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Refractory Chronic Inflammatory Bowel Disease in Childhood and Adolescence: Options in Primary Non-Response or
Insights
For pediatric inflammatory bowel disease patients unresponsive to anti-TNFα therapies, ustekinumab and vedolizumab are established options. Further research is needed to define long-term efficacy and safety of newer agents.
Area of Science:
- Pediatric Gastroenterology
- Immunology
- Pharmacology
Background:
- Inflammatory bowel disease (IBD) affects approximately 10 per 100,000 children and adolescents annually in Europe.
- Refractory IBD courses in pediatric patients lead to significant complications, including growth delay, frequent hospitalizations, and surgical interventions.
- Primary non-response to anti-tumor necrosis factor-alpha (anti-TNFα) therapies affects 10-40% of patients, with an additional 5-20% experiencing secondary treatment failure annually.
Purpose of the Study:
- To review current treatment strategies for pediatric patients with primary non-response or secondary treatment failure to anti-TNFα therapies.
- To summarize the efficacy and safety data for established and emerging biologic and targeted therapies in pediatric IBD.
Main Methods:
- A narrative review of current guidelines and relevant publications.
- Literature search conducted in PubMed, Ovid MEDLINE, and Cochrane databases.
Main Results:
- Standardized reevaluation, including clinical assessment, biomarkers, and imaging, is crucial before switching therapies.
- Ustekinumab and vedolizumab are the most established options for pediatric IBD after anti-TNFα failure, with reported remission rates of 51% (ustekinumab) and 32-42% (vedolizumab).
- Evidence for newer agents like IL-23p19 inhibitors and JAK inhibitors in pediatric populations is limited, primarily derived from adult studies. Surgery remains vital for complicated cases.
Conclusions:
- Limited pediatric data and off-label use of newer agents necessitate prospective studies and registries to establish efficacy and long-term safety.
- Management of refractory pediatric IBD requires an interdisciplinary team approach at experienced centers.
- Development of structured treatment algorithms is essential for optimizing care in pediatric chronic IBD.
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.
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