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.

Characteristics of Pediatric Emergency Revisits After an Asthma-Related Hospitalization.

STUDY OBJECTIVE: We identify and characterize factors related to subsequent emergency revisits among children hospitalized for asthma. METHODS: This population-based, prospective, observational cohort included children aged 2 to 16 years, hospitalized for asthma at an urban pediatric facility and followed for greater than or equal to 12 months. The primary outcome was asthma-related emergency revisit within 12 months of discharge. Revisits were identified by billing codes, respiratory chief complaints, and medications administered (eg, albuterol, systemic corticosteroids), dispensed, or prescribed. Predictors and covariates include demographic, socioeconomic, access, and environmental exposure variables collected during index admission. Multivariable logistic regression was used to evaluate the association between predictors and odds of asthma-related revisit. RESULTS: A total of 671 children were enrolled; the majority were boys (65%), aged 4 to 11 years (59%), black (59%), and publicly insured (73%). There were 274 patients (41%) who were treated for asthma-related emergency revisits within 12 months of the index admission. In adjusted models, younger children, black children, children with excellent reported access to primary care, and children with a history of inhaled steroids were more likely to experience emergency revisits. Low income, detectable cotinine levels, and traffic exposure did not independently predict revisit. CONCLUSION: Asthma-related emergency revisit is common after hospitalization, with more than 40% of children returning within 12 months. Socioeconomic and exposure-related risk factors typically predictive of asthma morbidity were not independently associated with emergency revisit among children in this cohort.

Routinely sleeping away from home and the association with child asthma readmission.

The increased prevalence of transitions between households may have implications for child asthma morbidity. We, therefore, sought to enumerate the prevalence of regularly spending nights sleeping away from home among children admitted to the hospital for asthma and to examine the relationship of nights away to asthma-related readmission. This was a population-based, prospective cohort of 774 children, aged 1-16 years, who were admitted with asthma or bronchodilator-responsive wheezing and enrolled in the Greater Cincinnati Asthma Risks Study. The study took place at Cincinnati Children's Hospital Medical Center, an urban, academic children's hospital in the Midwest. The primary exposure was regularly spending nights away from home. Selected covariates included caregiver marital status, shift work, child's race, income, psychological distress, and running out of/not having medications on hand. The primary outcome was asthma-related readmission within 12 months. A total of 19 % were readmitted within 12 months. The 33 % of children that spent ≥1 night away from home per week were significantly more likely to be readmitted than those who spent no nights away (25 % vs. 16 %, p = 0.002). Spending nights away from home [adjusted relative risk (aRR) 1.5, 95 % confidence interval (CI) 1.2-2.0] and lower income (aRR 2.6, 95 % CI 1.1-6.4) were the strongest independent predictors of readmission after adjusting for child age, gender, and race, and caregiver marital status, shift work, risk of psychological distress, and running out of meds. Increased awareness of the multiple settings in which children with asthma live may help shape more comprehensive approaches to asthma care.