Background: Biologic medications are recommended for treatment of moderately-to-severely active Crohn disease (CD) or ulcerative colitis (UC) in children. However, many patients require sequential biologic treatment because of nonresponse or loss of response to the initial biologic.Methods: We analyzed pediatric inflammatory bowel disease (IBD) data from the ImproveCareNow Network registry between May 2006 and September 2016, including time to biologic initiation, choice of first subsequent biologics, biologic durability, and reasons for discontinuation.Results: Of 17,649 patients with IBD [CD: 12,410 (70%); UC: 5239 (30%)], 7585 (43%) were treated with a biologic agent before age 18 (CD: 50%; UC: 25%). Biologic treatment was more likely for CD than UC (odds ratio, 3.0; 95% CI: 2.8-3.2; P < 0.0001). First biologic agents for all patients were anti-tumor necrosis factor agents (88% infliximab, 12% adalimumab). Probability of remaining on the first biologic was significantly higher in CD than UC (P < 0.0001). First biologics were discontinued because of loss of response (39%), intolerance (23%), and nonresponse (19%). In univariate analysis, factors associated with discontinuation of first and/or second biologics in CD include colonic-only disease, corticosteroid use, upper gastrointestinal tract involvement, and clinical and biochemical markers of severe disease. Biologic durability improved with later induction date.Conclusions: Treatment with biologic medications is common in pediatric IBD. Patients with CD are more likely to receive biologics, receive biologics earlier in disease course, and remain on the first biologic longer than patients with UC. Multiple factors may predict biologic durability in children with IBD.

Aim: To evaluate the performance of the multiple imputation (MI) method for estimating clinical effectiveness in pediatric Crohn's disease in the ImproveCareNow registry; to address the analytical challenge of missing data. Materials & methods: Simulation studies were performed by creating missing datasets based on fully observed data from patients with moderate-to-severe Crohn's disease treated with non-ustekinumab biologics. MI was used to impute sPCDAI remission statuses in each simulated dataset. Results: The true remission rate (75.1% [95% CI: 72.6%, 77.5%]) was underestimated without imputation (72.6% [71.8%, 73.3%]). With MI, the estimate was 74.8% (74.4%, 75.2%). Conclusion: MI reduced nonresponse bias and improved the validity, reliability, and efficiency of real-world registry data to estimate remission rate in pediatric patients with Crohn's disease.

There are limited data on the impact of COVID-19 in children with a kidney transplant (KT). We conducted a prospective cohort study through the Improving Renal Outcomes Collaborative (IROC) to collect clinical outcome data about COVID-19 in pediatric KT patients. Twenty-two IROC centers that care for 2732 patients submitted testing and outcomes data for 281 patients tested for SARS-CoV-2 by PCR. Testing indications included symptoms and/or potential exposures to COVID-19 (N = 134, 47.7%) and/or testing per hospital policy (N = 154, 54.8%). Overall, 24 (8.5%) patients tested positive, of which 15 (63%) were symptomatic. Of the COVID-19-positive patients, 16 were managed as outpatients, six received non-ICU inpatient care and two were admitted to the ICU. There were no episodes of respiratory failure, allograft loss, or death associated with COVID-19. To estimate incidence, subanalysis was performed for 13 centers that care for 1686 patients that submitted all negative and positive COVID-19 results. Of the 229 tested patients at these 13 centers, 10 (5 asymptomatic) patients tested positive, yielding an overall incidence of 0.6% and an incidence among tested patients of 4.4%. Pediatric KT patients in the United States had a low estimated incidence of COVID-19 disease and excellent short-term outcomes.

BACKGROUND:Cessation of statural growth occurs with radiographic closure of the growth plates, radiographically defined as bone age (BA) 15 years in females and 17 in males.METHODS:We determined the frequency of continued growth and compared the total height gain beyond the time of expected growth plate closure and the chronological age at achievement of final adult height in Crohn's disease (CD) vs ulcerative colitis (UC) and described height velocity curves in inflammatory bowel disease (IBD) compared with children in the National Health and Nutrition Examination Survey (NHANES). We identified all females older than chronological age (CA) 15 years and males older than CA 17 years with CD or UC in the ImproveCareNow registry who had height documented at ≥3 visits ≥6 months apart.RESULTS:Three thousand seven patients (48% female; 76% CD) qualified. Of these patients, 80% manifested continued growth, more commonly in CD (81%) than UC (75%; P = 0.0002) and in females with CD (83%) than males with CD (79%; P = 0.012). Median height gain was greater in males with CD (1.6 cm) than in males with UC (1.3 cm; P = 0.0004), and in females with CD (1.8 cm) than in females with UC (1.5 cm; P = 0.025). Height velocity curves were shifted to the right in patients with IBD vs NHANES.CONCLUSIONS:Pediatric patients with IBD frequently continue to grow beyond the time of expected growth plate closure. Unexpectedly, a high proportion of patients with UC exhibited continued growth, indicating delayed BA is also common in UC. Growth, a dynamic marker of disease status, requires continued monitoring even after patients transition from pediatric to adult care.

remaining colectomy-free at 3, 6, 12, 24 and 36 months was 97%, 94%, 86%, 80% and 70%.14 hospitalizations occurred in 8 patients, and 5 serious infections occurred in 5 patients.Concomitant immunomodulator therapy did not appear to improve outcomes.Conclusions: Durable rates of steroid-free remission were observed in pediatric patients with UC on ADA in routine practice.Of patients followed for 24 months, 97% of patients remained on ADA and approximately 70% of patients were in steroid-free clinical remission.80% of patients remained colectomy-free for 24 months.Table percentages are calculated based on non-missing values Su2023

Tumour necrosis factor inhibitors (TNFi) are effective in treating children with moderately to severely active ulcerative colitis (UC) and Crohn’s disease (CD). However, nonresponse or loss of response to therapy may lead to sequential biologic treatment. Factors associated with TNFi discontinuation in children are not well known. The aim of this study was to assess for clinical factors associated with first and subsequent TNFi discontinuation in a large paediatric inflammatory bowel disease (IBD) cohort. We performed a retrospective study using data from ImproveCareNow (ICN), a multicentre, prospective paediatric IBD registry. Patients with CD and UC who were treated with their first TNFi after enrolment into ICN were identified at 39 participating ICN sites. Clinical information was obtained from the ICN database and chart review. The association of factors with TNFi discontinuation was assessed with Cox regression analysis. Eight hundred and forty-six patients (678 CD, 168 UC) who fulfilled inclusion criteria were identified. Infliximab (IFX) was used first in 89% of CD patients, while 11% received adalimumab (ADA) first. On univariate analysis, discontinuation of the first TNFi in CD was associated with colonic only vs. ileocolonic disease location (hazard ratio (HR), 1.94; 95% confidence interval (CI), 1.28–2.94, p = 0.002) and higher shortPCDAI (HR, 1.01 per 1 unit increase in shortPCDAI; 95% CI 1.00–1.02, p = 0.032) and prednisone use (HR, 1.49; 95% CI 1.07–2.08, p = 0.017) at the time of TNFi initiation. Concomitant immunomodulator therapy was not shown to be associated with first TNFi discontinuation (p = 0.23) (Figure 1). Kaplan–Meier analysis of the effect of immunomodulator use within the first 6 months of first TNF inhibitor treatment on TNF inhibitor durability in paediatric Crohn’s disease, p = 0.23. Discontinuation of the second TNFi (86% ADA, 14% IFX) in CD was associated with abnormal C-reactive protein (HR 3.33; 95% CI 1.05–10.55, p = 0.041), lower albumin (p = 0.006) and haematocrit (p = 0.032) at the time of second biologic initiation, and the presence of upper gastrointestinal (GI) tract CD (HR, 3.25; 95% CI 1.13–9.35, p = 0.029). IFX was used first in 94% of UC patients, while 6% received ADA first. Discontinuation of the first TNFi in UC was more common with ADA compared with IFX (HR, 2.43; 95% CI 1.02–5.80, p = 0.045). None of these clinical variables were significant in multivariable analysis. Multiple factors associated with TNFi discontinuation in paediatric IBD patients were identified, including colonic only and upper GI tract CD location as well as markers of more severe CD. Prospective studies are needed to confirm these findings.

Biological agents (BA) are indicated for treatment of children with moderately to severely active ulcerative colitis (UC) and Crohn’s disease (CD). However, many children do not respond or lose response and require sequential BA treatment. The aims of this study were to determine the frequency and patterns of initial and sequential BA use and BA durability in a large paediatric inflammatory bowel disease (IBD) cohort. We performed a retrospective study using data from ImproveCareNow (ICN), a multicentre paediatric IBD registry. BA use and other clinical data were obtained directly from the ICN database. A subset of registry patients who were treated with their first BA after enrolment into ICN (chart review cohort), had additional clinical information obtained by chart review at 39 participating ICN sites. Of the 17649 IBD patients (12410 CD, 5239 UC) diagnosed before 18 years of age, 7585 (43%) were treated with a BA before age 18, including 50.5% of CD patients. CD patients were more likely to be treated with a BA than UC patients (odds ratio, 3.0; 95% confidence interval, 2.8–3.2; p ≤ 0.0001). In the chart review cohort (n = 1029: 809 CD, 220 UC), the first BA was an anti-TNF agent in all cases (88% infliximab, 12% adalimumab). The median time from diagnosis to BA initiation was shorter in CD than in UC (325 vs. 423 days; p = 0.004). The probability of remaining on the first BA was higher in CD than UC [0.93 vs. 0.84 at 6 month old; 0.85 vs. 0.75 at 12 month old; 0.79 vs. 0.66 at 24 month old; 0.74 vs. 0.55 at 36 month old; p = <0.0001, Figure 1]. Kaplan–Meier analysis of continuation of 1st biological agent over time by IBD diagnosis [Crohn’s disease (CD, N = 772), ulcerative colitis (UC, N = 206), log-rank test, p = < 0.0001]. Fifty-one patients excluded due to missing time or discontinuation status. The most common reasons for discontinuation of the first BA in all patients were secondary loss of response (39%), intolerance (23%), and primary non-response (PNR) (19%). PNR was a more common reason for discontinuation in UC than in CD (29% vs. 15%, p = 0.02). Over a median follow-up of 1.56 years [interquartile range, 0.89–2.57 years], 17%, 2.3%, and 0.6% of patients were treated with at least two, three, or four BAs, respectively. The second BA was most commonly an anti-TNF agent (94.8%). Vedolizumab was the second BA in 4.6% of cases and the third in 37.5% of cases. In CD, the probability of remaining on the second BA was 0.85, 0.76, 0.72, and 0.64 at 6 months, 12 months, 24 months, and 36 months, respectively. In this large cohort, BAs were used in >25% of children with UC and >50% of children with CD before 18 years of age. BA discontinuation and sequential BA treatment was relatively common. BAs were used earlier and the first BA was more durable in CD than in UC.

Adalimumab (ADA) is an anti-tumour necrosis factor agent approved for the treatment of ulcerative colitis (UC) in adults. We assessed the duration and effectiveness of ADA in paediatric UC patients in clinical practice. In a retrospective cohort study using registry data from 47 centres in the USA in the ImproveCareNow network, patients with UC treated with ADA prior to 18 years old with at least one follow-up visit were identified. Clinical care and frequency of visits were decided by the patient, parent, and clinician. Data from clinical care visits were assessed every 3 ± 1.5 months for 1 year, then every 6 ± 3 months through 3 years. If a patient had no visit during that period but was still active in the registry, the result from the previous visit was carried forward (for up to 9 months). The analysis population consisted of patients still on ADA at the respective visit after imputation. Patients’ data were excluded from analyses after a colectomy. Steroid-free clinical remission rates per Physician Global Assessment (PGA, inactive) and Pediatric Ulcerative Colitis Activity Index (PUCAI, <10) were assessed. Descriptive statistics, Kaplan–Meier analysis for colectomy rate, and Fisher’s exact test for associations between concomitant therapy and outcomes were performed. One hundred and thirty-three UC patients (24% <13 years old at therapy onset; 58% female) received ADA between August 2008 and November 2016 (Table 1). At months 3, 6, 12, 24, and 36 post-initiation, 130, 119, 76, 34, and 16 patients were followed; 89%, 78%, 80%, 97%, and 75% of followed patients remained on ADA. Of patients on ADA at 3, 6, 12, 24, and 36 months: 37%, 57%, 68%, 71%, and 73% were in steroid-free clinical remission by PGA; and 30%, 45%, 63%, 68%, and 82% by PUCAI. Table percentages are calculated based on non-missing values. The probability of remaining colectomy-free at 3, 6, 12, 24, and 36 months was 97%, 94%, 86%, 80%, and 70%. 14 hospitalisations occurred in eight patients, and five serious infections occurred in five patients. Concomitant immunomodulator therapy did not appear to improve outcomes. Durable rates of steroid-free remission were observed in paediatric patients with UC on ADA in routine practice. Of patients followed for 24 months, 97% of patients remained on ADA and approximately 70% of patients were in steroid-free clinical remission. 80% of patients remained colectomy-free for 24 months.

remaining colectomy-free at 3, 6, 12, 24 and 36 months was 97%, 94%, 86%, 80% and 70%.14 hospitalizations occurred in 8 patients, and 5 serious infections occurred in 5 patients.Concomitant immunomodulator therapy did not appear to improve outcomes.Conclusions: Durable rates of steroid-free remission were observed in pediatric patients with UC on ADA in routine practice.Of patients followed for 24 months, 97% of patients remained on ADA and approximately 70% of patients were in steroid-free clinical remission.80% of patients remained colectomy-free for 24 months.Table percentages are calculated based on non-missing values Su2023

Background: Adalimumab is an anti-tumor necrosis factor (ATNF) agent approved for the treatment of Crohn's disease in children since September 2014. We assessed the duration and effectiveness of adalimumab treatment in pediatric Crohn's disease patients in clinical practice without prior ATNF therapy. Methods: In a retrospective cohort study using registry data from clinical care visits at 43 centers in the USA in the ImproveCareNow Network, ATNF-naïve patients induced with adalimumab prior to 18 years old with at least one post-induction visit were identified. We assessed the duration of treatment and the clinical effectiveness of adalimumab based on steroid-free clinical remission using Physician Global Assessment (PGA, inactive) and Short Pediatric Crohn's Disease Activity Index (sPCDAI, ≤10), as well as steroid-free clinical response using PGA (inactive or mild) and sPCDAI (≤25). Clinical care and frequency of visits were decided by the patient, parent and clinician. Data from clinical care visits were assessed every 3±1.5 months for 1 year, then every 6±3 months through 3 years. Descriptive statistics, Fisher's Exact Test and multivariable logistic regression analyses were performed. Results: There were 174 patients (57% male, 25% <13 years old at induction) treated with adalimumab from August 2008 to December 2015. The number of patients followed post-induction for 3, 6, 12, 24 and 36 months was: 174, 174, 154, 71 and 39; the percentage of followed patients remaining on adalimumab was: 100%, 95%, 94%, 97% and 80%. Of patients on adalimumab at 3, 6, 12, 24 and 36 months: 69%, 75%, 79%, 94% and 81% were in steroid-free clinical remission by PGA; and 71%, 77%, 80%, 91% and 86% by sPCDAI. Of patients on adalimumab at 3, 6, 12, 24 and 36 months: 88%, 91%, 93%, 99% and 94% had a steroid-free clinical response by PGA; and 83%, 85%, 91%, 98% and 100% by sPCDAI. Concomitant immunomodulator therapy did not appear to improve outcomes. Conclusions: In the largest series with the longest follow-up, adalimumab was durable and effective as initial ATNF therapy for pediatric Crohn's disease in clinical practice. Of patients followed for 24 months, 97% remained on adalimumab. Steroid-free clinical remission was achieved in 91%–94%, and steroid-free clinical response in 98%–99%, of patients who remained on adalimumab for 24 months. The effect of dosage on outcomes is being investigated. These findings are important for patients, parents and clinicians considering ATNF therapy.