The Safety and Effectiveness of Early Anti-Tumor-Necrosis-Factor Therapy for Penetrating Crohn’s Disease Complications in Children

Background and Aims: Children with Crohn’s Disease (CD) who develop internally penetrating complications (IPCs; abscesses and inflammatory masses) are at high risk for surgery and other adverse events. Early anti-tumor-necrosis-factor therapy (anti-TNF) improves outcomes among children with CD and anti-TNF initiation soon after IPC resolution decreases surgical risk. We aimed to evaluate the safety and effectiveness of early anti-TNF therapy among children hospitalized with active IPCs. Methods: We conducted a multicenter retrospective study of children (age ≥6 years) diagnosed with IPCs from 2007-2021. The exposure was anti-TNF within 30 days of IPC diagnosis. Outcomes included 1) infectious serious adverse events (iSAE) within 90 days, 2) non-infectious CD-related SAE (cdSAE), 3) CD-related surgery, and 4) combined clinical-biochemical-corticosteroid-free remission within 1 year. Outcomes were compared via inverse-probability-of-treatment-weighted Kaplan-Meier curves (log-rank test) and Cox proportional hazards models stratified by percutaneous drainage (PD) status. Results: Among 203 patients (median age 16 years, 50% female), 87 (43%) received early anti-TNF within 30 days of IPC diagnosis. In Cox analyses, early anti-TNF was not linked to iSAE, cdSAE, or surgeries, but was associated with increased combined clinical-biochemical-corticosteroid-free remission (HR 1.65, 95%CI 1.20, 2.27). However, surgical risk differed by PD status: patients receiving early anti-TNF and PD had lower risk versus PD alone (event-free survival 58% versus 15%, log-rank P=0.04). Conclusions: Early anti-TNF therapy in children with IPCs was not associated with iSAE or cdSAE. Notably, in those undergoing PD, early anti-TNF was associated with decreased surgeries. These findings support early anti-TNF initiation within a multidisciplinary treatment framework. Prospective studies with standardized treatment protocols are needed.