Dual Biologic Therapy in Inflammatory Bowel Disease, a Retrospective Cohort Study of Vedolizumab and Anti-Tumor Necrosis Factor Alpha Therapy in Children.

OBJECTIVES:Despite advances in pediatric inflammatory bowel disease (PIBD) with biologics, remission rates remain at 47%-60% with loss-of-response rates at 60%-68%. Evidence for efficacy of dual biologic therapy (DBT) with anti-tumor necrosis factor alpha therapy (anti-TNF-α)- vedolizumab (VDZ) for children refractory to anti-TNF-α therapy is limited. This study aimed to describe rates of steroid-free clinical remission (CR), endoscopic and histological remission, trends in biochemistry, predictors of response, and adverse events in this population. METHODS:We performed a retrospective study of children with PIBD treated with anti-TNF-α-VDZ DBT for 6-12 months from 2020 to 2023. RESULTS:Twenty-two treatment episodes were analyzed in 21 patients (17 Crohn's disease, 5 ulcerative colitis) with 13 continuing to 12 months. CR increased from 9% at baseline to 68% at 3 months (95% confidence interval [CI] 47%-83%, p < 0.01), 55% at 6 months (95% CI 35%-73%, p < 0.05) and 50% at 12 months (95% CI 31%-69%, p < 0.05). Seventy-two percent in total achieved CR during follow-up. Endoscopic remission increased from 5% to 38% (p = 0.02), histological remission from 5% to 29% (p = 0.046). Fecal calprotectin decreased from 930 to 500 μg/g at 3 months (p = 0.04), 680 μg/g at 6 months (p = 0.03), and 255 μg/g at 12 months (p = 0.12). Trends toward remission were observed in patients with colonic disease, incomplete response rather than loss of response to anti-TNF-α, and ulcerative colitis. Two significant adverse events occurred: pulmonary mucormycosis and herpes-simplex virus keratitis. CONCLUSION:Anti-TNF-α-VDZ DBT improved clinical, endoscopic, and histological outcomes in children refractory to biologic monotherapy.