Operating Properties of Disease Activity Indices in Pediatric Inflammatory Bowel Disease: A Systematic Review.

Background: Accurate, reliable, and responsive disease activity indices are important to streamline drug approval and treatment modalities for pediatric inflammatory bowel disease (pIBD). We aimed to identify all scoring indices used in pIBD randomized controlled trials (RCTs) and to evaluate their operating properties.

Methods: MEDLINE, EMBASE, and CENTRAL were searched on December 6, 2022, to identify studies evaluating clinical, endoscopic, imaging, or patient-reported outcome measures (PROMs) in pIBD including Crohn's disease (CD) and ulcerative colitis (UC).

Infliximab Monotherapy vs Combination Therapy for Pediatric Crohn's Disease Exhibit Similar Pharmacokinetics.

Background: The use of concomitant azathioprine may improve efficacy and pharmacokinetic (PK) properties of infliximab (IFX) but is also associated with an increased risk of adverse events. Proactive therapeutic drug monitoring (pTDM) of IFX monotherapy is an alternative strategy to improve PK. The aim of this study was to evaluate whether IFX with an immunomodulator (combo) has PK benefits over IFX-pTDM (mono) in pediatric Crohn's disease (CD).

HLA-DQA1∗05 Genotype and Immunogenicity to Tumor Necrosis Factor-α Antagonists: A Systematic Review and Meta-analysis.

Background & Aims: Identifying patients at high risk of immunogenicity is important when selecting tumor necrosis factor (TNF)-α antagonists in patients with immune-mediated inflammatory diseases (IMIDs). We evaluated the association HLA-DQA1∗05 genotype and risk of immunogenicity with TNF-α antagonists.

Methods: Through a systematic review through July 14, 2022, we identified studies in patients with IMIDs treated with TNF-α antagonists, which reported the risk of immunogenicity and/or secondary loss of response in patients with HLA-DQA1∗05 variants.

Real world population pharmacokinetic study in children and young adults with inflammatory bowel disease discovers novel blood and stool microbial predictors of vedolizumab clearance.

Background: Vedolizumab for inflammatory bowel disease (IBD) is often intensified based on distinct pharmacokinetics in children. Prior adult-specific population pharmacokinetic models have identified limited covariates of drug clearance.

Aims: To establish a population pharmacokinetic model for children and young adults to identify novel covariates of drug clearance to better account for paediatric-specific inter-patient variability in vedolizumab pharmacokinetics; a key secondary exploratory aim was to identify microbial signatures of pharmacokinetic outcomes in a subset of patients.

Antibodies-to-infliximab accelerate clearance while dose intensification reverses immunogenicity and recaptures clinical response in paediatric Crohn's disease.

Background: Antibodies to infliximab (ATI) are associated with secondary loss of response and increased risk for drug reactions. Limited studies have associated ATI with increased infliximab clearance.

Aims: We assessed the impact of ATI on infliximab clearance and loss of response in an inception paediatric Crohn's disease cohort with 1-year follow-up.

Predicting Therapeutic Response in Pediatric Ulcerative Colitis-A Journey Towards Precision Medicine.

Ulcerative colitis (UC) is a disabling disease, characterized by chronic inflammation of the colon, with a rising prevalence worldwide in the pediatric age group. Although UC presents in children with varying severity, disease extent, and comorbidities, initial treatment is essentially uniform, consisting of 5-aminosalicylate drugs with corticosteroid induction for those with moderately to severely active disease. With the advent of anti-tumor necrosis factor (TNF) biologic therapy and several new biologics and small-molecule drugs for UC, precision medicine approaches to treatment are needed to more rapidly achieve sustained remission, restore quality of life, normalize development, and limit exposure to toxic corticosteroids in children with UC.

Achieving Target Infliximab Drug Concentrations Improves Blood and Fecal Neutrophil Biomarkers in Crohn's Disease.

Background: The neutrophil fecal biomarkers, calprotectin (FCP) and lactoferrin (LCT), and peripheral blood neutrophil CD64 surface receptor (nCD64) are biomarkers for mucosal inflammation in inflammatory bowel disease (IBD). Although FCP has been evaluated as a biomarker for mucosal healing, cut points for LCT and nCD64 are less known. We aimed to identify the cut points for LCT and nCD64 that were associated with FCP remission, with a secondary aim to evaluate the relationship between biochemical outcomes and infliximab (IFX) trough concentrations.

Favorable Outcomes and Anti-TNF Durability After Addition of an Immunomodulator for Anti-Drug Antibodies in Pediatric IBD Patients.

Background: Anti-drug antibodies (ADAs) to anti-tumor necrosis factor alpha (anti-TNF) drugs are associated with increased drug clearance and loss of response. We aimed to assess the effectiveness of starting an immunomodulator (IM) drug in patients with newly detected ADAs on anti-TNF monotherapy.

Methods: We reviewed the medical records of pediatric patients with inflammatory bowel disease on infliximab or adalimumab monotherapy with first-time detection of significant ADAs between 2014 and 2018.

Upper Gastrointestinal Endoscopy in Adolescents With Severe Obesity Before Vertical Sleeve Gastrectomy.

Objectives: Esophagogastroduodenoscopy (EGD) is often performed to evaluate for mucosal and anatomical abnormalities before vertical sleeve gastrectomy (SG). Little is known, however, about how prebariatric EGD in adolescents influences clinical management or outcome. Our aim was to assess if an abnormal prebariatric EGD resulted in interventions or modification of bariatric surgery.

Prevalence of functional GI disorders among pediatric patients with persistent asthma.

Objective: Functional gastrointestinal (GI) disorders (FGIDs), such as irritable bowel syndrome, functional abdominal pain and dyspepsia, are common causes of chronic GI symptoms in children. Prior studies found high comorbidity of FGID and asthma. This study aimed to assess the prevalence and comorbidities of FGID among pediatric patients with asthma at a university-affiliated urban community hospital.

Efficacy and Follow-up of Segmental or Subtotal Colectomy in Patients With Colitis-Associated Neoplasia.

The historical approach to neoplasia in the setting of chronic colitis was to perform a total proctocolectomy. Recent consensus and society guidelines suggest that when dysplastic lesions can be removed endoscopically, continued surveillance is appropriate. This is based on improvements in optical technologies and the low risk of metachronous colorectal carcinoma in these patients.

Safety and Efficacy of Combination Treatment With Calcineurin Inhibitors and Vedolizumab in Patients With Refractory Inflammatory Bowel Disease.

Background & Aims: Little is known about the efficacy and safety of induction therapy with calcineurin inhibitors in combination with vedolizumab for patients with Crohn's disease (CD) or ulcerative colitis (UC). We analyzed the outcomes of patients receiving vedolizumab along with calcineurin inhibitors.

Methods: We collected data on patients with CD (n = 9) or UC (n = 11) who began treatment with vedolizumab from May 20, 2014, through March 30, 2015, and received calcineurin inhibitors (tacrolimus or cyclosporin) during the first 12 months of vedolizumab therapy.

Methotrexate for the Treatment of Pediatric Crohn's Disease: A Systematic Review and Meta-analysis.

Background: Methotrexate (MTX) is an immunomodulator used for the treatment of pediatric inflammatory bowel disease (IBD). There are currently no RCTs that assess the treatment efficacy of methotrexate within the pediatric IBD patient population. This systematic review and meta-analysis assesses the efficacy of MTX therapy among the existing pediatric literature.

Vedolizumab as Induction and Maintenance for Inflammatory Bowel Disease: 12-month Effectiveness and Safety.

Background: Vedolizumab is approved for moderate to severe Crohn's disease (CD) and ulcerative colitis (UC). We present prospective, 1-year data of the real-world effectiveness and safety of vedolizumab in inflammatory bowel disease.

Methods: Consecutive patients receiving vedolizumab for treatment of UC or CD with at least 14 weeks of follow-up, regardless of outcome, were included.

Histological inflammation increases the risk of colorectal neoplasia in ulcerative colitis: a systematic review.

Background/aims: Ulcerative colitis (UC) patients are at greater risk for the development of colorectal neoplasia. Several individual studies have demonstrated associations between severity of histologic inflammation and colorectal neoplasia. However, a comprehensive systematic review has not been completed.

Surveillance of IBD Using High Definition Colonoscopes Does Not Miss Adenocarcinoma in Patients with Low-grade Dysplasia.

Background: Historically, limits to the ability to detect dysplasia in chronic inflammatory bowel disease (IBD)-associated colitis resulted in the recommendation that neoplasia of any grade be treated by proctocolectomy. We hypothesized that with improved optical technologies, most neoplasia in colitis is now detectable and reassessed the prevalence of colitis-associated neoplasia.

Methods: We retrospectively reviewed all our patients with IBD who had pathologist-confirmed neoplasia on surveillance colonoscopy and underwent a subsequent colectomy.

Successful Treatment of Ulcerative Colitis With Vedolizumab in a Patient With an Infliximab-Associated Psoriasiform Rash.

Psoriatic skin lesions associated with anti-tumor necrosis factor (TNF) agents are well-described in the medical literature. However, the etiology and optimal management of this condition remain unclear. Vedolizumab is a novel, gut-specific, anti-integrin agent used for the treatment of inflammatory bowel disease (IBD).

[Crohn's disease: a controversy].

In 1932, the New York City-based gastroenterologist, Burril B. Crohn, published the manuscript 'Regional Ileitis' in The Journal of the American Medical Association (JAMA). This publication is responsible for the current designation of Crohn's disease.

Optimal doses of methotrexate combined with anti-TNF therapy to maintain clinical remission in inflammatory bowel disease.

Background And Aims: Methotrexate (MTX) is sometimes used as part of combination therapy for the treatment of inflammatory bowel disease [IBD]; however, the optimal MTX dose for combination therapy has not been established. This study compared the efficacy of lower-dose and higher-dose MTX with anti tumor necrosis factor alpha (anti-TNF) therapy among IBD patients.

Methods: Retrospective chart review was performed of 88 IBD patients at our center between 2010 and 2013.

Fecal microbiota transplantation as therapy for inflammatory bowel disease: a systematic review and meta-analysis.

Background And Aims: Fecal microbiota transplantation (FMT) has gained interest as a novel treatment option for inflammatory bowel diseases (IBD). While publications describing FMT as therapy for IBD have more than doubled since 2012, research that investigates FMT treatment efficacy has been scarce. We conducted a systematic review and meta-analysis to evaluate the efficacy of FMT as treatment for patients with IBD.

Agreement between patient- and physician-completed Pediatric Ulcerative Colitis Activity Index scores.

Objectives: Currently validated ulcerative colitis (UC) activity measures are physician based, but incorporate patient reports of symptoms. We aimed to assess whether patient-completed Pediatric UC Activity Index (PUCAI) scores are comparable to those of physician scores.

Patients And Methods: We performed a single-center prospective study to assess agreement between patient- and physician-completed PUCAI scores.