The Continental Divide: Anti-TNF Use in Pediatric IBD Is Different in North America Compared to Other Parts of the World.

Background and Aims: Use of anti-TNF therapies varies internationally. As an initiative of the international Pediatric IBD Network (PIBDNet), we compared global pediatric IBD anti-TNF practice patterns. Methods: Physicians were surveyed about anti-TNF use in Crohn's disease (CD) and ulcerative colitis (UC). Chi-squared, independent samples Mann-Whitney U, or related samples Wilcoxon signed rank tests were used to compare groups. Results: 344 physicians treating pediatric IBD responded from 43 countries (54% North America, 29% Europe, 6% Oceania, 6% Asia, 3% Africa, and 2% South America). Respondents treated a median 40 IBD patients. CD was more commonly treated with anti-TNF than UC (40% vs. 10%, p<0.001). North Americans more often used anti-TNF (median 50% vs. 30%, p<0.001) and before immunomodulator (80% vs. 35% CD, p<0.001; 76% vs. 43% steroid-dependent UC, p<0.001). Anti-TNF monotherapy was more common in North America. Anti-TNF in combination with methotrexate, instead of thiopurine, characterized North American practices. North Americans more often continued immunomodulator indefinitely and less often adhered to standard infliximab induction dosing. Access limitations were more common outside North America and Europe for both CD (67% vs. 31%, p<0.001) and UC (62% vs. 33%, p<0.001). Conclusions: Anti-TNF use in North America varies significantly from elsewhere.

Safety of Adalimumab in Pediatric Patients with Polyarticular Juvenile Idiopathic Arthritis, Enthesitis-Related Arthritis, Psoriasis, and Crohn's Disease.

OBJECTIVE: To evaluate the safety of adalimumab in pediatric patients who participated in clinical trials of juvenile idiopathic arthritis (polyarticular juvenile idiopathic arthritis and pediatric enthesitis-related arthritis), psoriasis, and Crohn's disease. STUDY DESIGN: This analysis included data from 7 global, randomized, and open-label AbbVie-sponsored clinical trials of adalimumab and their open-label extensions conducted between September 2002 and December 31, 2015 (cutoff date for ongoing studies). Patients who received ≥1 dose of adalimumab subcutaneously were included. Adverse events that occurred after the first dose of adalimumab and up to 70 days (5 half-lives) after the last dose were reported and events per 100 patient-years were calculated. RESULTS: The analysis included 577 pediatric patients, representing 1440.7 patient-years of adalimumab exposure. Across indications, the most commonly reported adverse events (events/100 patient-years) were upper respiratory tract infections (24.3), nasopharyngitis (17.3), and headache (19.9). Serious infections (4.0 events/100 patient-years) were the most frequent serious adverse events across indications; the most commonly reported was pneumonia (0.6 events/100 patient-years). Serious infection rates were 2.7, 0.8, and 6.6 events/100 patient-years in patients with juvenile idiopathic arthritis, psoriasis, and Crohn's disease, respectively. No events of malignancies were reported. One death (accidental fall) occurred in a patient with psoriasis. CONCLUSIONS: The safety profile of adalimumab in pediatric patients with polyarticular juvenile idiopathic arthritis, enthesitis-related arthritis, psoriasis, and Crohn's disease was generally similar across indications; no new safety signals were identified in the treatment of pediatric patients with adalimumab. TRIAL REGISTRATION: Clinicaltrials.gov: NCT00048542, NCT00775437, NCT00690573, NCT01166282, NCT01251614, NCT00409682, and NCT00686374.

Prevalence of Pediatric Functional Gastrointestinal Disorders Utilizing the Rome IV Criteria.

OBJECTIVE: To assess the prevalence of functional gastrointestinal (GI) disorders in children 0-18 years old according to the newly established Rome IV diagnostic criteria as reported by parents in a representative community sample. STUDY DESIGN: A cross-sectional study in which mothers (n = 1255) of children aged 0-18 years old in the US were recruited to complete an online survey about their child's GI symptoms, quality of life (QoL), and other health conditions. RESULTS: Based on the Rome IV criteria, 24.7% of infants and toddlers aged 0-3 years and 25.0% of children and adolescents aged 4-18 years fulfilled symptom-based criteria for a functional GI disorder. The most common functional GI disorders were infant regurgitation among infants (24.1%) and functional constipation among both toddlers (18.5%) and children and adolescents (14.1%). QoL was diminished in pediatric patients with functional GI disorders (median = 71.69 vs median = 87.60; z = -11.41; P < .001). Children were more likely to qualify for a functional GI disorder if their parent qualified for a functional GI disorder (35.4% vs 23.0%; P < .001). CONCLUSIONS: Based on Rome IV criteria, functional GI disorders are common in pediatric populations of all ages and are associated with decreased QoL.

Clinical Presentation and Five-Year Therapeutic Management of Very Early-Onset Inflammatory Bowel Disease in a Large North American Cohort.

OBJECTIVE: To evaluate the presentation, therapeutic management, and long-term outcome of children with very early-onset (VEO) (≤ 5 years of age) inflammatory bowel disease (IBD). STUDY DESIGN: Data were obtained from an inception cohort of 1928 children with IBD enrolled in a prospective observational registry at multiple centers in North America. RESULTS: One hundred twelve children were ≤ 5 years of age with no child enrolled at <1 year of age. Of those, 42.9% had Crohn's disease (CD), 46.4% ulcerative colitis (UC), and 10.7% had IBD-unclassified. Among the children with CD, children 1-5 years of age had more isolated colonic disease (39.6%) compared with 6- to 10-year-olds (25.3%, P = .04), and 11- to 16-year-olds (22.3%, P < .01). The change from a presenting colon-only phenotype to ileocolonic began at 6-10 years. Children 1-5 years of age with CD had milder disease activity (45.8%) at diagnosis compared with the oldest group (28%, P = .01). Five years postdiagnosis, there was no difference in disease activity among the 3 groups. However, compared with the oldest group, a greater proportion of 1- to 5-year-olds with CD were receiving corticosteroids (P < .01) and methotrexate (P < .01), and a greater proportion of 1- to 5-year-olds with UC were receiving mesalamine (P < .0001) and thiopurine immunomodulators (P < .0002). CONCLUSIONS: Children with VEO-CD are more likely to have mild disease at diagnosis and present with a colonic phenotype with change to an ileocolonic phenotype noted at 6-10 years of age. Five years after diagnosis, children with VEO-CD and VEO-UC are more likely to have been administered corticosteroids and immunomodulators despite similar disease activity in all age groups. This may suggest development of a more aggressive disease phenotype over time.

Body mass index in children with newly diagnosed inflammatory bowel disease: observations from two multicenter North American inception cohorts.

OBJECTIVE: To conduct a systematic review of children with newly diagnosed inflammatory bowel disease (IBD) from 2 prospective inception cohorts to examine body mass index (BMI) status at presentation. STUDY DESIGN: Clinical, demographic, and BMI data were obtained from 783 patients with newly diagnosed IBD. National Health and Nutrition Examination Survey data for 2748 healthy children were used as a control. RESULTS: Most children with Crohn's disease and ulcerative colitis had a BMI in the normative range (5%-84%). Low BMI (<5%) was seen in 22% to 24% of children with Crohn's disease and 7% to 9% of children with ulcerative colitis. Ten percent of children with Crohn's disease and 20% to 30% of children with ulcerative colitis had a BMI at diagnosis consistent with overweight or risk for overweight. CONCLUSION: Children with IBD are affected by current population trends toward overweight. A significant subgroup of children with newly diagnosed IBD has a BMI categorized as overweight or at risk for overweight. Clinicians should be aware of possible IBD diagnosis in the presence increased BMI.

Are activated T cells regulators of bone metabolism in children with Crohn disease?

OBJECTIVES: To test the hypothesis that circulating activated T cells may release cytokines that decrease bone turnover in children with Crohn disease. STUDY DESIGN: Newly diagnosed Crohn disease and healthy controls of similar age were compared for bone age, bone mineral content and density, markers of bone remodeling, and serum concentration and in vitro T-cell production of receptor activator of nuclear factor kappaB ligand (RANKL), interferon (INF)-gamma, and osteoprotegerin (OPG). RESULTS: Newly diagnosed children with Crohn disease (n=23) had similar bone mineral density (BMD) z-scores and body mass index as the controls (n=40). Biochemical markers of bone remodeling indicated a state of low bone turnover in the Crohn disease patients compared with controls. Serum OPG (pmol/L; mean+/-SD, median) was higher (4.24+/-1.74, 3.98 vs 3.38+/-0.83, 3.41; P<.05), and serum RANKL (pmol/L) was lower in the Crohn disease patients (0.50+/-0.86, 0.28 vs 1.02+/-1.63, 0.49; P<.01), consistent with decreased bone resorption. Activated T cells from Crohn disease patients produced a higher concentration of INF-gamma (ng/microg protein) than those from controls (20.03+/-26.39, 8.70 vs 9.76+/-14.10, 6.17; P<.05). CONCLUSIONS: The newly diagnosed children with Crohn disease exhibited reduced bone remodeling, possibly due to T-cell INF-gamma and OPG.