Pediatric ulcerative colitis: current treatment approaches including role of infliximab

Division of Pediatric, Gastroenterology and Nutrition, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
Biologics: Targets & Therapy 06/2012; 6:125-34. DOI: 10.2147/BTT.S31833
Source: PubMed

ABSTRACT Ulcerative colitis is a chronic inflammatory bowel disease that can lead to derangements in the growth, nutritional status, and psychosocial development of affected children. There are several medical options for the induction and maintenance of disease remission, but the benefits of these medications need to be carefully weighed against the risks, especially in the pediatric population. As the etiology of the disease has become increasingly understood, newer therapeutic alternatives have arisen in the form of biologic therapies, which are monoclonal antibodies targeted to a specific protein or receptor. This review will discuss the classical treatments for children with ulcerative colitis, including 5-aminosalicylates, corticosteroids, thiopurine immunomodulators, and calcineurin inhibitors, with a particular focus on the newer class of anti-tumor necrosis factor-α agents.

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    ABSTRACT: To assess infliximab pharmacokinetics in pediatric ulcerative colitis (UC). This phase 3, randomized, open-label multicenter study enrolled 60 children (6-17 yr) with moderate-to-severely active UC (Mayo score, 6-12; endoscopic subscore, ≥2), despite conventional therapy. Patients received infliximab 5-mg/kg induction infusions at weeks 0, 2, and 6. Week 8 clinical responders (n = 45) were randomized to infliximab 5 mg/kg given every (q) 8 weeks through week 46 or every 12 weeks (q12w) through week 42. Patients losing response during maintenance infliximab were eligible to increase the dose (5→10 mg/kg) and/or shorten the dosing interval (q12w→q8w). Blood samples were collected for infliximab concentration and pharmacokinetic determinations. Infliximab pharmacokinetics was not influenced by age (6-11 yr versus 12-17 yr), baseline immunomodulator use, or the extent of UC. At week 8, higher serum infliximab concentrations (≥41.1 μg/mL) were associated with greater proportions of patients achieving efficacy endpoints (clinical response, 92.9%; mucosal healing, 92.9%; and clinical remission, 64.3%) versus those with lower serum concentrations (<18.1 μg/mL; 53.9%, 53.9%, and 30.8%, respectively). At week 30, higher median trough serum infliximab concentrations were observed with infliximab 5 mg/kg q8w (1.9 μg/mL) versus q12w (0.8 μg/mL) and with infliximab 10 mg/kg (2.9 μg/mL) versus 5 mg/kg (1.1 μg/mL) among patients who are regimen adjusted. Infliximab pharmacokinetics/exposure-response relationship in patients with UC aged 6 to 17 years were generally comparable with those observed in reference adult UC populations, supporting using infliximab 5 mg/kg at weeks 0, 2, and 6 followed by maintenance dosing with 5 mg/kg q8w in these patients. A positive relationship was noted between serum infliximab level and clinical effect following induction therapy similar to adults.
    Inflammatory Bowel Diseases 11/2013; 19(13). DOI:10.1097/01.MIB.0000435438.84365.f7 · 5.48 Impact Factor
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    ABSTRACT: Childhood obesity is an increasing problem in affluent societies throughout the world. We sought to identify the impact of obesity on the outcome of inflammatory bowel disease (IBD) and determine differences (if any) between ulcerative colitis (UC) and Crohn's disease (CD). The 2009 Kids' Inpatient Database was explored for all children (≤20years) admitted with IBD. ICD-9 codes were used to identify obesity and complications, including hemorrhage, perforation, and complex fistulas. Logistic regression analysis accounting for demographics, underlying disease, surgical procedures, and obesity was performed to identify factors associated with complication development. Data are expressed as odds ratios (OR) and a 95% confidence interval (CI). A P value of 0.05 was regarded as significant. From 12,465 admissions, 164 children were obese (1.3%), with no difference between CD and UC (1.3% vs. 1.4%; P=0.60). Girls had a two-fold increase in obesity (OR: 2.06, CI: 1.48-2.86; P<0.01). Obesity had no effect on elective/emergent admission rate (OR: 0.85, CI: 0.54-1.35; P=0.49), perforation (OR: 0.76, CI: 0.13-4.46; P=0.76), hemorrhage (OR: 0.64,CI: 0.34-1.21; P=0.17), complex fistula (OR: 1.19, CI: 0.45-3.17; P=0.72), or requirement for surgery (OR: 0.80, CI: 0.48-1.31; P=0.37). While the overall clinical morbidity rate was 10.7%, obesity was not associated with the development of overall complications (OR 1.20, CI: 0.75-1.93; P=0.45) or length of stay (6.36 vs. 6.10days; P=0.61). Obesity increased the rate of central venous catheter (CVC) infections (OR: 10.98, CI: 2.50-48.20; P<0.01). Obesity was more prevalent in girls with IBD. While obesity did not alter disease severity, rate of surgical intervention, or hospital length of stay, it was associated with higher CVC infections.
    Journal of Pediatric Surgery 02/2014; 49(2):265-8. DOI:10.1016/j.jpedsurg.2013.11.033 · 1.31 Impact Factor
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    ABSTRACT: Background. Restorative proctocolectomy with ileal-pouch anal anastomosis (IPAA) has some peculiarities in paediatric ulcerative colitis (UC). Aims. The primary aim was to compare the bowel function of patients undergoing IPAA between those operated on in childhood and adulthood. The secondary aim was to compare the quality of life (QoL) and outcomes for children between medical and surgical therapies. Method. Children undergoing IPAA were compared with adult patients undergoing IPAA between 2007 and 2012. Function was assessed 1 year after ileostomy closure. Function and QoL of medically managed paediatric patients were compared with their surgical counterparts. Results. Twelve paediatric IPAA patients were compared with 24 adult ones. Acute presentation was common in the former, usually after failed biological treatment. Recurrent pouchitis was more frequent in children. Younger patients exhibited a trend toward better discrimination and continence. QoL was excellent in both groups. Twelve medically treated children were enrolled for secondary aim. Functioning was similar in IPAA- and medically managed children, but the former had a better QoL, confirmed by parents' perception. Conclusions. Similar function is achieved by IPAA in childhood or adulthood. IPAA may offer a better QoL compared to prolonged medical management. The beneficial effects of IPAA experienced by children were similarly observed by their parents.
    Gastroenterology Research and Practice 03/2014; 2014:340341. DOI:10.1155/2014/340341 · 1.50 Impact Factor

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