Multicenter Cohort Study of Infliximab Pharmacokinetics and Therapy Response in Pediatric Acute Severe Ulcerative Colitis.

BACKGROUND & AIMS: We aimed to model infliximab (IFX) pharmacokinetics (PK) in pediatric acute severe ulcerative colitis (ASUC) and assess the association between PK parameters, including drug exposure, and clinical response. METHODS: We studied a multicenter prospective cohort of hospitalized children initiating IFX for ASUC or IBD-unclassified. Serial IFX serum concentrations over 26 weeks were used to develop a PK model. We tested the association of PK parameter estimates with day 7 clinical response, week 8 clinical remission, week 26 corticosteroid-free clinical remission (CSF-CR) (using the Pediatric Ulcerative Colitis Activity Index), and colectomy-free survival. RESULTS: Thirty-eight participants received IFX (median initial dose, 9.9 mg/kg). Day 7 clinical response, week 8 clinical remission, and week 26 CSF-CR occurred in 71%, 55%, and 43%, respectively. Albumin, C-reactive protein, white blood cell count, platelets, weight, and antibodies to IFX were significant covariates incorporated into a PK model. Week 26 non-remitters exhibited faster IFX clearance than remitters (P = .013). However, cumulative IFX exposure did not differ between clinical response groups. One (2.7%) and 4 (10.8%) participants underwent colectomy by week 26 and 2 years, respectively. Day 3 IFX clearance >0.02 L/h was associated with colectomy (hazard ratio, 58.2; 95% confidence interval, 6.0-568.6; P < .001). CONCLUSIONS: At median higher-than-label IFX dosing for pediatric ASUC, baseline faster IFX CL was associated with colectomy and at week 26 with lack of CSF-CR. IFX exposure was not predictive of clinical outcomes. Higher IFX dosing may sufficiently optimize early outcomes in pediatric ASUC. Larger studies are warranted to determine whether sustained intensification can overcome rapid clearance and improve later outcomes. CLINICALTRIALS: gov identifier: NCT02799615.

Racial Disparities in Pediatric Inflammatory Bowel Disease Care: Differences in Outcomes and Health Service Utilization Between Black and White Children.

OBJECTIVE: To describe racial inequities in pediatric inflammatory bowel disease care and explore potential drivers. METHODS: We undertook a single-center, comparative cohort study of newly diagnosed Black and non-Hispanic White patients with inflammatory bowel disease, aged <21 years, from January 2013 through 2020. Primary outcome was corticosteroid-free remission (CSFR) at 1 year. Other longitudinal outcomes included sustained CSFR, time to anti-tumor necrosis factor therapy, and evaluation of health service utilization. RESULTS: Among 519 children (89% White, 11% Black), 73% presented with Crohn's disease and 27% with ulcerative colitis. Disease phenotype did not differ by race. More patients from Black families had public insurance (58% vs 30%, P < .001). Black patients were less likely to achieve CSFR 1-year post diagnosis (OR: 0.52, 95% CI:0.3-0.9) and less likely to achieve sustained CSFR (OR: 0.48, 95% CI: 0.25-0.92). When adjusted by insurance type, differences by race to 1-year CSFR were no longer significant (aOR: 0.58; 95% CI: 0.33, 1.04; P = .07). Black patients were more likely to transition from remission to a worsened state, and less likely to transition to remission. We found no differences in biologic therapy utilization or surgical outcomes by race. Black patients had fewer gastroenterology clinic visits and 2-fold increased odds for emergency department visits. CONCLUSIONS: We observed no differences by race in phenotypic presentation and medication usage. Black patients had half the odds of achieving clinical remission, but a degree of this was mediated by insurance status. Understanding the cause of such differences will require further exploration of social determinants of health.

Precision Dosing of Anti-TNF Therapy in Pediatric Inflammatory Bowel Disease.

PURPOSE OF THE REVIEW: This review focuses on recent advancements in anti-TNF therapeutic drug monitoring (TDM), pharmacogenetics and personalized drug selection for children with inflammatory bowel disease (IBD). RECENT FINDINGS: Several real-world studies and one clinical trial in children have demonstrated that proactive TDM, targeting higher exposure concentrations (> 5 µg/mL), can improve disease remission rates and enhance durability of the anti-TNF biologics. Recent data from both adult and pediatric IBD patients have revealed an association between a genetic polymorphism (HLA-DQA1*05) and the development of auto-drug antibodies. The impact of this association on clinical outcomes, considering more routine use proactive TDM and dose optimization in children, is still under investigation. Additionally, recent studies have identified potential inflammatory signatures and biomarkers that may serve as companion diagnostics for anti-TNF biologics. The effective management of anti-TNF therapies in children with IBD requires evidence-based precision dosing strategies, including routine TDM and proactive pharmacodynamic assessments.

Yield and Costs of Evaluating Children With Cyclic Vomiting Syndrome.

BACKGROUND AND OBJECTIVES: Cyclic vomiting syndrome (CVS) clinical guidelines recommend an algorithm of basic testing for standard patients, and more targeted testing, including laboratory and imaging studies, in the presence of specific red flags. The cost-effectiveness of this screening of children with suspected CVS is lacking. The objectives of this study are to determine whether screening studies in CVS patients results in diagnostic change and to estimate their healthcare cost. METHOD: Charts of patients (1-18 years) with suspected CVS were retrospectively reviewed at a single center. Results and cost of laboratory and imaging studies were analyzed. RESULTS: A total of 503 charts were reviewed from electronic medical records with the International Classification of Diseases-9 (ICD-9) code 536.2 or search terms "CVS, cyclic vomiting, persistent emesis/vomiting, hyperemesis, or intractable/ periodic vomiting." Of these, 165 (33%) had a diagnosis of CVS and 135 (82%) children (mean age 7.7 ±â€Š4.3; 73 (54%) girls) met CVS criteria based on North American Society for Pediatric Gastroenterology, Hepatology and Nutrition diagnostic criteria. Of those meeting CVS criteria, 6 (4%) had a change in management based on the CVS screening evaluation. The mean cost of screening per patient that met CVS criteria was $6125.02 and the estimated total cost for all patients who met CVS criteria was $826,877.88. CONCLUSIONS: The screening metabolic laboratory results, pelvic ultrasound, magnetic resonance imaging, and upper endoscopy resulted in a diagnosis change in few patients screened for CVS. Most children who met criteria for CVS did not benefit from screening evaluation as results did not change clinical diagnosis or management, and were associated with higher cost.

Vedolizumab Experience in Children and Adolescents With Inflammatory Bowel Disease: A Multicenter Observational Study.

Background: Vedolizumab is increasingly used off-label to treat children and adolescents with inflammatory bowel disease (IBD). In the absence of rigorous clinical trial experience, multicenter observational data are important to establish expectations for efficacy and safety. We examined 1-year outcomes following vedolizumab therapy in a large multicenter pediatric IBD cohort. Methods: We performed a retrospective study of 159 pediatric patients (4-17 years old) with IBD [78, Crohn disease (CD); 81, ulcerative colitis/IBD-unspecified (UC/IBD-U)] treated with vedolizumab for 1 year at 8 pediatric medical centers in the United States. Demographics, clinical outcomes, laboratory data, and vedolizumab dosing were recorded. The primary outcome was corticosteroid (CS)-free clinical remission at 1 year. Other measured outcomes were clinical remission at 12 and/or 24 weeks, laboratory outcomes at 1 year, and endoscopy/histology results at 1 year. Results: Among the 159 patients (mean age, 14.5 ± 2.4 years; 86% anti-TNF experienced), 68/159 (43%) achieved CS-free clinical remission at 1 year (CD, 35/78, 45%; UC/IBD-U, 33/81, 40%). Vedolizumab therapy failed and was discontinued in 33/159 (21%) patients prior to 1 year (CD, 18/78, 23%; UC/IBD-U, 15/81, 19%). While week 12 clinical remission was not predictive of 1-year clinical remission in either CD or UC/IBD-U, week 24 clinical remission was predictive of 1-year clinical remission only in CD patients. No infusion reactions or serious side effects were noted. Conclusions: Vedolizumab was safe and effective in this pediatric population with approximately 43% achieving CS-free clinical remission at 1 year. Similar efficacy was noted in both CD and UC.

Contemporary Medical Management of Acute Severe Ulcerative Colitis.

Acute severe ulcerative colitis is a medical emergency that requires prompt recognition, evaluation, and intervention. Patients require hospital admission with laboratory, radiographic, and endoscopic evaluation with initiation of corticosteroid treatment. Despite early intervention, many patients require salvage medical therapy, with some progressing to colectomy. Here we review important concepts and recent advances in the evaluation and medical management of adult and pediatric patients with acute severe ulcerative colitis.