Comparative Effectiveness of Anti-TNF in Combination with Low Dose Methotrexate vs Anti-TNF Monotherapy in Pediatrics Crohn's Disease (COMBINE), United States, 2015-2022

The COMBINE study was a longitudinal examination of pediatric Crohn's Disease (CD) patients in the United States with data collected from 2015-2022. This study was a randomized, double blind, placebo controlled pragmatic trial to compare low dose oral methotrexate versus a placebo in children with Crohn's disease initiating anti-TNF (tumor necrosis factor) therapy with Infliximab or Adalimumab. Eligible participants were randomized with a 1:1 allocation and followed for a minimum of 12 months and maximum of 36 months in the context of routine clinical care. The primary outcome was a composite of indicators of treatment failure and/or toxicity. Secondary outcomes included patient reported outcomes of pain interference and fatigue.
Crohn's disease (CD) is a chronic inflammatory bowel disease (IBD) that affects approximately 600,000 Americans with estimated direct costs of $3.6 billion annually. Typical symptoms (e.g., abdominal pain, bloody diarrhea) result in substantial morbidity, including hospitalization and surgery, missed work and school, and diminished quality of life. The primary treatment goals for all CD patients are to induce remission by eradicating intestinal inflammation and related symptoms and maintain remission by preventing disease flares and progression. Additional treatment goals for pediatric CD include restoring physical and emotional development.