Infliximab Optimization Based on Therapeutic Drug Monitoring in Pediatric Inflammatory Bowel Disease.

BACKGROUND: Infliximab (IFX) is an effective treatment for the management of moderate to severe inflammatory bowel disease (IBD). Low-serum IFX levels are associated with the development of antibodies to IFX (ATI), which subsequently associated with clinical relapse and increased morbidity. The primary purpose of this study is to examine the relation between dose and interval to IFX level. Secondary goal is to evaluate the relation between IFX level and ATI in a pediatric IBD population. METHODS: We performed a retrospective chart review of all children diagnosed with IBD and treated with IFX at a tertiary care pediatric IBD center. We performed our analysis based on prescribed dosing intervals and rounded dose up to 5 or 10 mg/kg as indicated in clinical practice. RESULTS: Our study included 278 samples from 129 children on IFX. ATI were detected in 37 samples (13.3%). Low IFX levels (<3 µg/mL) were detected in 37.2% of children receiving IFX. Samples with ATI present had significantly lower levels of IFX than samples in which ATI were not present. For the dose 5 mg/kg, Q6 dosing had significantly higher IFX levels than Q8 dosing (P = 0.009). Higher IFX levels were seen with interval shortening rather than dose escalation. CONCLUSIONS: We demonstrate that low IFX levels are associated with development of immunogenicity to IFX as measured by ATI. We demonstrate that interval shortening rather than dose escalation results in higher IFX levels. We suggest that given the high number of IFX levels below 3 µg/mL in patients, early IFX level evaluation or primary initiation of Q6 week dosing be considered.

Pilot Study Evaluating Efficacy of 2 Regimens for Hypovitaminosis D Repletion in Pediatric Inflammatory Bowel Disease.

OBJECTIVES: Vitamin D is critical for skeletal health; hypovitaminosis D is common in pediatric inflammatory bowel disease (IBD), yet optimal repletion therapy is not well studied. We aimed to conduct a pilot trial comparing the efficacy of 2 vitamin D regimens of weekly dosing for the repletion of hypovitaminosis D in pediatric IBD. METHODS: Subjects identified from our IBD clinic with 25-hydroxyvitamin D (25[OH]D) concentrations <30 ng/mL were randomized to 10,000 (n = 18) or 5000 (n = 14) IU of oral vitamin D3/10 kg body weight per week for 6 weeks. Serum 25(OH)D, Ca, and parathyroid hormone concentrations were measured at baseline, week 8, and week 12. RESULTS: In the higher dosing group, serum 25(OH)D increased from 23.7 ±â€Š8.5 ng/mL at baseline to 49.2 ±â€Š13.6 ng/mL at 8 weeks; P < 0.001. In the lower dosing group, serum 25(OH)D increased from 24.0 ±â€Š7.0 ng/mL at baseline to 41.5 ±â€Š9.6 ng/mL at 8 weeks; P < 0.001. At 12 weeks, serum 25(OH)D concentrations were 35.1 ±â€Š8.4 and 30.8 ±â€Š4.2 ng/mL for the higher and lower dose regimens, respectively. Mean serum Ca and parathyroid hormone concentrations did not significantly change during the study. No patient exhibited hypercalcemia, and no serious adverse events occurred. CONCLUSIONS: Both treatment arms were safe and effective at normalizing vitamin D nutriture in pediatric IBD. Although significant repletion of 25(OH)D concentration was achieved in both dosing groups at 8 weeks, this effect was lost by the 12-week follow-up. Maintenance vitamin D therapy following initial repletion is likely required to maintain long-term normalized vitamin D status.

A 14-year-old girl with recurrent vulvar abscess.

BACKGROUND: Inflammatory bowel disease is a relatively common condition that may present in a myriad of fashions, from the more frequently seen symptoms of diarrhea and abdominal pain to the less likely presentations with fistulas and abscesses. CASE: A 14-year-old female with a presumed diagnosis of a Bartholin's gland cyst was treated for over 1 year with both medical and surgical interventions without her symptoms ever completely resolving. It was later found that these recurring vulvar abscesses were a manifestation of Crohn's disease. CONCLUSION: While the patient's history and physical are both very important in determining cause for pathology, we must also realize the importance of re-examining and broadening our differential diagnosis when faced with a patient who has failed multiple avenues of care.

Vitamin D status and bone mineral density in African American children with Crohn disease.

BACKGROUND: Vitamin D deficiency and low bone mineral density (BMD) are complications of inflammatory bowel disease. Vitamin D deficiency is more prevalent among African Americans compared with whites. There are little data comparing differences in serum 25-hydroxyvitamin D (25OHD) concentrations and BMD between African American and white children with Crohn disease (CD). METHODS: We compared serum 25OHD concentrations of African American children with CD (n = 52) to white children with CD (n = 64) and healthy African American controls (n = 40). We also analyzed BMD using dual-energy x-ray absorptiometry results from our pediatric CD population. RESULTS: African American children with CD had lower serum 25OHD concentrations (16.1 [95% confidence interval, CI 14.5-17.9] ng/mL) than whites with CD (22.3 [95% CI 20.2-24.6] ng/mL; P < 0.001). African Americans with CD and controls exhibited similar serum 25OHD concentration (16.1 [95% CI 14.5-17.9] vs 16.3 [95% CI 14.4-18.4] ng/mL; NS). African Americans with CD exhibited no difference in serum 25OHD concentration when controlling for seasonality, disease severity, and surgical history, although serum 25OHD concentration was significantly decreased in overweight children (body mass index ≥85%, P = 0.003). Multiple regression analysis demonstrated that obese African American girls with CD had the lowest serum 25OHD concentrations (9.6 [95% CI 6.8-13.5] ng/mL). BMD was comparable between African American and white children with CD (z score -0.4 ± 0.9 vs -0.7 ± 1.2; NS). CONCLUSIONS: African American children with CD are more likely to have vitamin D deficiency compared with white children with CD, but have similar BMD. CD disease severity and history of surgery do not affect serum 25OHD concentrations among African American children with CD. African American children have low serum 25OHD concentrations, independent of CD, compared with white children. Future research should focus on how race affects vitamin D status and BMD in children with CD.