Causes of Treatment Failure in Children With Inflammatory Bowel Disease Treated With Infliximab: A Pharmacokinetic Study
| Autor: | Matteo Bramuzzo, Gabriele Stocco, Eva Cuzzoni, Tania Silvestri, Oriano Radillo, Patrizia Alvisi, Alessandro Ventura, Giuliana Decorti, Stefano Martelossi, Martina Pozzi Mucelli, Adriana Cifù, Martina Fabris, Diego Favretto, Doriana Lacorte, Andrea Taddio, Marianna Lucafò, Samuele Naviglio |
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| Přispěvatelé: | Naviglio, Samuele, Lacorte, Doriana, Lucafò, Marianna, Cifù, Adriana, Favretto, Diego, Cuzzoni, Eva, Silvestri, Tania, Pozzi Mucelli, Martina, Radillo, Oriano, Decorti, Giuliana, Fabris, Martina, Bramuzzo, Matteo, Taddio, Andrea, Stocco, Gabriele, Alvisi, Patrizia, Ventura, Alessandro, Martelossi, Stefano |
| Rok vydání: | 2019 |
| Předmět: |
Male
Drug medicine.medical_specialty Necrosis Adolescent media_common.quotation_subject Enzyme-Linked Immunosorbent Assay Pediatrics Severity of Illness Index Gastroenterology Inflammatory bowel disease 03 medical and health sciences 0302 clinical medicine Crohn Disease Gastrointestinal Agents Pharmacokinetics Perinatology and Child Health 030225 pediatrics Internal medicine Severity of illness medicine Humans Prospective Studies Treatment Failure Colitis Child Prospective cohort study media_common Pediatric Dose-Response Relationship Drug business.industry Antibodies Monoclonal medicine.disease Infliximab digestive system diseases Pediatrics Perinatology and Child Health Colitis Ulcerative Female 030211 gastroenterology & hepatology Drug Monitoring medicine.symptom business medicine.drug |
| Zdroj: | Journal of Pediatric Gastroenterology & Nutrition. 68:37-44 |
| ISSN: | 1536-4801 0277-2116 |
| DOI: | 10.1097/mpg.0000000000002112 |
| Popis: | Objectives: Anti-tumor necrosis factor antibodies have led to a revolution in the treatment of inflammatory bowel diseases (IBD); however, a sizable proportion of patients does not respond to therapy. There is increasing evidence suggesting that treatment failure may be classified as mechanistic (pharmacodynamic), pharmacokinetic, or immune-mediated. Data regarding the contribution of these factors in children with IBD treated with infliximab (IFX) are still incomplete. The aim was to assess the causes of treatment failure in a prospective cohort of pediatric patients treated with IFX. Methods: This observational study considered 49 pediatric (median age 14.4) IBD patients (34 Crohn disease, 15 ulcerative colitis) treated with IFX. Serum samples were collected at 6, 14, 22 and 54 weeks, before IFX infusions. IFX and anti-infliximab antibodies (AIA) were measured using enzyme linked immunosorbent assays. Disease activity was determined by Pediatric Crohn's Disease Activity Index or Pediatric Ulcerative Colitis Activity Index. Results: Clinical remission, defined as a clinical score 3.11 μg/mL emerged as the strongest predictor of sustained clinical remission. AIA concentrations were correlated inversely with IFX concentrations and directly with adverse reactions. Conclusions: Most cases of therapeutic failure were associated with low serum drug levels. IFX trough levels at the end of induction are associated with sustained long-term response. |
| Databáze: | OpenAIRE |
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