High Body Mass Index and Response to Anti-Tumor Necrosis Factor Therapy in Pediatric Crohn's Disease.

INTRODUCTION: Obesity is common among patients with pediatric Crohn's disease (PCD). Some adult studies suggest obese patients respond less well to anti-tumor necrosis factor (TNF) treatment. This study sought compares anti-TNF response and anti-TNF levels between pediatric patients with normal and high body mass index (BMI). METHODS: The COMBINE trial compared anti-TNF monotherapy with combination therapy with methotrexate in patients with PCD. In this secondary analysis, a comparison of time-to-treatment failure among patients with normal BMI vs BMI Z -score >1, adjusting for prescribed anti-TNF (infliximab [IFX] or adalimumab [ADA]), trial treatment assignment (combination vs monotherapy), and relevant covariates. Median anti-TNF levels across BMI category was also examined. RESULTS: Of 224 participants (162 IFX initiators and 62 ADA initiators), 111 (81%) had a normal BMI and 43 (19%) had a high BMI. High BMI was associated with treatment failure among ADA initiators (7/10 [70%] vs 12/52 [23%], hazard ratio 0.29, P = 0.007) but not IFX initiators. In addition, ADA-treated patients with a high BMI had lower ADA levels compared with those with normal BMI (median 5.8 vs 12.8 µg/mL, P = 0.02). IFX trough levels did not differ between BMI groups. DISCUSSION: Overweight and obese patients with PCD are more likely to experience ADA treatment failure than those with normal BMI. Higher BMI was associated with lower drug trough levels. Standard ADA dosing may be insufficient for overweight children with PCD. Among IFX initiators, there was no observed difference in clinical outcomes or drug levels, perhaps due to weight-based dosing and/or greater use of proactive drug monitoring.

Comparative Effectiveness of Anti-TNF in Combination With Low-Dose Methotrexate vs Anti-TNF Monotherapy in Pediatric Crohn's Disease: A Pragmatic Randomized Trial.

BACKGROUND & AIMS: Tumor necrosis factor inhibitors, including infliximab and adalimumab, are a mainstay of pediatric Crohn's disease therapy; however, nonresponse and loss of response are common. As combination therapy with methotrexate may improve response, we performed a multicenter, randomized, double-blind, placebo-controlled pragmatic trial to compare tumor necrosis factor inhibitors with oral methotrexate to tumor necrosis factor inhibitor monotherapy. METHODS: Patients with pediatric Crohn's disease initiating infliximab or adalimumab were randomized in 1:1 allocation to methotrexate or placebo and followed for 12-36 months. The primary outcome was a composite indicator of treatment failure. Secondary outcomes included anti-drug antibodies and patient-reported outcomes of pain interference and fatigue. Adverse events (AEs) and serious AEs (SAEs) were collected. RESULTS: Of 297 participants (mean age, 13.9 years, 35% were female), 156 were assigned to methotrexate (110 infliximab initiators and 46 adalimumab initiators) and 141 to placebo (102 infliximab initiators and 39 adalimumab initiators). In the overall population, time to treatment failure did not differ by study arm (hazard ratio, 0.69; 95% CI, 0.45-1.05). Among infliximab initiators, there were no differences between combination and monotherapy (hazard ratio, 0.93; 95% CI, 0.55-1.56). Among adalimumab initiators, combination therapy was associated with longer time to treatment failure (hazard ratio, 0.40; 95% CI, 0.19-0.81). A trend toward lower anti-drug antibody development in the combination therapy arm was not significant (infliximab: odds ratio, 0.72; 95% CI, 0.49-1.07; adalimumab: odds ratio, 0.71; 95% CI, 0.24-2.07). No differences in patient-reported outcomes were observed. Combination therapy resulted in more AEs but fewer SAEs. CONCLUSIONS: Among adalimumab but not infliximab initiators, patients with pediatric Crohn's disease treated with methotrexate combination therapy experienced a 2-fold reduction in treatment failure with a tolerable safety profile. CLINICALTRIALS: gov, Number: NCT02772965.

Can colonic manometry studies be done on the day of colonic motility catheter placement?

BACKGROUND AND AIMS: Colonic manometry has been used to assess colonic neuromuscular integrity in pediatric patients with severe constipation unresponsive to standard medical therapy and to tailor their treatment plans. There are presently no available standard protocols for conducting colonic manometry studies. The aim of the present study was to determine whether colonic manometry studies can be conducted on the same day the colonic motility catheters are placed and to compare the effects of inhaled sevoflurane versus intravenous propofol, used during catheter placement, on colonic motility. METHODS: Twenty patients, randomized to receive sevoflurane or propofol during catheter placement, underwent colonic manometry on the day of catheter placement as well as the day after. The total motility index (MI), change in MI in response to a meal and bisacodyl, and presence of high-amplitude propagating contractions were compared between the 2 studies for each patient. RESULTS: Ten patients were allocated to sevoflurane and 10 patients to propofol. A total of 8 (80%) patients in the sevoflurane group and 9 (90%) patients in the propofol group had no differences in their studies between days 1 and 2 when the tracings were interpreted manually for gross evidence of high-amplitude propagating contractions and gastrocolonic reflex. Similarly, there was no change in the total MI between studies done on days 1 and 2 in either sevoflurane (978 ± 232 vs 978 ± 184; P = 0.99) or propofol (968 ± 200 vs 1078 ± 227; P = 0.29) group. When comparing change in MI in response to a meal or bisacodyl between the 2 days, there was no statistical difference noted in either group. CONCLUSIONS: Colonic manometry studies can be conducted as early as 4 hours following catheter placement with either propofol or sevoflurane used for anesthesia.

Significance of esophageal Crohn disease in children.

BACKGROUND AND AIM: Esophageal Crohn disease (ECD) is more common than it was originally thought to be. Only limited information, however, is available regarding its significance and effect on clinical course in the pediatric population. The aim of the study was to determine the prevalence of ECD in our patient population and compare clinical features and severity of disease among patients with ECD and nonesophageal Crohn disease (NECD). PATIENTS AND METHODS: Medical records of all patients with ECD diagnosed during a 12-year period based on specific endoscopic and histological criteria were reviewed and compared with a random group of patients with NECD. RESULTS: During the study period, 81 (20%) patients with ECD were identified. Mean age at diagnosis was 12 (range 4-19 years) with a male predominance of 63%. Only 29 (36%) patients had symptoms suggestive of upper gastrointestinal involvement. Endoscopic ulcers were present in 45 (56%) of patients with ECD, whereas noncaseating granulomas were found in 10 (12%) of those patients. The majority (89%) of these patients had concomitant gastric and/or duodenal involvement. When compared with 160 random patients with NECD, patients with ECD had higher mean Pediatric Crohn Disease Activity Index scores (40.2 vs 23.9; P < 0.001), more penetrating-type disease (12% vs 2%; P = 0.001), and a greater frequency of perianal involvement (51% vs 33%; P = 0.005) at diagnosis. No differences, however, were noted between the 2 groups in terms of need for surgical resection throughout duration of follow-up. CONCLUSIONS: Patients with ECD may represent a phenotype of Crohn disease with a more severe presentation. Patients with perianal disease at the time of initial physical examination should be considered for an upper endoscopy in addition to the colonoscopy to exclude esophageal involvement despite the absence of specific upper gastrointestinal symptoms. These observations should foster additional investigation into ECD phenotype to determine appropriate treatment and prognosis.

Incidental gastric eosinophils in patients with eosinophilic esophagitis: do they matter?

BACKGROUND AND AIM: Some patients with eosinophilic esophagitis (EE) (>15 eosinophils/high-power field on esophageal mucosal biopsies and lack of response to acid suppression and/or normal pH probe study) demonstrate incidental eosinophilic inflammation of the gastric mucosa. It is unclear whether patients with EE and normal gastric biopsies (EE-N) are phenotypically different from patients with EE and gastric mucosal abnormalities (EE-A) (ie, >10 eos/hpf on gastric biopsies). The aim of the study was to compare the clinical features and response to therapy among patients with EE-N and EE-A. PATIENTS AND METHODS: Medical records of all of the EE-A and a random group of patients with EE-N diagnosed during an 8-year period were reviewed. A subgroup analysis of patients treated with swallowed fluticasone with a repeat esophagogastroduodenoscopy within 6 months of starting therapy was also performed. RESULTS: During the study period, 41 patients had EE-A. When compared to 50 random patients with EE-N, no clinical differences were noted, including sex, age, presenting symptoms, esophageal histology, and atopy history. Eleven (27%) of the 41 EE-A and 14 (28%) of the 50 EE-N patients were treated with swallowed fluticasone, and the response was similar among the groups. The mean esophageal eosinophils/high-power field among the EE-A group dropped from 47 to 8 compared with a 46 to 7 drop among the EE-N group treated with fluticasone therapy (P = 0.91). In 9 (82%) of the 11 patients with EE-A treated with fluticasone, there was resolution (7 of 9) or significant improvement (2 of 9) of gastric eosinophilia. CONCLUSIONS: Patients with EE-A and EE-N have similar clinical presentations. Incidental gastric inflammation does not predict a worse response of esophageal inflammation to fluticasone and should not exclude its use in patients with EE-A. In fact, gastric inflammation responded to swallowed fluticasone in the majority of patients with EE-A. This observation should foster further investigation into pathogenesis of EE and presumed esophagogastric inflammatory axis.

Functional gastrointestinal disorders: past and present.

BACKGROUND: Chronic abdominal pain is a common complaint in childhood and adolescence. Despite decades of clinical observations and research, it still poses a challenge to pediatric health care professionals. The aim of this review is to highlight the epidemiology of pediatric chronic abdominal pain and to describe the pathogenesis of this disorder, its clinical manifestations, evaluation and therapeutic options. DATA SOURCES: Articles on chronic abdominal pain in the recent years from PubMed, MEDLINE, and reference textbooks were reviewed. RESULTS: Chronic abdominal pain, a functional gastrointestinal disorder (FGID), is a multifactorial condition that results from a complex interaction between psychosocial and physiologic factors via the brain-gut axis. A thorough history coupled with a complete physical examination and normal screening studies rule out an organic cause in 95% of the cases. It is highly important for the physician to establish a trusting relationship with the child and parents because successful treatment including modification of physical and psychological stress factors, dietary changes, and drug therapy depends greatly on education, reassurance and active psychological support. CONCLUSIONS: FGIDs are a cause of great anxiety, distress and morbidity in children as well as adults. As our understanding of these conditions improves, our therapeutic interventions will progress not only to overcome them but also to intervene early in the disease course so as to limit long-term impact.

Laparoscopic adrenalectomy of an adrenal adenoma with myelolipoma relieves severe hypertension in a 16-year-old patient.

Adrenal adenoma with myelolipoma is extremely rare in pediatrics. Although the tumor is usually asymptomatic, sometimes it may result in serious manifestations. A 16-year-old patient was diagnosed with severe hypertension associated with a right adrenal mass. The laboratory work-up was inconclusive of the nature of the tumor. Plasma and urinary hormonal studies were not diagnostic. Magnetic resonance imaging (MRI) of the brain and meta-iodobenzylguanidine (MIBG) scanning were normal. MRI of the abdomen showed a heterogeneous adrenal mass 4.2x3.3 cm. Laparoscopic resection of the mass was done, and the pathology revealed an adrenal adenoma with myelolipoma. After tumor resection the hypertension resolved, and within 1 month the patient was off medications. At 2-year follow-up the patient's blood pressure remained normal at 120/73 mmHg. This is a case in which an adrenal adenoma with myelolipoma, a benign and usually asymptomatic tumor, presented as severe hypertension resolving with surgical resection of the tumor.