Pursuing Novel Clinical and Research Initiatives in Pediatric IBD
An estimated 20 to 30 percent of patients with inflammatory bowel disease (IBD) are diagnosed during childhood, with the incidence of IBD in children and adolescents continuing to increase. Currently, there are more than 80,000 children in the United States with this diagnosis, which includes Crohn’s disease, ulcerative colitis, and indeterminate colitis.
Robbyn Sockolow, MD, Chief of Pediatric Gastroenterology, Hepatology, and Nutrition at NewYork-Presbyterian Komansky Children’s Hospital, and Neal S. LeLeiko, MD, PhD, Director of the Pediatric IBD Center at NewYork-Presbyterian Morgan Stanley Children’s Hospital, lead major research and clinical programs in pediatric inflammatory bowel disease with a combined caseload of more than 600 children. Their expertise and experience continue to advance the field of this challenging set of gastrointestinal disorders and improve outcomes for this vulnerable population.
Critical Role of Nutrition
The role of nutrition in the management of IBD is a particular interest of Dr. LeLeiko. “It is the basis of almost everything we do in gastroenterology,” says Dr. LeLeiko, who has a rare combination of board certification in pediatric gastroenterology and a PhD in nutritional metabolism and biochemistry. “The importance of incorporating nutritional interventions for treatment of children who lack proper nutrition or to maintain optimal nutrition is well established. However, a definitive role for nutrition as therapy for IBD is only now beginning to emerge.”
In an article published in the March 2020 issue of the Journal of Pediatric Gastroenterology and Nutrition, Dr. LeLeiko, along with his colleagues Joseph A. Picoraro, MD, Associate Director of the Pediatric IBD Center, and Sharon Akabas, PhD, Director, MS in Nutrition, Columbia University’s Institute of Human Nutrition, review the approach necessary to assess the current evidence in support of the use of nutritional therapy in IBD. Their goal is to facilitate informed therapeutic decisions.
“The importance of incorporating nutritional interventions for treatment of children who lack proper nutrition or to maintain optimal nutrition is well established. However, a definitive role for nutrition as therapy for IBD is only now beginning to emerge.” — Dr. Neal S. LeLeiko
“Ongoing data from studies in both experimental models and clinical settings continue to suggest a rationale for nutritional therapy as a component of pediatric IBD treatment,” notes Dr. LeLeiko. “However, it is imperative that any therapeutic diet is investigated with the same rigorous scientific standards used for medical therapies and, furthermore, compared directly to pharmacologic therapies.”
“While research in dietary therapy continues, nutritional care must be part of the overall plan of care for patients with IBD,” adds Dr. Picoraro. “This requires intensive resources, including having a dietitian as a key member of the healthcare team. That’s an important part of our focus.”
Dr. Sockolow agrees. “Today, we are much more proactive when it comes to nutritional health and vitamin and micronutrient status. Families certainly notice how foods affect their child’s symptoms and share that with us and that’s important for us to know and act upon. Staying on top of this can help us catch a flare earlier.”
Addressing Myriad Clinical Concerns in a Multifactorial Disease
Pediatric IBD can be accompanied by a range of extraintestinal manifestations, including anemia and musculoskeletal abnormalities. Pulmonary symptoms can also present in children, but the prevalence is unknown with few studies available to support the frequency or a connection of pulmonary symptoms to IBD disease severity. Dr. Sockolow, Elaine Barfield, MD, pediatric gastroenterologist, and their colleagues at Weill Cornell Medicine, sought to clarify these issues in a study of 159 patients between the ages of 12 and 22 seen in their outpatient pediatric gastroenterology clinic and outpatient infusion center.
Their findings, which were published in the June 2020 issue of Clinical Pediatrics, indicated 9 percent of the patients had pulmonary symptoms, such as cough, sputum production, and shortness of breath, with a small percentage reporting wheeze, and symptoms significantly increased during times of active disease, particularly in Crohn’s disease. The authors note that the study suggests pulmonary manifestations do occur with frequency in patients with IBD and recommend that providers consider inquiring about symptoms, including cough, wheeze, pneumonia, dyspnea, and chest pain, in order to facilitate consultations with pulmonary specialists and intervention when necessary.
Bo Shen, MD, a preeminent expert in interventional IBD worldwide, serves as Section Head and Medical Director for the Adult Inflammatory Bowel Disease Center at NewYork-Presbyerian/Columbia and collaborates with the pediatric IBD program to provide patients from birth to adulthood with a full spectrum of care. Dr. Shen and Dr. Picoraro work closely together to incorporate the latest advances in interventional endoscopy in the management of IBD in children, particularly related to complications, such as stricturing and inflammation, following colectomy or ileal pouch-anal anastomosis surgery.
“Home infusions give patients and their families a welcome degree of flexibility and convenience, allowing those who live in the tri-state area to avoid the traffic, costs, and travails of New York City,” says Dr. Sockolow. “We have made a major push for young IBD patients in the NewYork-Presbyterian system to be able to have home infusions.” Through this program, clinicians now order more than 600 home treatments a year – making it one of the largest such initiatives for pediatric patients in the country.
In 2018, Dr. Barfield and Dr. Sockolow authored a paper published in the April 2018 issue of the Journal of Pediatric Gastroenterology and Nutrition. The article provides eight best practice recommendations developed by a task force of experts from around the country, including Dr. Picoraro from Columbia, to ensure the quality of care for pediatric patients with IBD receiving non-hospital based biologic infusions. The comprehensive clinical report details both patient care considerations and logistical considerations for home- or office-based infusions.
A Seamless Transition to Adult Care
Preparing young patients with IBD for the move from pediatric into adult medicine is a key focus of the pediatric IBD programs. “Adolescents with IBD face unique challenges that can hamper the successful transition from pediatric to adult health care,” says Kimberly A. Chien, MD, a pediatric gastroenterologist in the Pediatric IBD Transition Program at NewYork-Presbyterian Komansky. “Many adolescent IBD patients avoid taking ownership of their disease and allow their parents to oversee their medical management, causing them to feel unprepared as they leave their familiar, sheltered pediatric care environment and navigate unfamiliar adult healthcare terrain.”
“As pediatricians, we take responsibility to properly guide our patients so that they ultimately can be transitioned in a seamless way to the adult world,” says Dr. Sockolow. “Pediatric and adult providers need to communicate closely during the transition. Unlike other specialties, such as cystic fibrosis where adult providers have to have proper handoff and training in the pediatric realm, most adult gastroenterologists haven’t necessarily taken care of adolescent patients or even young adults, which requires a whole different approach.”
“As pediatricians, we take responsibility to properly guide our patients so that they ultimately can be transitioned in a seamless way to the adult world. Pediatric and adult providers need to communicate closely during the transition.” — Dr. Robbyn Sockolow
The conversation regarding transition should begin at about age 14, notes Dr. Sockolow. “Pediatric providers and families need to begin to plan that process and understand what is needed for this particular patient. Some patients are very self-reliant as they grow up, and some need an extra hand,” she says. “If a child is diagnosed while they’re quite young, the parent is naturally very protective of their child. At some point, we have to encourage the parent to enter into this process and trust that their child will ultimately be able to take care of themselves.”
“After meeting the adult provider, our team will follow up with the patient at a return pediatric GI visit so we can learn how they are doing and how their first experience was with the adult gastroenterologist,” adds Dr. Chien. “It’s always extremely rewarding to learn that these patients are thriving and are applying the skills they learned while in the program.”
A Comprehensive Research Agenda
IBD in children and adolescents presents a number of challenges distinct from adults with colitis or Crohn’s disease, most notably limited therapeutic options; delayed access to new therapies available to adult patients; and the scarcity of large-scale pediatric trials. In 2018, Dr. Picoraro served on the working group of the Pediatric Resource Organization for Kids with Inflammatory Intestinal Diseases (PRO-KIIDS) Clinical Innovations Meeting, which was called to identify priorities and develop a plan for advancing the care of children with IBD. The PRO-KIIDS network helped establish a foundation for pediatric IBD research with a focus on accelerating therapies for children. Their initiatives are presented in the January 1, 2019 issue of Inflammatory Bowel Diseases.
Clinicians and scientists at Columbia and Weill Cornell Medicine specializing in pediatric IBD pursue studies that span from investigations of biologic origins to identifying novel therapeutics.
IBD Tissue Bank
Through collaboration with the Jill Roberts Institute for Research in Inflammatory Bowel Disease at Weill Cornell Medicine, Dr. Sockolow and her faculty have access to tremendous resources and renowned IBD researchers in adult IBD. This relationship enabled the creation of the nation’s first live-cell pediatric IBD tissue bank. The repository, which now contains samples of blood and tissue biopsies from more than 700 patients, enables researchers to provide deeper insight into disease subtypes and how best to treat them.
Helping Mucosal Healing
In a study published in the April 2020 issue of Science, researchers in the Jill Roberts Institute describe how the protein hepcidin, which helps the body regulate iron metabolism, plays a critical role in the ability of the intestines to repair injury to the mucosa. Conducting experiments in a wild-type and hepcidin-deficient mouse model of intestinal tissue damage, inflammation, and repair, the research team showed conventional dendritic cells produce hepcidin in response to microbiota-derived signals, which subsequently limits iron release from intestinal phagocytes. This prevents tissue infiltration by the microbiota, and, as a result, promotes mucosal healing. The authors further note that the results indicate that “hepcidin mimetics could be a beneficial therapeutic strategy in the context of fecal microbiota transplan or gastrointestinal diseases where mucosal healing is an emerging therapeutic goal.”
Immunopathogenesis of IBD
Pathogenesis of inflammatory bowel disease has been shown to involve a number of factors related to the immune system, environment, and in particular, alterations in the gut microbiome. Dr. LeLeiko helped to lead a large-scale study that has identified IgA coating of specific gut microbiota in a clinically well-defined cohort of IBD patients – the Ocean State Crohn’s and Colitis Area Registry. The results of the study, published in the January 13, 2021 issue of Cell Host & Microbe, demonstrated that “consideration of host immune response to specific bacteria reveals unique, potentially disease-modifying taxa, as well as potential biomarkers for disease progression...and may thus provide a framework for the development of more refined biomarkers of disease course and direct future microbial-based therapeutic approaches.”
A New Inflammatory Pathway
Interleukin (IL)-2 is a cytokine necessary to prevent chronic inflammation in the gastrointestinal tract and its protective effects involve the generation, maintenance, and function of regulatory T cells. Researchers in the Jill Roberts Institute showed that IL-2 is predominantly produced by group-3 innate lymphoid cells (ILC3s). This production was found to be significantly reduced in the small intestines of patients with Crohn’s disease. Results from the study, which were reported in the April 18, 2019 issue of Nature, identify a novel pathway of immune regulation that uniquely occurs in the healthy small intestine; will inform ongoing strategies of therapeutically administering low-dose IL-2 to IBD patients; substantially advance the understanding of the role and regulation of IL-2 throughout the gastrointestinal tract; and critically identify a previously unappreciated direct communication between ILC3 and regulatory T cells.
Clinical Care with a Healthy Dose of Compassion
When caring for a child with IBD, management by NewYork-Presbyterian’s IBD specialists is over and above the clinical components of diagnosis and treatment. These physicians, nurse practitioners, dietitians, social workers, and other subspecialists come together to address how the condition affects the child or adolescent, their schooling, emotional health, and overall quality of life, as well as the parents and their needs in coping with the oftentimes complex issues that accompany the diagnosis of IBD. It is why physicians refer and parents so often turn to them for care.
“I will have done my job well if the only time my patients remember they have IBD is when they get their medication,” says Dr. Sockolow.
Dr. LeLeiko agrees. “If there is one thing that I would want us to be known for, it is for being kind to our patients.”
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