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.

North American Society for Pediatric Gastroenterology, Hepatology, and Nutrition Position Statement for Telehealth.

Telehealth (TH) broadly encompasses remote activities of clinical care (telemedicine), provider and patient education, and general health services. The use of synchronous video for TH first occurred in 1964 and then catapulted to the forefront in 2020 during the coronavirus disease 2019 public health emergency. Due to the sudden need for increased TH utilization by nearly all health care providers at that time, TH became essential to clinical practice. However, its sustainable future is unclear in part given that best practices for TH in pediatric gastroenterology (GI), hepatology, and nutrition remain undefined and non-standardized. Key areas for review include historical perspective, general and subspeciality usage, health care disparities, quality of care and the provider-patient interaction, logistics and operations, licensure and liability, reimbursement and insurance coverage, research and quality improvement (QI) priorities, and future use of TH in pediatric GI with a call for advocacy. This position paper from the Telehealth Special Interest Group of North American Society of Gastroenterology, Hepatology and Nutrition provides recommendations for pediatric GI-focused TH best practices, reviews areas for research and QI growth, and presents advocacy opportunities.

Development and Testing of a New Simplified Endoscopic Mucosal Assessment for Crohn's Disease: The SEMA-CD.

OBJECTIVES: Endoscopic mucosal improvement is the gold standard for assessing treatment efficacy in clinical trials of Crohn's disease. Current endoscopic indices are not routinely used in clinical practice. The lack of endoscopic information in large clinical registries limits their use for research. A quick, easy, and accurate method is needed for assessing mucosal improvement for clinicians in real-world practice. We developed and tested a novel simplified endoscopic mucosal assessment for Crohn's disease (SEMA-CD). METHODS: We developed a 5-point scale for ranking endoscopic severity of ileum and colon based on Simple Endoscopic Score for Crohn's disease (SES-CD). Central readers were trained to perform SES-CD and SEMA-CD. Pediatric patients with Crohn's disease undergoing colonoscopy were enrolled. Video recordings of colonoscopies were de-identified and randomly assigned to blinded central readers. The SES-CD and SEMA-CD were scored for each video. The SES-CD was considered the validated standard for comparison. Correlation was assessed with Spearman rho, inter- and intrarater reliability with kappa statistics. RESULTS: Fifty-seven colonoscopies were read a total of 212 times. Correlation between SEMA-CD and SES-CD was strong (rho = 0.98, P < 0.0001). Inter-rater reliability for SEMA-CD was 0.80, and intrarater reliability was 0.83. Central readers rated SEMA-CD as easier than SES-CD. CONCLUSION: The SEMA-CD accurately and reproducibly correlates with the standard SES-CD. Central readers viewed SEMA-CD as easier than SES-CD. Use of SEMA-CD in practice should enable collecting mucosal improvement information in large populations of patients. This will improve the quality of research that can be conducted in clinical registries. External validation is needed.

Implementing a Novel Quality Improvement-Based Approach to Data Quality Monitoring and Enhancement in a Multipurpose Clinical Registry.

OBJECTIVE: To implement a quality improvement based system to measure and improve data quality in an observational clinical registry to support a Learning Healthcare System. DATA SOURCE: ImproveCareNow Network registry, which as of September 2019 contained data from 314,250 visits of 43,305 pediatric Inflammatory Bowel Disease (IBD) patients at 109 participating care centers. STUDY DESIGN: The impact of data quality improvement support to care centers was evaluated using statistical process control methodology. Data quality measures were defined, performance feedback of those measures using statistical process control charts was implemented, and reports that identified data items not following data quality checks were developed to enable centers to monitor and improve the quality of their data. PRINCIPAL FINDINGS: There was a pattern of improvement across measures of data quality. The proportion of visits with complete critical data increased from 72 percent to 82 percent. The percent of registered patients improved from 59 percent to 83 percent. Of three additional measures of data consistency and timeliness, one improved performance from 42 percent to 63 percent. Performance declined on one measure due to changes in network documentation practices and maturation. There was variation among care centers in data quality. CONCLUSIONS: A quality improvement based approach to data quality monitoring and improvement is feasible and effective.

Decreasing Door-to-Door Times for Infliximab Infusions in a Children's Hospital Observation Unit.

INTRODUCTION: Children with inflammatory bowel disease (IBD) often require infliximab infusions to manage their disease. Infusions administered in the hospital setting require the patient and their families to devote many hours away from home. Changing to a rapid infusion protocol has been shown in the literature to be safe and has the potential to decrease time spent in the hospital receiving infusions. METHODS: We describe stepwise changes made over a 4-month period to improve infliximab infusion efficiency and lessen the time spent in the hospital by IBD patients and their families. These changes included the implementation of a standardized order set, defaulting to rapid infusions for eligible patients, eliminating the post-infusion observation window, and improving the pharmacy's efficiency in preparing infusion medications. We utilized several established quality improvement tools, including a smart aim, key driver diagram, plan-do-study-act cycles, and statistical process control charts to measure these interventions. RESULTS: Within three months of starting, the average door-to-door time patients spent in the hospital decreased by 128 minutes (2 hours 8 minutes). This improvement amounts to 768 minutes (12 hours 48 minutes) per year of time returned for normal childhood activities outside of the hospital. There were no infusion reactions during the period monitored. CONCLUSIONS: Implementation of a rapid infliximab infusion protocol made an impressive impact on freed family time without sacrificing patient safety. The changes we implemented could be helpful to other centers interested in decreasing in-hospital time for patients with IBD and their families.

Leadership in quality improvement.

This article presents thoughts from a quality improvement team leader in a small institution application of methodology from the Institute for Healthcare Improvement. Successful leadership in quality improvement depends on structural supports in building learning systems as well as a supportive culture. Many resources can be used in quality improvement efforts. Serious students of quality improvement and leadership will seek out opportunities to learn and improve as they tailor their efforts to local needs and resources.

Disproportionate rise in Clostridium difficile-associated hospitalizations among US youth with inflammatory bowel disease, 1997-2011.

OBJECTIVES: Our aim was to characterize the temporal changes in burden that Clostridium difficile infection (CDI) added to the hospital care of children and young adults with inflammatory bowel disease (IBD) in the United States. METHODS: Retrospective analysis of annual, nationally representative samples of children and young adults with IBD. RESULTS: There was a 5-fold increase in IBD hospitalizations with CDI from 1997 to 2011 (P for trend <0.01). During the same period, IBD hospitalizations without CDI increased 2-fold (P for trend <0.01). Mean length of stay for IBD hospitalizations with CDI was consistently longer than that for hospitalizations without CDI and did not significantly change over time (P for trend = 0.47). CDI-related total hospital days in the United States rose from 1702 to 10,194 days per million individuals per year from 1997 to 2011 (P for trend <0.01). Children and young adults hospitalized with CDI had a significantly lower odds of colectomy (0.31) compared with those without CDI. Total charges for CDI-related hospitalizations among children and young adults in the United States rose from $8.7 million in 1997 to $68.2 million in 2011. CONCLUSIONS: A widening gap in burden has opened between IBD hospitalizations with and without CDI during the last decade and a half. CDI-related hospitalizations are associated with disproportionately longer lengths of stay, more hospital days, and more charges than hospitalizations without CDI over time. Further work within health systems, hospitals, and practices can help us better understand this enlarging gap to improve clinical care for this vulnerable population.

Increasing hospitalizations in inflammatory bowel disease among children in the United States, 1988-2011.

BACKGROUND: Our objective was to characterize national trends in inflammatory bowel disease (IBD)-related hospitalizations for children. We hypothesized that over time, improvements in care would be associated with a decrease in hospitalization rates, similar to what has been observed in Canadian children with IBD. METHODS: Retrospective, serial, cross-sectional analysis of annual, nationally representative samples of children with IBD. RESULTS: Overall, discharges for all children irrespective of diagnosis decreased from 1988 to 2011 (P for trend <0.001). In contrast, discharges for children with IBD rose over the same time period from 6.1 (95% confidence interval [CI], 4.0-8.2) to 8.2 (95% CI, 5.5-10.9) per 100,000 individuals per year (P for trend <0.001). More of this rise occurred in hospitalizations that did not have IBD-related endoscopy or surgery performed (P for trend <0.001). Although mean length of stay decreased over the study period (P for trend <0.001), total hospital days increased over the latter half of the study with a significant increase over the entire study period (P for trend <0.001). CONCLUSIONS: Contrary to clinically informed hypotheses, nationally representative rates of hospitalization for pediatric patients with IBD have increased since the mid-1990s. This directly contrasts with stable rates over the preceding years. Most of the expansion in hospital care seems to be related to hospitalizations that do not include procedures. Several lines of future research may greatly facilitate a better understanding of the epidemiologic, therapeutic, and health care resource issues at play.

Variation in infliximab administration practices in the treatment of pediatric inflammatory bowel disease.

OBJECTIVES: Infliximab is used increasingly to treat inflammatory bowel disease (IBD). Infliximab is supplied in 100-mg vials. Doses that are typically calculated as 5 mg · kg⁻¹ · dose⁻¹ are commonly rounded up or down to the nearest 100 mg. Variation in dosing practices is unknown. Underdosing based on weight may increase the risk for disease exacerbation, whereas overimmune suppression could increase the risk of infection. Children may be at greater risk from dosage rounding. We aimed to characterize infliximab dosing practices, the use of corticosteroid premedication, and duration of infusions among pediatric practitioners participating in the ImproveCareNow Network, a national collaboration to improve IBD care and outcomes. METHODS: A national survey of infliximab dosing practices was sent to 279 pediatric IBD practitioners from March to December 2011. Double data reconciliation, t test, and χ² analyses were performed. RESULTS: The response rate was 74% (N = 207). Thirty-eight percent (78/207) indicated that their practice has no uniform approach to the rounding of doses. Of 114 respondents indicating a uniform approach to rounding doses, 43% always round up to the nearest 100 mg, 33% always round up or down to the nearest 100 mg, and 14% never round doses. In addition, 28% of respondents always premedicate with corticosteroids and 12% never premedicate. Of respondents indicating "it depends," 95% premedicate if there has been a previous infusion reaction, 46% if there has been a prolonged lapse between treatment doses, 40% if antibodies to infliximab are present, and 11% if giving infliximab monotherapy. The duration of infusions is most often 2 hours, but varies between 1 and 4 hours. CONCLUSIONS: Wide variation exists in the practice of infliximab administration in pediatric IBD. The effect of these variations on outcomes is unknown.