Background Adult studies suggest antibodies to infliximab (ATI) correlate with loss of response in inflammatory bowel disease but pediatric data are limited. Methods We conducted a cross-sectional study of trough infliximab levels and ATI in 134 pediatric and young adult patients receiving infliximab. At the time serum was obtained demographics, disease phenotype, duration of infliximab therapy, use of combination therapy (methotrexate or 6-mercaptopurine with infliximab), and surgery were recorded. Results Assays were performed on 134 subjects currently receiving infliximab (85 male; mean age, 17.3 ± 4.3 years; 114 Crohn’s disease and 20 ulcerative colitis). Infliximab use ranged from 12 days to 12 years: median 2.0 (interquartile range [1.1–4.3]) years. Twenty-seven of 134 (20%) patients had ATI ≥5 U/mL. Of patients with ATI ≥5 U/mL, 59% had infliximab levels <5 μg/mL, compared with 14% of patients with ATI <5 U/mL (P < 0.001). Ten (7%) patients (9 Crohn’s disease, 1 ulcerative colitis) underwent bowel resections after beginning infliximab infusions. Sixty percent who underwent surgery had ATI ≥12 U/mL; in contrast, only 8% of patients who did not undergo surgery had ATI ≥12 U/mL (P = 0.01). At the time of serum sampling, 50 (37%) patients were receiving combination therapy, compared with 84 (63%) on infliximab alone. Combination therapy at the time of serum sampling did not correlate with either increase infliximab levels or lower ATI compared with infliximab monotherapy. However, prior immunomodulator use was associated with lower antibody levels (P = 0.007). Conclusions ATI correlates with reduction in infliximab level and a higher risk of surgery in patients with inflammatory bowel disease.
AIMTo investigate of pediatric ulcerative colitis activity index (PUCAI) in ulcerative colitis correlate with mucosal inflammation and endoscopic assessment of disease activity (Mayo endoscopic score).METHODSWe reviewed charts from ulcerative colitis patients who had undergone both colonoscopy over 3 years. Clinical assessment of disease severity within 35 d (either before or after) the colonoscopy were included. Patients were excluded if they had significant therapeutic interventions (such as the start of corticosteroids or immunosuppressive agents) between the colonoscopy and the clinical assessment. Mayo endoscopic score of the rectum and sigmoid were done by two gastroenterologists. Inter-observer variability in Mayo score was assessed.RESULTSWe identified 99 patients (53% female, 74% pancolitis) that met inclusion criteria. The indications for colonoscopy included ongoing disease activity (62%), consideration of medication change (10%), assessment of medication efficacy (14%), and cancer screening (14%). Based on PUCAI scores, 33% of patients were in remission, 39% had mild disease, 23% had moderate disease, and 4% had severe disease. There was “moderate-substantial” agreement between the two reviewers in assessing rectal Mayo scores (kappa = 0.54, 95%CI: 0.41-0.68).CONCLUSIONEndoscopic disease severity (Mayo score) assessed by reviewing photographs of pediatric colonoscopy has moderate inter-rater reliability, and agreement was less robust in assessing patients with mild disease activity. Endoscopic disease severity generally correlates with clinical disease severity as measured by PUCAI score. However, children with inflamed colons can have significant variation in their reported clinical symptoms. Thus, assessment of both clinical symptoms and endoscopic disease severity may be required in future clinical studies.
BACKGROUND There is a small and poorly studied population of patients with mild and limited Crohn’s disease (CD), who either spontaneously enter remission and can discontinue therapy, or be maintained on milder anti-inflammatory treatment. AIM To identify a group of children with mild CD who were not escalated to immunomodulators (azathioprine, mercaptopurine, or methotrexate) or biologics (infliximab or adalimumab) within the first two years after their Crohn’s diagnosis and outline the natural history and phenotypic features of these patients. METHODS In a retrospective chart review of the inflammatory bowel disease database at Boston Children’s Hospital we reviewed all the mild CD patient’s clinic visits, laboratory studies, and procedures for the duration of time they were followed at the center. Patients were included if they had clear diagnosis of Crohn’s disease, and they were not escalated to immunosuppressive therapies for at least 2 years after the date of diagnosis. These mild CD patients were compared to controls diagnosed at a similar time, that were treated with immunomodulators or biologics. Data that was abstracted included: Age at diagnosis, sex, disease location utilizing the Paris classification, medical treatment, surgical treatment, endoscopic findings, histology, and hospitalizations. We also analyzed differences in the phenotypic features between those with mild CD and those with moderate to severe disease. RESULTS Out of 1205 patients with CD diagnosed between 1990 and 2013, we identified 29 patients that met the inclusion criteria, and they were matched with 58 controls. There were no significant differences between the disease behaviors at presentation, with approximately 90% of patients in each group having inflammatory disease. However, patients with mild disease were more likely to have disease limited to the colon (31% vs 12%, P = 0.03). In contrast, patients with moderate to severe disease (aka control group) were more likely to have ileocolonic disease (70% vs 45% in the mild group, P = 0.02). Of the 29 patients, only 8 required medication escalation to immunomodulators during the period of follow-up. The primary indication for escalation to immune suppressive therapies was corticosteroid dependence. We also found that patients treated without immunomodulators or biologics for mild CD continue to exhibit histologic intestinal inflammation. Of the 29 patients, three developed significant complications of ileal disease, though only one required surgical intervention during the period of follow-up. CONCLUSION We identified a cohort of children with mild CD, who were able to avoid the institution of immune suppressive therapies for several years, and generally had good outcomes during the period of follow-up. While a subset of these patients will ev...
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