Dual Biological Therapy in Paediatric Population With Inflammatory Bowel Disease

Introduction: We aimed to assess the efficacy and safety of two biological therapies, anti-TNF (infliximab, adalimumab) vedolizumab and ustekinumab, in a refractory paediatric inflammatory bowel disease cohort. Methods: Twenty five children (18 ulcerative colitis (UC), 7 Crohn’s disease (CD) with a disease duration of 5,1 (1-13) years, initiated dual therapy at an age of 11,5 (3–17) years after failure of monotherapy with a biological drug. Eleven patient (44%) were treated with vedolizumab/adalimumab (VDZ + ADA), ten (40%) with ustekinumab/ adalimumab (UST + ADA), and three (12%) with infliximab/vedolizumab (IFX + VDZ). One patient (4%) initially treated with dual biological therapy in the regimen (VDZ + ADA), converted to treatment (UST + ADA) after 4 months of ineffective treatment. Results: A clinical improvement was obtained in eighteen children (72%; 11 UC; 7 CD) in PCDAI/PUCAI scale after 4 months of dose a second biological drug. The median PCDAI decreased from 52,5 points (35 – 65) to 12,5 points (0–30) in seven patients with Crohn's disease and PUCAI reduced from 45 points (0– 85) to 15 points (0-65) between baseline and 4 months in fifteen patients diagnosed with ulcerative colitis, who were treated for a minimum of 4 months. The median fecal calprotectin decreased from 1300 ug/g (53-10100) to 383 ug/g (5- 3410; P= 0,03) at the same time. Three patients (12%; 3UC) did not complete 4 months induction phase. One patient despite clinical improvement, dual biological therapy was discontinued because of anal abscess. (UC, VDZ + ADA). Another required a colectomy two months after starting therapy (UC, VDZ + IFX). Third patient had cardiac complications after suffering from Covid infection (UC, IFX + VDZ). Conclusion: Our clinical experience suggests that dual therapy may be an option for paediatric patients with moderate and severe courses of IBD with limited therapeutic options.