Magdalena Wlazło

Objectives: The severe course of inflammatory bowel diseases (IBDs) refractory to advanced therapies in children results in the search for new therapeutic methods. The aim of this study was to evaluate the efficacy and safety of dual therapy with biologics in a cohort of children with IBD.Methods: Retrospective analysis of data from 29 children with a diagnosis of IBD, 19 with ulcerative colitis (66%), 10 with Crohn's disease (CD) (34%) qualified for dual biological therapy (DBT). The median age of patients was five (interquartile range [IQR], 1–15) years at diagnosis of IBD and 14 (IQR, 3–17) years at eligibility for dual therapy. Thirteen (45%) patients were treated with vedolizumab/adalimumab (VDZ + ADA), 13 (45%) with ustekinumab/adalimumab (UST + ADA), three (10%) with infliximab/vedolizumab (IFX + VDZ).Results: Clinical remission was achieved in 13 (45%; seven UC and six CD) and 12 (41%; seven UC and five CD) Pediatric Weighted Crohn's Disease Activity Index (wPCDAI)/Pediatric Ulcerative Colitis Activity Index (PUCAI) patients after 4 and 12 months at the initiation of dual therapy. Clinical response based on wPCDAI/PUCAI was reported in 16 (55%; nine UC and seven CD) and 12 (41% seven UC and five CD) children after 4 and 12 months of follow‐up, respectively. The median fecal calprotectin decreased significantly from 1240 µg/g (53–10,100) to 160 µg/g (5–2500; p = 0.004) between baseline and Month 4 and from 749 at baseline (57–10,100) to 17 (5–3110; p = 0.12) over 12 months. Moreover, 34% (six UC and four CD) of patients achieved endoscopic remission.Conclusions: DBT seems to be an effective alternative therapeutic option for patients with moderate and severe IBD.

Background: Inflammatory bowel diseases in children are characterized by a wide variety of symptoms and often a severe clinical course. In the treatment, we aimed to induce and maintain remission. We focused on assessing the efficacy and safety of the concomitant use of two biologic therapies including: anti-TNF (infliximab, adalimumab) vedolizumab and ustekinumab in a refractory pediatric IBD cohort. Methods: Fourteen children (nine ulcerative colitis, one ulcerative colitis/IBD-unspecified, four Crohn’s disease) with a disease duration of 5.2 (8 months–14 years) years, initiated dual therapy at an age of 11.7 (3–17) years after failure of monotherapy with a biological drug. Five patients (36%) were treated with vedolizumab/adalimumab (VDZ + ADA), five (36%) with ustekinumab/adalimumab (UST + ADA), and three (21%) with infliximab/vedolizumab (IFX + VDZ). One patient (7%) was switched from a combination of vedolizumab and adalimumab to ustekinumab and adalimumab during follow-up. Results: A clinical improvement was obtained in ten children (73%; 5 UC, 1 UC/IBD-unspecified, 4 CD) on the PCDAI/PUCAI scale after 4 months of a second biological drug being added. The median fecal calprotectin decreased from 1610 µg/g (140–10,100) to 586 µg/g (5–3410; p = 0.028) between baseline and 4 months. Conclusions: Our clinical experience suggests that dual therapy may be an option for pediatric patients with moderate and severe courses of IBD with limited therapeutic options

Background: pediatric patients with inflammatory bowel diseases (IBD) who qualify for biological therapy represent a group of severely ill patients. They have never been successful with conventional medication. Biologic medications in monotherapy are frequently used in the disease course, however they result in a 1-year remission, which can be maintained in approximately 40% of IBD patients. Method: the present study aims to summarize the review of literature data on the use of therapy with a combination of two biological and small molecule drugs, anti-TNF (infliximab, adalimumab), vedolizumab and ustekinumab, as well as Janus kinase inhibitors (tofacitinib). The risks associated with the use of dual biological therapy and potential adverse effects are particularly important. The literature data was reviewed using the following terms: “use of combination biologic in paediatric IBD”, “combination biologics”, and “dual biologic for treatment of Inflammatory Bowel Disease”. Conclusion: the use of dual biological therapy is a new therapeutic option. In pediatric IBD, combining the different mechanisms of action of the two biological drugs seems to be safe and effective. Anti-TNF drugs with vedolizumab or ustekinumab may be a particularly beneficial combination. Nevertheless, the clarification and justification of potential advantages of combined biological therapies in further studies, such as randomized control trials, are needed.