pooled CR rates. A random-effects meta-analysis with forest plots was performed using R. Results: Fourteen (11 monotherapy, 1 combination therapy, 2 both; n = 886 patients) observational studies were eligible out of 202 studies. No interventional studies were identified. The pooled achieved CR rate for pediatric CD patients on monotherapy within 3-6 months was 57.7% (95% CI 48.2-66.6%), (P = 0.22; I-2 = 29.8%). The CR was 37.1% (95% CI 29.5-45.5%), (P = 0.20; I-2 = 37.4%) for maintenance therapy at 12 months. Sub-analysis could not identify CR differences between MTX administration types, thiopurine exposure. Conclusions: This meta-analysis demonstrated that, over 50% of pediatric Crohn's disease patients induced with methotrexate achieved clinical remission, while 12-month remission rate was only 37%. Prospective controlled interventional trials should assess treatment efficacy among patient subgroups.