Proactive therapeutic drug monitoring and vedolizumab dose optimization in children with inflammatory bowel disease.

OBJECTIVES: Therapeutic drug monitoring (TDM) and dose optimization have been shown to improve clinical outcomes with antitumor necrosis factor and recent studies in adults suggest an exposure-response relationship with drug levels associated with improved clinical outcomes. However, these levels are not universally recognized as therapeutic targets for vedolizumab dosing. We aimed to assess the impact of a TDM quality improvement (QI) initiative on 52-week clinical outcomes and describe proactively obtained vedolizumab levels during the induction period in children with inflammatory bowel disease (IBD). METHODS: A QI initiative to proactively obtain TDM levels at Week 6 was implemented in 2019. A retrospective review of pediatric patients with IBD treated with vedolizumab from 2018 to 2022 was performed. Baseline demographic data, medication dosing details, disease characteristics, lab results, and 12-month clinical outcomes were recorded. For this study, we defined therapeutic target levels (>20 µg/mL at Week 6 and >12 µg/mL during maintenance) based on existing data correlating these levels with improved clinical outcomes. RESULTS: Fifty-nine patients (31 Crohn disease [CD], 28 ulcerative colitis [UC]/indeterminate colitis [IC]) were included in the study. In total, 68% (40/59) of patients had vedolizumab levels at Week 6 and 90% (53/59) had levels drawn at Week 6 or 14. Thirty-five percent of Week 6 trough levels were below our defined target of 20 µg/mL. Fifty-two of 59 patients had available data at 52 weeks. Over 80% (42/52) of patients remained on vedolizumab 52 weeks after initiation (CD 79% [23/29], UC/IC 83% [19/23]). Sixty-two percent (26/42) of patients that remained on vedolizumab at 52 weeks were treated with an intensified dosing interval of <8 weeks. Thirty-one of these 42 (74%) were in clinical remission (CR) rate at 52 weeks with 29/42 (69%) in corticosteroid-free remission. The CR rate for the entire cohort including those who discontinued therapy due to a lack of efficacy before 52 weeks was 60% (31/52). CONCLUSION: Proactive TDM and early dose optimization with vedolizumab may improve drug durability and clinical outcomes in pediatric patients with IBD.

Diagnosis and Treatment of Iron Deficiency and Anemia in Youth With Inflammatory Bowel Disease.

OBJECTIVES: Iron deficiency (ID) with and without anemia is prevalent in children and adults diagnosed with inflammatory bowel disease (IBD), but often goes unrecognized. We hypothesized, quality improvement (QI) methodology could increase the screening for and treatment of ID in children newly diagnosed with IBD. METHODS: We developed and implemented an easy-to-follow algorithm to facilitate screening for and treatment of ID for patients diagnosed with IBD. Through a series of Plan-Do-Study-Act cycles, the approach was modified to increase screening and treatment of ID. Data between January 2019 and July 2021 were assessed using statistical process control. RESULTS: Among patients newly diagnosed with IBD, 298 patients were included (67% Crohn disease, 29% ulcerative colitis, 4% indeterminate colitis, and 56% males). Rates of ID screening increased significantly from a baseline of 20% to >90%. Of the 232 patients screened for ID during the improvement period, 205 (88%) met criteria for either iron deficiency anemia (IDA) or ID at diagnosis, specifically, 151 (65%) met criteria for IDA and 54 (23%) met criteria for ID. CONCLUSIONS: Use of QI methodology to standardize screening assessments for ID among children newly diagnosed with IBD improved screening rates from a baseline of 20% to >90%, with 88% of patients found to have IDA or ID.

Improving Hepatitis B Vaccination Rates among At-risk Children and Adolescents with Inflammatory Bowel Disease.

Patients with inflammatory bowel disease (IBD) receiving tumor necrosis factor alpha inhibitors (TNFai) may be at higher risk for hepatitis B virus (HBV) infection. We conducted a quality improvement (QI) initiative to improve HBV vaccination rates in seronegative children with IBD. Methods: This QI initiative implemented an HBV vaccination strategy from September 2018 to March 2020 in patients with newly diagnosed IBD with hepatitis B surface antibody (HBsAb) <10 mIU/mL. The project aimed to (1) increase HBV vaccination rates in seronegative patients and (2) document immunogenicity after completing a three-dose vaccine series. Outcome measures included the percentage of seronegative patients who received HBV vaccines (dose 1 and three-dose series). Interventions included applying a standardized vaccination protocol, and creating a vaccine workflow in two clinical areas, previsit planning and stakeholder engagement. Results: One hundred seventy-four children and adolescents with IBD were evaluated during the study period, and 132 (76%) were HBsAb negative. After plan-do-study-act (PDSA) 1, the proportion of eligible patients who received HBV vaccine dose 1 increased from a baseline of 7% to 100% and was sustained for over 12 months. During PDSA 2, the proportion of patients completing the three-dose vaccine series improved from a baseline of 0% to 82% (n = 100); among 93 children in this subgroup who had repeat serology performed, 86 (92%) demonstrated serologic evidence of HBV protection. Conclusions: A multidisciplinary approach applying QI methodology allowed for improved and sustained HBV vaccination rates in at-risk seronegative children and adolescents with IBD. A three-dose HBV vaccine series proved immunogenic in 92% of eligible patients.

The Pediatric Inflammatory Bowel Disease Medical Home: A Proposed Model.

Care for patients with inflammatory bowel disease (IBD) can be complex and costly. Care delivery models to address these challenges and improve care quality are essential. The patient-centered medical home (PCMH), which was developed in the primary care setting, has recently been applied successfully to the adult IBD population. Following the tenets of the PCMH, this specialty medical home (SMH) emphasizes team-based care that is accessible, comprehensive, patient/family-centered, coordinated, compassionate, and continuous and has demonstrated improved patient outcomes. Children and young adults with IBD have equally complex care needs, with additional challenges not faced by the adult population such as growth, physical and psychosocial development, and transition of care from pediatric to adult providers. Thus, we advocate that the components of the PCMH are equally-if not more-important in caring for the pediatric patient population. In this article, we review what is known about the application of the PCMH model in adult IBD care, describe care delivery within the Center for Pediatric and Adolescent IBD at Nationwide Children's Hospital as an example of a pediatric IBD medical home, and propose a research agenda to further the development and dissemination of comprehensive care delivery for children and adolescents with IBD.

This article summarizes the literature regarding the adult inflammatory bowel disease medical home, highlights the need for similar models in pediatrics using the Nationwide Children's Hospital program as an example, and outlines next steps to support research and development of the pediatric IBD medical home.

Increasing Biosimilar Utilization at a Pediatric Inflammatory Bowel Disease Center and Associated Cost Savings: Show Me the Money.

BACKGROUND: Tumor necrosis factor-alpha inhibitors (anti-TNFs) are a primary treatment for inflammatory bowel disease. Pharmaceutical expenditures and usage of specialty drugs are increasing. In the United States, biosimilars continue to be underutilized, despite opportunities for health care cost savings. Through quality improvement (QI) methodology, we aimed to increase biosimilar utilization among eligible patients initiating intravenous (IV) anti-TNF therapy and describe patient outcomes and associated cost savings. METHODS: Beginning in July 2019, all patients initiating IV anti-TNF therapy were identified and tracked. Using the Institute of Healthcare Improvement Plan-Do-Study-Act cycle, a four-stage problem-solving model used for carrying out change, we trialed interventions to increase biosimilar utilization, including provider, staff, and family education, and utilization of a clinical pharmacist and insurance specialist. Statistical process control charts were used to show improvement over time. Patients' clinical outcome and cost savings were reviewed. RESULTS: Using QI methodology, we increased biosimilar utilization from a baseline of 1% in June 2019 to 96% by February 2021, with sustained improvement. The originator (infliximab) was the insurance company's preferred product for 20 patients (20%). Patient outcomes (IV anti-TNF levels, absence of antidrug antibodies, and physician global assessment) between biosimilars and originators were similar. Estimated cost savings over the project duration were nearly $381,000 (average sales price) and $651,000 (wholesale acquisition cost). CONCLUSIONS: Through QI methodology, we increased biosimilar utilization from 1% to 96% with sustained improvement, without compromising patient outcomes or safety. Estimated cost savings were substantial. Similar methodology could be implemented at other institutions to increase biosimilar utilization and potentially decrease health care costs.

Postcolectomy Enteritis in a Pediatric Patient With Ulcerative Colitis.

Postcolectomy enteritis is characterized by diffuse small bowel inflammatory changes following colectomy for medically refractory ulcerative colitis. Symptoms may include abdominal pain, massive intestinal bleeding, intestinal perforation, and high stoma output. While the exact pathogenesis is unknown, immune dysregulation with increased cytokine and inflammatory cell response is suspected to lead to the inflammatory response. Therefore, immunosuppressive medications are the mainstay for treatment. All cases to date have been described in adult patients. We present a case of postcolectomy enteritis in a pediatric patient who improved without significant intervention.

Applying Telemedicine to Multidisciplinary Pediatric Inflammatory Bowel Disease Care.

Multidisciplinary care is essential to the delivery of comprehensive, whole-person care for children and adolescents with inflammatory bowel disease (IBD). Team members may include medical, psychosocial, and ancillary providers as well as patient and family advocates. There is significant variability in how this care is delivered from center to center, though prior to the COVID-19 pandemic, most care occurred during in-person visits. At the onset of the pandemic, medical systems world-wide were challenged to continue delivering high quality, comprehensive care, requiring many centers to turn to telemedicine technology. The aim of this manuscript is to describe the process by which we converted our multidisciplinary pediatric and adolescent IBD visits to a telemedicine model by leveraging technology, a multidisciplinary team, and quality improvement (QI) methods. Finally, we put our experience into context by summarizing the literature on telemedicine in IBD care, with a focus on pediatrics and multidisciplinary care.

Predicting Suboptimal Transitions in Adolescents With Inflammatory Bowel Disease.

OBJECTIVES: Adolescents and young adults (AYAs) are at risk for disease exacerbations and increased health care utilization around the time of transition to adult care. Our aim was to identify risk factors predictive of a suboptimal transition for AYA with inflammatory bowel disease. MATERIALS AND METHODS: We performed a retrospective chart review of patients with pediatric inflammatory bowel disease transferred to adult care from our institution in 2016 and 2017, recording demographic, psychosocial, and disease-specific data. Post-transfer data were obtained via the health care information exchange from the adult provider within our electronic medical record. We defined suboptimal transition as either a return to pediatric care or requiring care escalation within 1 year of transfer. RESULTS: Out of 104 subjects 37 (36%) were found to have had a suboptimal transition. Our models suggest that a suboptimal transition is associated with several risk factors including any mental health diagnosis (odds ratio [OR] = 4.15; 95% confidence interval [95% CI]: 1.18-14.59), history of medication nonadherence (OR = 5.15 [95% CI: 1.52-17.42]), public insurance (OR = 6.60 [95% CI: 1.25-34.96]), higher Physician Global Assessment score at time of transition (OR = 6.64 [95% CI: 1.60-27.58], and short Pediatric Crohn Disease Activity Index scores (OR = 1.17 [95% CI: 1.03-1.33]). Higher hemoglobin levels at transition were protective (OR = 0.69 [95% CI: 0.48-0.98]). Age at time of transition, disease duration, and medication type at transition were not found to be associated with transition outcomes. CONCLUSION: AYA with public insurance, a mental health history, medication nonadherence, and evidence of active disease may be at greater risk for suboptimal and poor health outcomes at transition.

Improving Post-induction Antitumor Necrosis Factor Therapeutic Drug Monitoring in Pediatric Inflammatory Bowel Disease.

OBJECTIVES: Adequate serum drug levels of tumor necrosis factor-alpha inhibitors (anti-TNF) have been shown to improve outcomes in patients with inflammatory bowel disease. We aim to describe the quality improvement (QI) methods used at our institution to improve post-induction therapeutic drug monitoring (TDM) in children initiating anti-TNF therapy (infliximab and adalimumab) and describe the frequency of subtherapeutic anti-TNF levels. METHODS: Beginning in February 2016, all patients initiating anti-TNF therapy were identified and tracked. Interventions to improve TDM, including the initiation of therapy plans for infliximab, real-time reminders for practitioners, and scheduling modifications for those initiating anti-TNF therapies were implemented using the Institute for Healthcare Improvement Plan-Do-Study-Act cycle approach. Statistical process control charts were used to demonstrate improvement over time. Anti-TNF levels and presence of antidrug antibodies were also recorded. RESULTS: Using QI methodology, we improved post-induction anti-TNF TDM from a baseline of 43% in 2015 to >80% by the end of 2017, with sustained improvement. Infliximab post-induction TDM improved from a baseline of 59% to 82%, whereas adalimumab post-induction TDM improved from baseline of 14% to 79%. In total, 36% of all anti-TNF post-induction levels were <5 µg/mL, with nearly 60% of post-induction infliximab levels being <5 µg/mL. CONCLUSIONS: Through incremental QI approaches, we improved the utilization of anti-TNF post-induction TDM with sustained improvement, approaching our goal of 90%. Subtherapeutic post-induction infliximab levels were common, indicating a strong need for anti-TNF TDM and an opportunity for dose optimization.

A Quality Improvement Approach to External Infliximab Infusions in Pediatric Inflammatory Bowel Disease.

OBJECTIVES: We used a quality improvement (QI) approach to improve access and reduce barriers to care by increasing the number of external infliximab infusions at our pediatric inflammatory bowel disease center. METHODS: Using an iterative QI strategy, pediatric patients ≥12 years of age with inflammatory bowel disease were offered the opportunity to receive infliximab infusions at home/an external infusion center. They were required to first have >5 infusions at the hospital without any significant infusion reactions. Data were collected and tracked monthly using P-charts. Comparisons between control chart centerlines were analyzed using the Fisher exact test. RESULTS: Fifty-four patients received external infusions, 87% had Crohn disease, 63% boys, average age 17.6 ±â€Š2.9 years, and 89% with private insurance. From September 2016 to January 2018, the percentage of eligible patients receiving external infusions was approximately 7%, increasing to approximately 30% by January 2018. A centerline shift, representing a statistically significant change, occurred in October 2016 and June 2017 (P < 0.001). No serious safety concerns have occurred. CONCLUSIONS: Through a multidisciplinary team of stakeholders using QI strategies, we now offer external infusion service options to all appropriate patients as routine practice. Home infusions are a viable option to reduce barriers to care, and our patients did not experience any safety events.

Using Quality Improvement to Increase Utilization of Enteral Therapy in Pediatric Crohn Disease: Results and Outcomes.

INTRODUCTION: Exclusive enteral nutrition (EEN) for induction of remission in children with Crohn disease (CD) is recommended as first-line therapy, but underutilized in the United States related to real and perceived barriers. We hypothesized that quality improvement (QI) methodology could increase use of EEN. METHODS: We developed, implemented, and revised an algorithm and a set of tools to facilitate use of EEN. Through a series of Plan Do Study Act cycles, the approach was modified to overcome provider and patient/family barriers. The primary outcome, the percentage of newly diagnosed CD patients who receive EEN per month between July 2013 and October 2015, assessed using statistical process control. Secondary outcomes, including the short pediatric Crohn disease activity index (sPCDAI), body mass index (BMI) z score, erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), albumin, and hemoglobin were compared before and after EEN. RESULTS: Among patients newly diagnosed with CD, 73 patients initiated EEN and were included (mean age 12.7 ±â€Š2.9 years, 49% girls, 86% white). Rates of utilization of EEN increased significantly from a baseline of <5% to an average of approximately 50%. Of the 73 patients who started EEN, 37 (50%) completed a minimum of 8 weeks. Of those completing therapy, 25 (71%) achieved remission, with a significant reduction of sPCDAI (33.6 ±â€Š14.4 to 10.7 ±â€Š12.3, P < 0.0001) CONCLUSIONS:: Use of QI methodology to systematically implement tools designed to improve utilization was effective in increasing the use of EEN. Among those completing therapy, EEN was effective in inducing remission.

Connecting Families: A Pediatric IBD Center's Development and Implementation of a Volunteer Parent Mentor Program.

It is estimated that over one million people are living with inflammatory bowel disease (IBD) in the United States and that 20-25% of those are children. Pediatric IBD presents with more severe and extensive disease when compared to adults. As with all pediatric chronic illnesses, the patient as well as their parents and siblings are impacted by this diagnosis. Parents often feel afraid, isolated, stressed, angry, guilty, and overwhelmed when their child is diagnosed. Often, there is lack of structured support systems within the healthcare system to meet the complex needs of these families and they are often looking for support outside of the medical setting. Utilization of trained parent mentors as a source of support to newly diagnosed families is one method of addressing these needs. With minimal additional resources, we describe the feasibility of the development and implementation of a volunteer, parent mentoring program that went from an IBD-patient focused program to one that rapidly expanded to a hospital-wide program involving more than 200 mentors matched to over 300 mentees within a 2-year period.