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Biologic Treatment of Pediatric Inflammatory Bowel Disease

A Decade of JPGN Contributions
9781975123574
ISBN/ISSN
9781975123574
Publication Date
January 31, 2019
2019-01-31
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9781975123574
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  • Description
    Drug development in children and adolescents occasionally is hindered by a hesitance to expose young patients to experimental and untested therapies. A case in point is the application of biologic agents in the management of pediatric patients with inflammatory bowel disease (IBD). The degree of acceptance of antitumor necrosis factor (TNF) agents after their introduction as a novel treatment option has ranged from initial enthusiasm to caution resulting from fear of complications such as hepatosplenic T-cell lymphoma (HSTCL) to approval as part of standard management. In fact, as we gather additional experience and evidence, a trend toward the use of biologic agents as a first-line treatment has emerged.
    For this introductory e-book, we selected articles from JPGN that represent seminal work on the application, safety, and efficacy of the 2 leading anti-TNF agents, infliximab and adalimumab, in the treatment of pediatric patients with chronic IBD. Several NASPGHAN and ESPGHAN clinical research articles document the role of these medications in the management of specific patients with complicated IBD. We also present several notable case reports, including one of the first documented cases of HSTCL (Thayu et al).
    Anti-TNF medications were aimed at initially Crohn disease, following postulated involvement of TNF in T-helper cell 1 disorders. The excitement overanti-TNF therapy in Crohn disease was stimulated in particular by emerging evidence that mucosal healing could be achieved for the first time. Extending the application of anti-TNF agents in IBD, Mamula and colleagues’ article reported the successful application of infliximab in pediatric patients with ulcerative colitis, with a corresponding review by Fuss.
    Early enthusiasm for infliximab therapy waned in light of reports of an association between anti-TNF therapy and the development of HSTCL. JPGN published one of the first cases in 2005, and the Food and Drug Administration’s Adverse Event Reporting System followed with several case reports of this association. In 2006, the Food and Drug Administration mandated a black box warning directed at anti-TNF agents. Subsequent evidence has implicated immunomodulator agents, primarily azathioprine and mercaptopurine, rather than anti-TNF agents, in this rare but serious complication. Nevertheless, apprehension that anti-TNF agents may induce HSTCL has been slow to dissipate, and several longitudinal surveillance studies have been launched to address this issue.
    deRidder et al documented the advantages of repeated dosing rather than intermittent or “as needed” application of anti-TNF agents. The accompanying editorial by F.M. Ruemmele discussed the findings of deRidder et al and their potential complications, including infections and 1 fatality presumed to have been the result of sepsis. Newer research has further documented the efficacy of infliximab, with a few additional reports about HSTCL. Reports by Ruemmele et al, followed by Wynands et al, and, most recently, by Nuti et al, document the safety and efficacy of repeated infusions of anti-TNF therapies. In addition, previous work by Miele et al showed that human anti-chimeric antibody formation associated with infusion reactions could be tempered with the concomitant use of immunomodulators. Although pediatric gastroenterologists agree in general on dosing schedules, other practitioners (Adler et al) continue to use a variety of dosing regimens. As noted by Falaive et al, the commonly applied dosage regimens may be inadequate for patients with severe ulcerative or Crohn colitis.
    The complexity of the immune system is evidenced by paradoxical reports implicating anti-TNF agents in the development of diseases that are typically treated with these medications. In addition to the well-recognized complication of psoriasis, development of Crohn disease in a patient treated with etanercept for juvenile idiopathic arthritis (Ruemmele et al) is documented in this series of articles.
    The need for more data on the natural history of IBD in childhood was highlighted by Hyams and Markowitz in their 2005 review and followed by other reports. These articles, including several reproduced in this e-book, have laid the groundwork for new clinical trials. The Crohn’s and Colitis Foundation of America, along with the National Institutes of Health and other funding sources, have taken an important lead in supporting multinational projects designed to explore these issues.
    NASPGHAN and ESPGHAN have issued clinical observations and guidelines for pediatric IBD. Two publications included here (Pfefferkorn et al and de Zoeten et al) suggest using biologic agents as treatment regimens in pediatric patients with IBD.
    It is hoped that this collection of research papers, case reports, and critical reviews will assist our readers in considering treatment options and further advances in the care of young patients with chronic IBD.
  • Specs
    ISBN/ISSN
    9781975123574
    Product Format
    VST ePub3
    Publication Date
    January 31, 2019
  • Melvin B. Heyman MD, MPH
    Raanan Shamir
  • Table of contents
    Introduction
    Treatment of Ulcerative Colitis with Infliximab: Are We There Yet?
    IJ Fuss
    Infliximab in Pediatric Ulcerative Colitis: Two-Year Follow-up
    P. Mamula, JE Markowitz, LI Cohen, et al
    Human Antichimeric Antibody in Children and Young Adults with Inflammatory Bowel Disease Receiving Infliximab
    E Miele, JE Markowitz, P Mamula, et al
    Infliximab: How to Use It in Pediatric Crohn's Disease
    FM Ruemmele
    Infliximab Therapy in 30 Patients with Refractory Pediatric Crohn Disease with and without Fistulas in the Netherlands
    L de Ridder, JC Escher, J Bouquet, et al

    Development of Crohn Disease During Anti-TNF-a Therapy in a Child with Juvenile Idiopathic Arthritis
    FM Ruemmele, A-M Prieur, C Talbotec, et al
    Safety of Infliximab Treatment in Pediatric Patients with Inflammatory Bowel Disease
    CA Friesen, C Calabro, K Christensen, et al
    Hepatosplenic T-Cell Lymphoma in an Adolescent Patient After Immunomodulator and Biologic Therapy for Crohn DIsease
    M Thayu, JE Markowitz, P Mamula, et al
    Can We Alter the Natural History of Crohn Disease in Children?
    JS Hyams and JF Markowitz
    Infliximab Dependency in a National Cohort of Children with Crohn's Disease
    V Wewer, L Riis, I Vind, et al
    Infliximab in Pediatric Crohn Disease Patients with Enterovesicular Fistulas
    JE Teitelbaum, S Saeed, M Triantafyllopoulou, et al
    Infliximab Use in Children and Adolescents with Inflammatory Bowel Disease
    L de Ridder, MA Benninga, JAJM Taminiau, et al
    12-Month Follow-up after Successful Infliximab Therapy in Pediatric Crohn Disease
    J Wynands, R Belbouab, S Candon, et al
    Safety and Efficacy of Adalimumab in Pediatric Patients with Crohn Disease
    MJ Wyneski, A Green, M Kay, et al
    Pediatric Inflammatory Bowel Diseases and the Risk of Lymphoma: Should We Revise our Treatment Strategies?
    S Cucchiara, JC Escher, H Hildebrand, et al
    Hepatosplenic T Cell Lymphoma Associated with Infliximab Use in Young Patients Treated for Inflammatory Bowel Disease: Update
    AC Mackey, L Green, C Leptak, et al
    Drug-Induced Lupus Associated with Infliximab and Adalimumab in an Adolescent with Crohn Disease
    GC Zella, ME Weinblatt, HS Winter
    Medication Knowledge: An Initial Step in Self-Management for Youth with Inflammatory Bowel Disease
    LN Fishman, D Houtman, J van Groningen, et al
    Variation in Infliximab Administration Practices in the Treatment of Pediatric Inflammatory Bowel Disease
    J Adler, KC Sandberg, BH Shpeen, et al
    NASPGHAN Clinical Report on the Evaluation and Treatment of Pediatric Patients with Internal Penetrating Crohn Disease: Intraabdominal Abscess with and without Fistula
    MD Pfefferkorn, FE Marshalleck, SA Saeed, et al
    Diagnosis and Treatment of Perianal Crohn Disease: NASPGHAN Clinical Report and Consensus Statement
    EF de Zoeten, BA Pasternak, P Mattei, et al
    Outcomes Following Infliximab Therapy for Pediatric Patients Hospitalized with Refractory Colitis-Predominant IBD
    TO Falaiye, KR Mitchell, Z Lu, et al
    Biological Therapy in a Pediatric Crohn's Disease Population Followed at a Referral Center
    F Nuti, F Viola, F Civitelli, et al
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