Browsing by Author "Peterson, Kathryn"

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    Development of a Core Outcome Set for Therapeutic Studies in Eosinophilic Esophagitis (COREOS)
    (Elsevier, 2021) Ma, Christopher; Schoepfer, Alain M.; Dellon, Evan S.; Bredenoord, Albert J.; Chehade, Mirna; Collins, Margaret H.; Feagan, Brian G.; Furuta, Glenn T.; Gupta, Sandeep K.; Hirano, Ikuo; Jairath, Vipul; Katzka, David A.; Pai, Rish K.; Rothenberg, Marc E.; Straumann, Alex; Aceves, Seema S.; Alexander, Jeffrey A.; Arva, Nicoleta C.; Atkins, Dan; Biedermann, Luc; Blanchard, Carine; Cianferoni, Antonella; Ciriza de los Rios, Constanza; Clayton, Frederic; Davis, Carla M.; de Bortoli, Nicola; Dias, Jorge A.; Falk, Gary W.; Genta, Robert M.; Ghaffari, Gisoo; Gonsalves, Nirmala; Greuter, Thomas; Hopp, Russell; Hsu Blatman, Karen S.; Jensen, Elizabeth T.; Johnston, Doug; Kagalwalla, Amir F.; Larsson, Helen M.; Leung, John; Louis, Hubert; Masterson, Joanne C.; Menard-Katcher, Calies; Menard-Katcher, Paul A.; Moawad, Fouad J.; Muir, Amanda B.; Mukkada, Vincent A.; Penagini, Roberto; Pesek, Robert D.; Peterson, Kathryn; Putnam, Philip E.; Ravelli, Alberto; Savarino, Edoardo V.; Schlag, Christoph; Schreiner, Philipp; Simon, Dagmar; Smyrk, Thomas C.; Spergel, Jonathan M.; Taft, Tiffany H.; Terreehorst, Ingrid; Vanuytsel, Tim; Venter, Carina; Vieira, Mario C.; Vieth, Michael; Vlieg-Boerstra, Berber; von Arnim, Ulrike; Walker, Marjorie M.; Wechsler, Joshua B.; Woodland, Philip; Woosley, John T.; Yang, Guang-Yu; Zevit, Noam; Safroneeva, Ekaterina; Medicine, School of Medicine
    Background End points used to determine treatment efficacy in eosinophilic esophagitis (EoE) have evolved over time. With multiple novel therapies in development for EoE, harmonization of outcomes measures will facilitate evidence synthesis and appraisal when comparing different treatments. Objective We sought to develop a core outcome set (COS) for controlled and observational studies of pharmacologic and diet interventions in adult and pediatric patients with EoE. Methods Candidate outcomes were generated from systematic literature reviews and patient engagement interviews and surveys. Consensus was established using an iterative Delphi process, with items voted on using a 9-point Likert scale and with feedback from other participants to allow score refinement. Consensus meetings were held to ratify the outcome domains of importance and the core outcome measures. Stakeholders were recruited internationally and included adult and pediatric gastroenterologists, allergists, dieticians, pathologists, psychologists, researchers, and methodologists. Results The COS consists of 4 outcome domains for controlled and observational studies: histopathology, endoscopy, patient-reported symptoms, and EoE-specific quality of life. A total of 69 stakeholders (response rate 95.8%) prioritized 42 outcomes in a 2-round Delphi process, and the final ratification meeting generated consensus on 33 outcome measures. These included measurement of the peak eosinophil count, Eosinophilic Esophagitis Histology Scoring System, Eosinophilic Esophagitis Endoscopic Reference Score, and patient-reported measures of dysphagia and quality of life. Conclusions This interdisciplinary collaboration involving global stakeholders has produced a COS that can be applied to adult and pediatric studies of pharmacologic and diet therapies for EoE and will facilitate meaningful treatment comparisons and improve the quality of data synthesis.
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    Impressions and aspirations from the FDA GREAT VI Workshop on Eosinophilic Gastrointestinal Disorders Beyond Eosinophilic Esophagitis and Perspectives for Progress in the Field
    (Elsevier, 2022) Rothenberg, Marc E.; Hottinger, Shawna K. B.; Gonsalves, Nirmala; Furuta, Glenn T.; Collins, Margaret H.; Talley, Nicholas J.; Peterson, Kathryn; Menard-Katcher, Calies; Smith, Macie; Hirano, Ikuo; Genta, Robert M.; Chehade, Mirna; Gupta, Sandeep K.; Spergel, Jonathan M.; Aceves, Seema S.; Dellon, Evan S.; Pediatrics, School of Medicine
    The US Food and Drug Administration hosted a workshop on July 21, 2021, to discuss the disease characteristics, natural history, and end points to assess treatment benefit in patients with eosinophilic gastrointestinal disorders (EGIDs) beyond eosinophilic esophagitis (EoE). Notably, EGIDs beyond EoE, such as eosinophilic gastritis, eosinophilic enteritis, and eosinophilic colitis, herein referred to as non-EoE EGIDs, are understudied relative to EoE. This workshop provided a forum for open discussion among stakeholders-medical professionals (including their societies and research groups), Food and Drug Administration representatives, an industry representative, and a patient representative-to facilitate drug development. Experts in many disciplines related to EGIDs, including allergy, immunology, epidemiology, gastroenterology, and pathology, and both adult and pediatric clinicians contributed. Herein, we discuss some of the insights of the material presented at the meeting and present perspectives on moving the field forward toward drug approval.
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    Mucosal Microbiota Associated With Eosinophilic Esophagitis and Eosinophilic Gastritis
    (Wiley, 2023) Furuta, Glenn T.; Fillon, Sophie A.; Williamson, Kayla M.; Robertson, Charles E.; Stevens, Mark J.; Aceves, Seema S.; Arva, Nicoleta C.; Chehade, Mirna; Collins, Margaret H.; Davis, Carla M.; Dellon, Evan S.; Falk, Gary W.; Gonsalves, Nirmala; Gupta, Sandeep K.; Hirano, Ikuo; Khoury, Paneez; Leung, John; Martin, Lisa J.; Menard-Katcher, Paul; Mukkada, Vincent A.; Peterson, Kathryn; Spergel, Jonathan M.; Wechsler, Joshua B.; Yang, Guang-Yu; Rothenberg, Marc E.; Harris, J. Kirk; Pediatrics, School of Medicine
    Objective: The aim of the study was to determine the mucosal microbiota associated with eosinophilic esophagitis (EoE) and eosinophilic gastritis (EoG) in a geographically diverse cohort of patients compared to controls. Methods: We conducted a prospective study of individuals with eosinophilic gastrointestinal disease (EGID) in the Consortium of Eosinophilic Gastrointestinal Disease Researchers, including pediatric and adult tertiary care centers. Eligible individuals had clinical data, mucosal biopsies, and stool collected. Total bacterial load was determined from mucosal biopsy samples by quantitative polymerase chain reaction (PCR). Community composition was determined by small subunit rRNA gene amplicons. Results: One hundred thirty-nine mucosal biopsies were evaluated corresponding to 93 EoE, 17 EoG, and 29 control specimens (18 esophageal) from 10 sites across the United States. Dominant community members across disease activity differed significantly. When comparing EoE and EoG with controls, the dominant taxa in individuals with EGIDs was increased ( Streptococcus in esophagus; Prevotella in stomach). Specific taxa were associated with active disease for both EoE ( Streptococcus , Gemella ) and EoG ( Leptotrichia ), although highly individualized communities likely impacted statistical testing. Alpha diversity metrics were similar across groups, but with high variability among individuals. Stool analyses did not correlate with bacterial communities found in mucosal biopsy samples and was similar in patients and controls. Conclusions: Dominant community members ( Streptococcus for EoE, Prevotella for EoG) were different in the mucosal biopsies but not stool of individuals with EGIDs compared to controls; taxa associated with EGIDs were highly variable across individuals. Further study is needed to determine if therapeutic interventions contribute to the observed community differences.
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    Prospective Endoscopic Activity Assessment for Eosinophilic Gastritis in a Multisite Cohort
    (Wolters Kluwer, 2022) Hirano, Ikuo; Collins, Margaret H.; King, Eileen; Sun, Qin; Chehade, Mirna; Abonia, J. Pablo; Bonis, Peter A.; Capocelli, Kelly E.; Dellon, Evan S.; Falk, Gary W.; Gonsalves, Nirmala; Gupta, Sandeep K.; Leung, John; Katzka, David; Menard-Katcher, Paul; Khoury, Paneez; Klion, Amy; Mukkada, Vincent A.; Peterson, Kathryn; Shoda, Tetsuo; Rudman-Spergel, Amanda K.; Spergel, Jonathan A.; Yang, Guang-Yu; Rothenberg, Marc E.; Aceves, Seema S.; Furuta, Glenn T.; CEGIR investigators; Pediatrics, School of Medicine
    Introduction: Eosinophilic gastritis (EG) is a chronic inflammatory disease of the stomach characterized by eosinophil-predominant gastric mucosal inflammation and gastrointestinal symptoms. The aim of this study was to prospectively evaluate endoscopic features in a large series of children and adults with EG to better understand the endoscopic manifestations and develop a standardized instrument for investigations. Methods: Data were prospectively collected as part of the Consortium for Eosinophilic Gastrointestinal Disease Researchers, a national collaborative network. Endoscopic features were prospectively recorded using a system specifically developed for EG, the EG Endoscopic Reference System (EG-REFS). Correlations were made between EG-REFS and clinical and histologic features. Results: Of 98 patients with EG, 65 underwent assessments using EG-REFS. The most common findings were erythema (72%), raised lesions (49%), erosions (46%), and granularity (35%); only 8% of patients with active histology (≥30 eosinophils/high-power field) exhibited no endoscopic findings. A strong correlation between EG-REFS scores and physician global assessment of endoscopy severity was demonstrated (Spearman r = 0.84, P < 0.0001). The overall score and specific components of EG-REFS were more common in the antrum than in the fundus or body. EG-REFS severity was significantly correlated with active histology, defined by a threshold of ≥30 eosinophils/high-power field (P = 0.0002). Discussion: Prospective application of EG-REFS identified gastric features with a strong correlation with physician global assessment of endoscopic activity in EG. Endoscopic features demonstrated greater severity in patients with active histology and a predilection for the gastric antrum. Further development of EG-REFS should improve its utility in clinical studies.
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    Reliability and Responsiveness of Endoscopic Disease Activity Assessment in Eosinophilic Esophagitis
    (Elsevier, 2022) Ma, Christopher; Bredenoord, Albert J.; Dellon, Evan S.; Alexander, Jeffrey A.; Biedermann, Luc; Hogan, Malcolm; Guizzetti, Leonardo; Zou, Guangyong; Katzka, David A.; Chehade, Mirna; Falk, Gary W.; Furuta, Glenn T.; Gupta, Sandeep K.; Kagalwalla, Amir F.; Schoepfer, Alain M.; Miehlke, Stephan; Moawad, Fouad J.; Peterson, Kathryn; Gonsalves, Nirmala P.; Straumann, Alex; Wechsler, Joshua B.; Rémillard, Julie; Shackelton, Lisa M.; Almonte, Hector S.; Feagan, Brian G.; Jairath, Vipul; Hirano, Ikuo; Pediatrics, School of Medicine
    Background and Aims Endoscopic outcomes have become important measures of eosinophilic esophagitis (EoE) disease activity, including as an endpoint in randomized controlled trials (RCTs). We evaluated the operating properties of endoscopic measures for use in EoE RCTs. Methods Modified Research and Development/University of California Los Angeles (RAND/UCLA) appropriateness methods and a panel of 15 international EoE experts identified endoscopic items/definitions with face validity, which were used in a 2-round voting process to define simplified (all items graded absent/present) and expanded versions (additional grades for edema, furrows, and/or exudates) of the EoE Endoscopic Reference Score (EREFS). Inter- and intra-rater reliability of these instruments (expressed as intraclass correlation coefficients [ICC]), were evaluated using paired endoscopy video assessments of two blinded central readers before and after 8 weeks of proton pump inhibitors, swallowed topical corticosteroids, or dietary elimination. Responsiveness was measured using the standardized effect size (SES). Results The appropriateness of 41 statements relevant to EoE endoscopic activity (endoscopic items, item definitions/grading, and other considerations relevant for endoscopy) was considered. The original and expanded EREFS demonstrated moderate-to-substantial inter-rater reliability (ICCs 0.472-0.736, and 0.469-0.763, respectively) and moderate-to-almost perfect intra-rater reliability (ICCs 0.580-0.828, and 0.581-0.828, respectively). Strictures were least reliably assessed (ICCs 0.072-0.385). The original EREFS was highly responsive (SES 1.126 [95% CI 0.757, 1.534]), although both expanded versions of EREFS, scored based on worst affected area, were numerically most responsive to treatment (expanded furrows, SES 1.229 [95% CI: 0.858, 1.643]; all items expanded, SES 1.252 [95% CI: 0.880, 1.667]). The EREFS and its modifications were not more reliably scored by segment, and also not more responsive when proximal and distal EREFS scores were summed. Conclusions EREFS and its modifications were reliable and responsive, and the original or expanded versions of the EREFS may be preferred in RCTs. Disease activity scored based on the worst affected area optimizes reliability and responsiveness.