Adalimumab Therapy in Pediatric Crohn Disease

Objectives: European Crohn’s Colitis Organization (ECCO) and the European Society of Pediatric Gastroenterology, Hepatology and Nutrition (ESPGHAN) guidelines recommend the early use of anti‐tumor necrosis factor (TNF) biologicals in pediatric Crohn disease (CD) patients with positive predictors for poor outcome. The objective of the present study was to compare early “Top‐Down” use of adalimumab (ADA) immunomodulator/biologics‐naive patients to conventional “Step‐Up” management. Methods: One hundred and twenty consecutive patients with a confirmed diagnosis of CD and treated with ADA between 2008 and 2019 were included and allocated to the ADA‐Top Down (n = 59) or ADA‐Step Up group (n = 61). The primary endpoint was prolonged steroid‐/enteral nutrition‐free clinical remission at 24 months, defined by a weighted Pediatric Crohn’s Disease Activity Index (wPCDAI) < 12.5. Clinical and biological data were collected at 12 and 24 months. Results: At start of ADA, disease activity was comparable between the ADA‐Top Down group and the ADA‐Step Up group (wPCDAI = 31 ± 16 vs 31.3 ± 15.2, respectively, P = 0.84). At 24 months, the remission rate was significantly higher in the ADA‐Top Down group (73% vs 51%, P < 0.01). After propensity score, the Top‐Down strategy is still more effective than the Step‐Up strategy in maintaining remission at 24 months [hazard ratio (HR) = 0.36, 95% CI (0.15–0.87), P = 0.02]. Patients in the ADA‐Top Down group were mainly on monotherapy compared to patients in the ADA‐Step Up group (53/55 vs 28/55 respectively, P < 0.001). Serum levels of ADA were higher in the ADA‐Top Down group than in the ADA‐Step Up group (12.8 ± 4.3 vs 10.4 ± 3.9 µg/mL, respectively, P < 0.01). There were no serious adverse events. Conclusions: Early use of ADA appears to be more effective in maintaining relapse‐free remission at 2 years, while using it as monotherapy. These findings further favor the recommendation of early anti‐TNF use in high‐risk CD patients.