Refractory chronic inflammatory bowel disease in childhood and adolescence

BACKGROUND: The incidence of inflammatory bowel disease among children and adolescents in Europe is approximately 10 per 100 000 per year. Refractory disease courses are clinically significant and associated with delayed growth and development, recurrent hospitalizations, and the need for surgery. 10-40% of patients have a primary nonresponse to anti-TNFα therapies, and a further 5-20% per year have secondary treatment failure, defined as loss of response after an initial response while on maintenance treatment. The aim of this review is to summarize current treatment options for primary non-response or secondary treatment failure. METHOD: This narrative review is based on current guidelines and pertinent publications retrieved by a selective search in the PubMed, Ovid MEDLINE, and Cochrane databases. RESULTS: Before switching to another drug class, a standardized reevaluation is essential, incorporating clinical findings, biomarkers, endoscopy and/or imaging, and therapeutic drug monitoring. Following failure of anti-TNFα therapy, ustekinumab (approved for Crohn’s disease for patients ≥ 2 years of age) and vedolizumab (currently exclusively off-label) represent the best-established options in pediatric care. Reported clinical remission rates are 51% at week 52 for ustekinumab and 32% (Crohn's disease) and 42% (ulcerative colitis) at week 14 for vedolizumab. For IL-23p19 antibodies, Janus kinase inhibitors, and sphingosine-1-phosphate receptor modulators, the available evidence is still derived predominantly from adult studies, with very limited data from pediatric practice. Surgery remains an important option in complicated disease courses. CONCLUSION: Given the limited pediatric evidence and the frequent off-label use of newer agents, there is a need for prospective studies, registry data, and structured treatment algorithms to more reliably define the efficacy and long-term safety of treatments for pediatric chronic inflammatory bowel disease. In our view, children and adolescents with refractory inflammatory bowel disease should be managed by an interdisciplinary team in a center with the requisite experience.