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.

Using multiple imputation of real-world data to estimate clinical remission in pediatric inflammatory bowel disease.

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.

Use, Durability, and Risks for Discontinuation of Initial and Subsequent Biologics in a Large Pediatric-Onset IBD Cohort.

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.

Treatment and biologic maintenance-dosing patterns among pediatric patients with ulcerative colitis or Crohn's disease.

OBJECTIVES: To assess treatment patterns and initial and maintenance dosing of biologics over 3 years in pediatric patients with ulcerative colitis (UC) or Crohn's disease (CD), utilizing data from the ImproveCareNow registry. METHODS: Pediatric patients diagnosed with UC or CD and aged 2-17 years were included in the study. Descriptive statistics were employed to summarize baseline demographics. The proportion of patients on medication for UC or CD were analyzed at the baseline visit, 1-year, and 3-year time points (Cohort 1). Biologic maintenance dosage was calculated only for patients who had data for dose and weight at all-time points (Cohort 2). RESULTS: In Cohort 1 (UC = 1784; CD = 4720), baseline treatment in UC included corticosteroid, 5-ASA, and 6-MP/AZA; at 1-year and 3-year time points, treatment with 5-ASA and corticosteroid decreased, whereas 6-MP/AZA and anti-TNFs increased. In CD, baseline treatment included corticosteroid, anti-TNF, 6-MP/AZA, and methotrexate; use of corticosteroids decreased, whereas the use of methotrexate and anti-TNFs increased over 3 years. In Cohort 2 (UC = 350; CD = 1537), at first maintenance dose, UC patients on infliximab received a mean dose of 10.5 mg/kg/8 wk, adalimumab (weight < 40 kg and ≥40 kg) 1.3 mg/kg/2 wk and 0.8 mg/kg/2 wk, and vedolizumab 6.9 mg/kg/8 wks. At the first maintenance dose, CD patients on infliximab received a mean dose of 8.1 mg/kg/8 wk, adalimumab (weight < 40 kg) 1.1 mg/kg/2 wk, adalimumab (weight ≥ 40 kg) 0.8 mg/kg/2 wk, and vedolizumab 10.5 mg/kg/8 wks. CONCLUSION: The use of corticosteroids was common at the initial visit in patients. Anti-TNFs remain the most used class of biologics, however, reported doses in our study were substantially higher than the standard dosing guidelines.

Validating the Simplified Endoscopic Mucosal Assessment for Crohn's Disease: A Novel Method for Assessing Disease Activity.

BACKGROUND: To demonstrate treatment efficacy in Crohn's disease (CD), regulatory authorities require that trials include an endoscopic remission/response end point; however, standardized endoscopic assessment of disease activity, such as the Simple Endoscopic Score for Crohn's Disease (SES-CD), is not typically recorded by clinicians in practice or outside of clinical trials. The novel Simplified Endoscopic Mucosal Assessment for Crohn's Disease (SEMA-CD) was developed to be easy to use in routine clinical practice and as a trial end point. We conducted a study to assess and validate the reliability and feasibility of SEMA-CD as a measure of endoscopic disease activity. METHODS: Pre- and post-treatment ileocolonoscopy videos of pediatric (n = 36) and adult (n = 74) CD patients from 2 ustekinumab clinical trials were each scored with SEMA-CD by 2 to 3 professional central readers, blinded to clinical history and other video scorings; the correlation between SEMA-CD and SES-CD previously completed during the trials was assessed. Sensitivity to change, inter- and intrarater reliability, and comparative ease of scoring were also assessed. RESULTS: The SEMA-CD strongly correlated with SES-CD (Spearman ρ = 0.89; 95% confidence interval, 0.86-0.92). Pre- to post-treatment changes in SEMA-CD vs in SES-CD were strongly correlated, and the correlation remained strong between the scores when compared by study population (pediatric, adult), disease severity, and video quality. Intra- and inter-rater reliability were good, and SEMA-CD was rated easier than SES-CD to score 63.0% of the time, although slightly more difficult than SES-CD to score <1.0% of the time. CONCLUSIONS: The SEMA-CD is reliable, reproducible, sensitive to change, and easy to use in both pediatric and adult patients with CD.

Quantification of Mucosal Activity from Colonoscopy Reports via the Simplified Endoscopic Mucosal Assessment for Crohn's Disease.

BACKGROUND: Endoscopic mucosal healing is the gold standard for evaluating Crohn's disease (CD) treatment efficacy. Standard endoscopic indices are not routinely used in clinical practice, limiting the quality of retrospective research. A method for retrospectively quantifying mucosal activity from documentation is needed. We evaluated the simplified endoscopic mucosal assessment for CD (SEMA-CD) to determine if it can accurately quantify mucosal severity recorded in colonoscopy reports. METHODS: Pediatric patients with CD underwent colonoscopy that was video recorded and evaluated via Simple Endoscopic Score for CD (SES-CD) and SEMA-CD by central readers. Corresponding colonoscopy reports were de-identified. Central readers blinded to clinical history and video scoring were randomly assigned colonoscopy reports with and without images. The SEMA-CD was scored for each report. Correlation with video SES-CD and SEMA-CD were assessed with Spearman rho, inter-rater, and intrarater reliability with kappa statistics. RESULTS: Fifty-seven colonoscopy reports were read a total of 347 times. The simplified endoscopic mucosal assessment for CD without images correlated with both SES-CD and SEMA-CD from videos (rho = 0.82, P < .0001 for each). The addition of images provided similar correlation. Inter-rater and intrarater reliability were 0.93 and 0.92, respectively. CONCLUSIONS: The SEMA-CD applied to retrospective evaluation of colonoscopy reports accurately and reproducibly correlates with SES-CD and SEMA-CD of colonoscopy videos. The SEMA-CD for evaluating colonoscopy reports will enable quantifying mucosal healing in retrospective research. Having objective outcome data will enable higher-quality research to be conducted across multicenter collaboratives and in clinical registries. External validation is needed.

Clinical Outcome Assessments in Pediatric Patients With Ulcerative Colitis and Crohn's Disease Receiving Biologics: A Retrospective Cohort Study.

Background: To assess disease activity, steroid-free remission, and other clinical outcome assessments among pediatric patients with ulcerative colitis (UC) and Crohn's disease (CD) in the ImproveCareNow (ICN) registry. Methods: Patients aged 2-17 years diagnosed with UC or CD between June 1, 2013 and December 31, 2019 were enrolled if they initiated a biologic after enrollment in the ICN registry and completed at least 12 months follow-up after first maintenance dose. Baseline (at biologic initiation) demographics were summarized using descriptive statistics. Pediatric UC Activity Index (PUCAI), partial Mayo score, and Physician Global Assessment (PGA) were assessed for UC; and the Short Pediatric Crohn's Disease Activity Index (sPCDAI) and PGA were assessed for CD at first maintenance dose, 1- and 3-year time points. Kappa coefficients were used to assess the level of agreement between the outcome measures. Results: A total of 1887 patients (UC = 350; CD = 1537) were included. Baseline demographics were similar across groups. For UC patients, mean PUCAI scores decreased and the proportion of patients in steroid-free remission, quiescent state based on PGA, and remission based on partial Mayo score increased from first maintenance dose to 1 and 3 years. For CD patients, mean sPCDAI score of CD patients decreased and the proportion of patients in steroid-free remission by sPCDAI and in quiescent state based on PGA increased from first maintenance dose to 1 and 3 years. Kappa coefficients showed only modest correlation between disease activity assessments. Conclusions: Disease activity scores improved over time, with more pediatric patients with UC and CD achieving steroid-free remission at 1 and 3 years after first biologic maintenance dose.

Continued Statural Growth in Older Adolescents and Young Adults With Crohn's Disease and Ulcerative Colitis Beyond the Time of Expected Growth Plate Closure.

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.

Quality Items Required for Running a Paediatric Inflammatory Bowel Disease Centre: An ECCO Paper.

BACKGROUND: The importance of a holistic approach with a comprehensive multidisciplinary team, including nutritional and psychosocial support, is becoming well recognised as a key contributor to optimal care in paediatric inflammatory bowel disease [IBD]. The Paediatric committee of ECCO [P-ECCO] aimed to determine important components that would contribute to quality of care in a paediatric IBD centre [henceforth 'quality items']. METHODS: First, a list of items has been generated by a Delphi group of 111 international paediatric IBD experts. Through an iterative process, the group graded and ranked the items according to their perceived relative contribution to quality care. We then surveyed 101 paediatric IBD centres affiliated with the Porto and Interest groups of ESPGHAN in Europe and with the ImproveCareNow registry in North America, exploring the availability of the retained items in their centres. RESULTS: A total of 68 items were generated and reduced to a list of 60 ranked order items, grouped in six domains: Facility, Personnel, Management, Supportive Services, Patient Support and Accessibility, and Academia and Communications. Of the retained items, 52 [88%] were present in most of the 101 high-performing paediatric IBD centres, and there was a trend for increased availability with increased patient volume at the centres. CONCLUSION: In this P-ECCO study, we attempted to tabulate, for the first time in paediatrics, 60 quality items that paediatric IBD referral centres may wish to include.

Infliximab Is Not Associated With Increased Risk of Malignancy or Hemophagocytic Lymphohistiocytosis in Pediatric Patients With Inflammatory Bowel Disease.

BACKGROUND AND AIMS: Immunosuppressive therapy for inflammatory bowel disease (IBD) in pediatric patients is thought to increase the risk of malignancy and lymphoproliferative disorders, including hemophagocytic lymphohistiocytosis (HLH). We compared unadjusted incidence rates of malignancy and HLH in pediatric patients with IBD exposed to infliximab (IFX) with patients not exposed to biologics and calculated standardized incidence ratios (SIRs). METHODS: We collected and analyzed data from 5766 participants in a prospective study of long-term outcomes of pediatric patients with IBD (NCT00606346), from May 31, 2007 through June 30, 2016. Patients were 17 years old or younger and had Crohn's disease, ulcerative colitis, or IBD-unclassified with 24,543.0 patient-years of follow-up. We estimated incidence rates for malignancy and HLH as events/1000 patient-years of follow-up. We calculated age-, sex-, and race-adjusted SIRs, with 95% confidence intervals (CIs), using the Surveillance, Epidemiology, and End Results Program (SEER) database. RESULTS: Thirteen of the 15 patients who developed a malignancy and all 5 of the patients who developed HLH had been exposed to thiopurines; 10 patients with malignancy had also been exposed to a biologic agent. Unadjusted incidence rates showed no increased risk of malignancy (0.46/1000 patient-years) or HLH (0.0/1000 patient-years) in patients exposed to IFX as the only biologic vs those unexposed to biologics (malignancy: 1.12/1000 patient-years; HLH: 0.56/1000 patient-years). SIRs did not demonstrate an increased risk of malignancy among patients exposed to IFX (SIR, 1.69; 95% CI, 0.46-4.32) vs patients not exposed to a biologic agent (SIR, 2.17; 95% CI, 0.59-5.56), even when patients were stratified by thiopurine exposure. CONCLUSIONS: In determination of age-, sex-, and race-adjusted SIRs using data from a large clinical study and the SEER database, we found that IFX exposure did not associate with increased risk of malignancy or HLH in pediatric patients with IBD. Thiopurine exposure is an important precedent event for the development of malignancy or HLH in pediatric patients with IBD.

Health Insurance Paid Costs and Drivers of Costs for Patients With Crohn's Disease in the United States.

OBJECTIVES: The cost of medical care for Crohn's disease (CD) and comorbidities in the era of biologics is unclear. We examined insurance claims data from US health plans to understand this relationship. METHODS: Longitudinal CD patient data and reimbursement information from 11 health plans engaged with Accordant Health Services between 2011 and 2013 were analyzed. The analysis considered data for all CD patients and for the patient subgroup ≤20 years and >20 years of age. Descriptive statistics measured the mean health-plan paid costs per patient, the relative cost contribution of anti-tumor necrosis factor (TNF) agents, and health care costs for 31 specific comorbid conditions among CD patients. RESULTS: Overall, there were 5,090 CD patients (57% women) of which 587 CD patients were ≤20 years of age. The mean health-plan paid cost per member per year was $18,637 (s.d. $32,023) for all CD patients, $22,796 (s.d. $ 41,905) for CD patients ≤20 years, and $18,095 (s.d. $30,065) for patients >20 years of age. Twenty-eight percent of CD patients accounted for 80% of total costs. No differences were found in costs based on gender. Increased health-plan paid costs were significantly correlated with the number of comorbid conditions across all ages. Pharmacy utilization costs account for nearly one-half (45.5%) of the total CD-attributable costs, exceeding inpatient care costs. Anti-TNF agents alone comprised nearly one-third (29.5%) of total costs. Aside from anti-TNF costs, other major categories of expense were as follows: inpatient 23.1%, outpatient hospital setting 15.7%, and MD office 8.2%. CONCLUSIONS: Total health-care costs in CD exceed previous estimates, with the majority of costs being allocated to a relatively small subgroup of patients. Pharmacy utilization costs, owing to anti-TNF use, result in increasing total health-care costs and currently exceed costs for inpatient care. Pragmatic strategies to encourage gastroenterologists in the best clinical practice of optimizing anti-TNF use-in particular for younger age patients and those with multiple comorbidities-are necessary to reduce avoidable pharmacy utilization and inpatient care costs.

A Digital Architecture for a Network-Based Learning Health System: Integrating Chronic Care Management, Quality Improvement, and Research.

INTRODUCTION: We collaborated with the ImproveCareNow Network to create a proof-of-concept architecture for a network-based Learning Health System. This collaboration involved transitioning an existing registry to one that is linked to the electronic health record (EHR), enabling a "data in once" strategy. We sought to automate a series of reports that support care improvement while also demonstrating the use of observational registry data for comparative effectiveness research. DESCRIPTION OF ARCHITECTURE: We worked with three leading EHR vendors to create EHR-based data collection forms. We automated many of ImproveCareNow's analytic reports and developed an application for storing protected health information and tracking patient consent. Finally, we deployed a cohort identification tool to support feasibility studies and hypothesis generation. There is ongoing uptake of the system. To date, 31 centers have adopted the EHR-based forms and 21 centers are uploading data to the registry. Usage of the automated reports remains high and investigators have used the cohort identification tools to respond to several clinical trial requests. SUGGESTIONS FOR FUTURE USE: The current process for creating EHR-based data collection forms requires groups to work individually with each vendor. A vendor-agnostic model would allow for more rapid uptake. We believe that interfacing network-based registries with the EHR would allow them to serve as a source of decision support. Additional standards are needed in order for this vision to be achieved, however. CONCLUSIONS: We have successfully implemented a proof-of-concept Learning Health System while providing a foundation on which others can build. We have also highlighted opportunities where sponsors could help accelerate progress.

Feasibility and validity of the pediatric ulcerative colitis activity index in routine clinical practice.

OBJECTIVES: The Pediatric Ulcerative Colitis Activity Index (PUCAI) is a noninvasive disease activity index developed as a clinical trial endpoint. More recently, practice guidelines have recommended the use of PUCAI in routine clinical care. We therefore sought to evaluate the feasibility, validity, and responsiveness of PUCAI in a large, diverse collection of pediatric gastroenterology practices. METHODS: We extracted data from the 2 most recent encounters for patients with ulcerative colitis in the ImproveCareNow registry. Feasibility was determined by the percentage of patients for whom all PUCAI components were recorded, validity by correlation of PUCAI scores across physician global assessment (PGA) categories, and responsiveness to change by the correlation between the change in PUCAI and PGA scores between visits. RESULTS: A total of 2503 patients were included (49.5% boys, age 15.2 ±â€Š4.1 years, disease duration 3.7 ±â€Š3.2 years). All items in the PUCAI were completed for 96% of visits. PUCAI demonstrated excellent discriminatory ability between remission, mild, and moderate disease; discrimination between moderate and severe disease was less robust. There was good correlation with PGA (r = 0.76 [P < 0.001] and weighted kappa κ = 0.73 [P < 0.001]). The PUCAI change scores correlated well with PGA change scores (P < 0.001). Test-retest reliability of the PUCAI was good (intraclass correlation coefficient 0.72 [95% confidence interval 0.70-0.75], P < 0.001). Guyatt responsiveness statistic was 1.18, and the correlation of ΔPUCAI with ΔPGA was 0.69 (P < 0.001). CONCLUSIONS: The PUCAI is feasible to use in routine clinical settings. Evidence of its validity and responsiveness supports its use as a clinical tool for monitoring disease activity for patients with ulcerative colitis.

Routine use of thiopurines in maintaining remission in pediatric Crohn's disease.

AIM: To evaluate the effectiveness of thiopurines in maintaining steroid-free remission in routine clinical practice. METHODS: The multi-center Pediatric Inflammatory Bowel Disease Network (PIBDNet) cohort study prospectively collected data on thiopurine naïve patients initiating mercaptopurine (6MP) or azathioprine. Patients with a diagnosis of Crohn's disease (CD) were included in our study upon entering remission as determined by physician global assessment (PGA) within 365 d of initiation of thiopurines. The primary outcome of the study was maintenance of steroid-free remission (SFR) at each follow up visit. Patients were considered treatment failures if there had been a change in PGA from remission to mild, moderate or severe disease; disease relapse between visits; need for rescue therapy (biologic therapy, methotrexate, steroids); thiopurine discontinuation, hospitalization or surgical intervention. A secondary outcome defined treatment failure as a change from remission to moderate or severe (not mild) in addition to the previously defined criteria. RESULTS: Sixty-five of 182 patients in the PIBDNet registry met criteria for inclusion in this study. Forty-five of 65 (69%) of included patients achieved remission within 180 d of thiopurine initiation. For the primary outcome, 47% and 23% of patients remained in SFR at 6 and 12 mo. The mean thiopurine dose at initiation for the 65 included patients was 0.89 ± 0.31 mg/kg per day. Metabolite levels were obtained in 48% (31/65) of the included patients with a mean 6TG level of 258 pmole/8 × 10(8) RBC ± 147. For the secondary outcome, 65% and 42% of patients remained in SFR at 6 and 12 mo. CONCLUSION: Thiopurines were less effective in maintaining remission for pediatric CD in this "real world" cohort than has been previously described. Variation in thiopurine dosing and metabolite measurement was found among practitioners.

PEDSnet: how a prototype pediatric learning health system is being expanded into a national network.

Except for a few conditions, pediatric disorders are rare diseases. Because of this, no single institution has enough patients to generate adequate sample sizes to produce generalizable knowledge. Aggregating electronic clinical data from millions of children across many pediatric institutions holds the promise of producing sufficiently large data sets to accelerate knowledge discovery. However, without deliberately embedding these data in a pediatric learning health system (defined as a health care organization that is purposefully designed to produce research in routine care settings and implement evidence at the point of care), efforts to act on this new knowledge, reducing the distress and suffering that children experience when sick, will be ineffective. In this article we discuss a prototype pediatric learning health system, ImproveCareNow, for children with inflammatory bowel disease. This prototype is being scaled up to create PEDSnet, a national network that will support the efficient conduct of clinical trials, observational research, and quality improvement across diseases, specialties, and institutions.

Appropriateness of emergency department use in pediatric inflammatory bowel disease: a quality improvement opportunity.

OBJECTIVES: We sought to characterize emergency department (ED) encounters for pediatric inflammatory bowel disease (IBD) to identify areas for prevention. METHODS: Retrospective chart review of 5 consecutive ED encounters at 7 centers was performed. RESULTS: Of 35 unique encounters by 32 patients, 3 main factors contributed to ED utilization: disease severity or course, day or time of care, and physician instruction. Of the ED encounters, approximately one-fifth were judged medically unnecessary, and one-half avoidable in a more optimal health care system. CONCLUSIONS: ED visits by pediatric patients with IBD may be reduced in a more optimal health care system.

Effectiveness of anti-TNFα for Crohn disease: research in a pediatric learning health system.

OBJECTIVES: ImproveCareNow (ICN) is the largest pediatric learning health system in the nation and started as a quality improvement collaborative. To test the feasibility and validity of using ICN data for clinical research, we evaluated the effectiveness of anti-tumor necrosis factor-α (anti-TNFα) agents in the management of pediatric Crohn disease (CD). METHODS: Data were collected in 35 pediatric gastroenterology practices (April 2007 to March 2012) and analyzed as a sequence of nonrandomized trials. Patients who had moderate to severe CD were classified as initiators or non-initiators of anti-TNFα therapy. Among 4130 patients who had pediatric CD, 603 were new users and 1211 were receiving anti-TNFα therapy on entry into ICN. RESULTS: During a 26-week follow-up period, rate ratios obtained from Cox proportional hazards models, adjusting for patient and disease characteristics and concurrent medications, were 1.53 (95% confidence interval [CI], 1.20-1.96) for clinical remission and 1.74 (95% CI, 1.33-2.29) for corticosteroid-free remission. The rate ratio for corticosteroid-free remission was comparable to the estimate produced by the adult SONIC study, which was a randomized controlled trial on the efficacy of anti-TNFα therapy. The number needed to treat was 5.2 (95% CI, 3.4-11.1) for clinical remission and 5.0 (95% CI, 3.4-10.0) for corticosteroid-free remission. CONCLUSIONS: In routine pediatric gastroenterology practice settings, anti-TNFα therapy was effective at achieving clinical and corticosteroid-free remission for patients who had Crohn disease. Using data from the ICN learning health system for the purpose of observational research is feasible and produces valuable new knowledge.