Characteristics of biological therapy in pediatric patients with Crohn’s disease (original) (raw)
Related papers
Efficacy of Adalimumab in Moderate-to-Severe Pediatric Crohn's Disease
The American Journal of Gastroenterology, 2009
The use of tumor necrosis factor-alpha (TNF-) antagonists has changed the therapeutic strategy for Crohn ' s disease (CD). Adalimumab (ADA), a fully human anti-TNF-monoclonal antibody, is an effective therapy for patients with CD, both naive patients and those intolerant or refractory to Infl iximab (IFX), a chimeric anti-TNF-agent. However, the use of ADA is rarely reported in pediatric CD. We performed an open prospective evaluation of short-and long-term effi cacy and safety of ADA in children with moderate-to-severe CD.
Safety and Efficacy of Adalimumab in Pediatric Patients With Crohn Disease
Journal of Pediatric Gastroenterology & Nutrition, 2008
Objectives: Adalimumab has recently become available for adult patients with Crohn disease (CD) as a viable alternative tumor necrosis factor-a inhibitor to infliximab. To our knowledge, there have been no studies reviewing the use of adalimumab in pediatric patients with CD. Our aim was to examine the safety and efficacy of adalimumab therapy in pediatric patients with CD. Patients and Methods: We performed a retrospective chart review of 15 pediatric patients with CD who received adalimumab at a single institution between January 2003 and March 2007. All of the patients had a history of an attenuated response or anaphylaxis to infliximab. Each patient's chart was reviewed for age at diagnosis, sex, extent of disease, age at start of adalimumab therapy, course of therapy, side effects noted during therapy, concurrent medications, and response to adalimumab. Clinical response to adalimumab was classified as complete, partial, or no response based on the patients' ability to be weaned from steroids, increased or decreased need for steroids, or need for surgery during the course of treatment. This study was approved by the Cleveland Clinic Institutional Review Board. Results: Fifteen pediatric patients with CD received adalimumab for a 33-month period. Of those, 14 patients had adequate followup, and 1 patient was lost to follow-up. The mean age at initiation of therapy was 16.6 years (median 17.9 years, range 10.3-21.8 years, SD 3.1 years). The majority of patients received an 80-mg loading dose administered subcutaneously and 40-mg doses subsequently every 2 weeks. The median duration of therapy was 6.5 months (range 1-31 months). A total of 272 injections were given. Of the 14 patients with sufficient data for follow-up, 7 (50%) had a complete response, 2 (14%) had a partial response, and 5 (36%) had no response to adalimumab. Complete response was achieved after a median of 5 injections (range 3-11). Of the 14 patients with adequate follow-up, 5 had fistulizing disease; 3 of these maintained fistula closure, 1 had temporary closure, and 1 required surgery to assist with closure. Twenty-six adverse events occurred during therapy. Eight (57%) patients had at least 1 adverse effect. The most common events were abdominal pain and nausea. No serious adverse events were reported, no serious infections occurred, and no adverse events required discontinuation of adalimumab. Conclusions: Adalimumab was well tolerated in pediatric patients with CD. Complete or partial response was observed in 64% of patients. No serious adverse events occurred during therapy. Additional studies are needed to evaluate the efficacy and to determine optimal dosing of adalimumab in the pediatric population with CD.
Efficacy and Tolerance of Infliximab in Children and Adolescents with Crohn’s Disease
Inflammatory Bowel Diseases, 2004
Infliximab, a monoclonal antibody against tumor necrosis factor-alpha, has been shown to be effective for the treatment of refractory Crohn's disease in adult patients, but experience in pediatrics is limited. This retrospective study included 88 children and adolescents, 39 girls and 49 boys, with a median age of 14 years (range 3.3-17.9). Infliximab was indicated for active disease (66%) and/or fistulas (42%) that were refractory to corticosteroids (70%), and/or other immunosuppressive (82%) agents, and/or parenteral nutrition (20%). Patients received 1 to 17 infusions (median 4) of 5 mg/kg (range 3.8-7.3) of infliximab during a median time period of 4 months (1-17 months). Infusion reaction was noted in 13 patients (15%), with a total of 16 reactions in 450 infusions (4%). At Day 90 after the first infusion of infliximab, symptoms improved in 49% of patients, whereas 29% of patients were in remission and 13% of patients relapsed. From Day 0 to Day 90, Harvey-Bradshaw score decreased from 7.5 to 2.8 (P < 0.001), C-reactive protein from 36 to 16 mg/L (P < 0.01), and 1-hour erythrocyte sedimentation rate from 35 to 17 mm (P < 0.01). Dosage of corticosteroids decreased from to 0.59 to 0.17 mg/kg/d (P < 0.001); 53% of patients could be weaned of corticosteroids and 92% of parenteral nutrition. Treatment with infliximab is well tolerated and effective in most children and adolescents with Crohn's disease that is refractory to conventional immunosuppressive therapy. Nevertheless, long-term efficacy remains to be shown, and further studies are urgently needed to precisely determine the best modality of continuing treatment.
The Medical Management of Paediatric Crohn’s Disease: an ECCO-ESPGHAN Guideline Update
Journal of Crohn's and Colitis, 2020
ObjectiveWe aimed to provide an evidence-supported update of the ECCO-ESPGHAN guideline on the medical management of paediatric Crohn’s disease [CD].MethodsWe formed 10 working groups and formulated 17 PICO-structured clinical questions [Patients, Intervention, Comparator, and Outcome]. A systematic literature search from January 1, 1991 to March 19, 2019 was conducted by a medical librarian using MEDLINE, EMBASE, and Cochrane Central databases. A shortlist of 30 provisional statements were further refined during a consensus meeting in Barcelona in October 2019 and subjected to a vote. In total 22 statements reached ≥ 80% agreement and were retained.ResultsWe established that it was key to identify patients at high risk of a complicated disease course at the earliest opportunity, to reduce bowel damage. Patients with perianal disease, stricturing or penetrating behaviour, or severe growth retardation should be considered for up-front anti-tumour necrosis factor [TNF] agents in combi...
Scandinavian journal of gastroenterology, 2014
Pediatric Crohn's disease (CD) is often debilitating, with upper gastrointestinal (GI) involvement and complications over time. Treatment with tumor necrosis factor (TNF) blockers can induce and maintain remission. We wanted to evaluate the outcome of patients medically treated for CD to investigate whether clinical, endoscopic and biochemical factors at diagnosis are associated with the early initiation of treatment with the TNF blocker infliximab. Patients aged <18 years, diagnosed with CD were characterized according to the Porto criteria, with endoscopy, magnetic resonance imaging and biochemical tests before individual treatment. They were followed prospectively until a prescheduled examination within 2 years. Thirty-six pediatric patients were included, 18 (50%) received infliximab. Infliximab-treated patients had shorter disease duration, more upper GI involvement (p = 0.03) and higher median C-reactive protein (CRP) (28 vs. 7.5 mg/l, p = 0.02), erythrocyte sedimentati...
Long-term outcome of tumor necrosis factor alpha antagonist's treatment in pediatric Crohn's disease
Journal of Crohn's and Colitis, 2013
Background: Anti tumor necrosis factor alpha (TNFα) agents have become widely used in pediatric inflammatory bowel disease (IBD). So far, only few studies examined the long-term results of anti-TNFα treatment in children with IBD. Methods: The long-term outcome of pediatric patients with IBD was assessed retrospectively in a multicenter cohort of children treated with anti-TNFα beyond induction treatment. Short-and long-term response rates, predictors for loss of response, data on growth and laboratory parameters were assessed. Results: 120 patients [101 crohn's disease (CD), 19 ulcerative colitis (UC) or indeterminate colitis (IC)] received either infliximab or adalimumab. The mean age at initiation of anti-TNFα was 13.4 ± 3.9 years and the median duration of anti-TNFα treatment was 15 months (range: 2-90). Overall, 89% of the cohort experienced short-term response following induction. Response was associated with improvement in weight and BMI Z-scores (p b 0.001) but not with linear growth. Responders experienced a significant decrease in erythrocyte sedimentation rate (ESR) and C reactive protein (CRP) during treatment (p b 0.001). Albumin and hemoglobin both improved but only albumin increased significantly (p b 0.001).
Mucosal healing in pediatric Crohn’s disease after anti-TNF therapy
European Journal of Gastroenterology & Hepatology, 2014
Purpose The anti-tumor necrosis factor (TNF) agents infliximab (IFX) and adalimumab (ADA) have been recently introduced to treat severe inflammatory bowel disease (IBD) that is unresponsive to other drugs. Several studies have confirmed the safety and efficacy of these agents for adult IBD patients, whereas there is less data on pediatric IBD. Mucosal healing, associated with fewer complications and surgeries, is considered the goal of treatment by some authors. The objective of this study was to evaluate the safety and efficacy (in terms of endoscopic, clinical, and laboratoristic response) of IFX and ADA in a cohort of pediatric patients with Crohn's disease (CD).
2020
Ustekinumab is a monoclonal antibody that inhibits Background: interleukins 12 and 23. It is approved for treatment of Crohn's disease (CD) in adults; however, there is a paucity of data regarding its use in pediatric CD. We describe our experience using ustekinumab in anti-TNF refractory CD pediatric patients. We performed a retrospective chart review on pediatric patients Methods: with CD who were started on ustekinumab from January 2016 to November 2018. We collected patient's clinical history, previous treatment history, surgeries related to CD, disease severity, as measured by abbrPCDAI, and endoscopic severity as recorded by SES-CD before and after ustekinumab. We identified 10 patients with CD who were started on Results: ustekinumab due to non-response to currently approved agents. Seven patients needed augmented maintenance dosing every 4-6 weeks to achieve clinical response or remission. Six of these seven patients had therapeutic drug monitoring during the course of treatment, with five patients showing subtherapeutic drug levels of <4.5 μg/mL while on standard maintenance dosing every 8 weeks, and four patients showing therapeutic drug levels of >4.5 μg/mL on augmented dosing interval. The remaining three patients were on standard maintenance dosing for the duration of treatment. In this retrospective chart review, 7 out of 10 patients with Conclusion: anti-TNF refractory pediatric-onset CD required augmented maintenance doses of ustekinumab to achieve clinical response or remission. A prospective study is needed to define appropriate ustekinumab dosing and interval in management of pediatric CD.