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Item A Clinical Severity Index for Eosinophilic Esophagitis: Development, Consensus, and Future Directions(Elsevier, 2022) Dellon, Evan S.; Khoury, Paneez; Muir, Amanda B.; Liacouras, Chris A.; Safroneeva, Ekaterina; Atkins, Dan; Collins, Margaret H.; Gonsalves, Nirmala; Falk, Gary W.; Spergel, Jonathan M.; Hirano, Ikuo; Chehade, Mirna; Schoepfer, Alain M.; Menard-Katcher, Calies; Katzka, David A.; Bonis, Peter A.; Bredenoord, Albert J.; Geng, Bob; Jensen, Elizabeth T.; Pesek, Robert D.; Feuerstadt, Paul; Gupta, Sandeep K.; Lucendo, Alfredo J.; Genta, Robert M.; Hiremath, Girish; McGowan, Emily C.; Moawad, Fouad J.; Peterson, Kathryn A.; Rothenberg, Marc E.; Straumann, Alex; Furuta, Glenn T.; Aceves, Seema S.; Pediatrics, School of MedicineBackground & aims: Disease activity and severity of eosinophilic esophagitis (EoE) dictate therapeutic options and management, but the decision-making process for determining severity varies among practitioners. To reduce variability in practice patterns and help clinicians monitor the clinical course of the disease in an office setting, we aimed to create an international consensus severity scoring index for EoE. Methods: A multidisciplinary international group of adult and pediatric EoE researchers and clinicians, as well as non-EoE allergy immunology and gastroenterology experts, formed 3 teams to review the existing literature on histology, endoscopy, and symptoms of EoE in the context of progression and severity. A steering committee convened a 1-day virtual meeting to reach consensus on each team's opinion on salient features of severity across key clinicopathologic domains and distill features that would allow providers to categorize disease severity. Results: Symptom features and complications and inflammatory and fibrostenotic features on both endoscopic and histologic examination were collated into a simplified scoring system-the Index of Severity for Eosinophilic Esophagitis (I-SEE)-that can be completed at routine clinic visits to assess disease severity using a point scale of 0-6 for mild, 7-14 for moderate, and ≥15 for severe EoE. Conclusions: A multidisciplinary team of experts iteratively created a clinically usable EoE severity scoring system denominated "I-SEE" to guide practitioners in EoE management by standardizing disease components reflecting disease severity beyond eosinophil counts. I-SEE should be validated and refined using data from future clinical trials and routine clinical practice to increase its utilization and functionality.Item Creating a multi-center rare disease consortium - the Consortium of Eosinophilic Gastrointestinal Disease Researchers (CEGIR)(IOS Press, 2017-12-18) Cheng, Katherine; Gupta, Sandeep K.; Kantor, Susanna; Kuhl, Jonathan T.; Aceves, Seema S.; Bonis, Peter A.; Capocelli, Kelley E.; Carpenter, Christina; Chehade, Mirna; Collins, Margaret H.; Dellon, Evan S.; Falk, Gary W.; Gopal-Srivastava, Rashmi; Gonsalves, Nirmala; Hirano, Ikuo; King, Eileen C.; Leung, John; Krischer, Jeffrey P.; Mukkada, Vincent A.; Schoepfer, Alain; Spergel, Jonathan M.; Straumann, Alex; Yang, Guang-Yu; Furuta, Glenn T.; Rothenberg, Marc E.; Pediatrics, School of MedicineEosinophilic gastrointestinal disorders (EGIDs) affect various segments of the gastrointestinal tract. Since these disorders are rare, collaboration is essential to enroll subjects in clinical studies and study the broader population. The Rare Diseases Clinical Research Network (RDCRN), a program of the National Center for Advancing Translational Sciences (NCATS), funded the Consortium of Eosinophilic Gastrointestinal Disease Researchers (CEGIR) in 2014 to advance the field of EGIDs. CEGIR facilitates collaboration among various centers, subspecialties, patients, professional organizations and patient-advocacy groups and includes 14 clinical sites. It has successfully initiated two large multi-center clinical studies looking to refine EGID diagnoses and management. Several pilot studies are underway that focus on various aspects of EGIDs including novel therapeutic interventions, diagnostic and monitoring methods, and the role of the microbiome in pathogenesis. CEGIR currently nurtures five physician-scholars through a career training development program and has published more than 40 manuscripts since its inception. This review focuses on CEGIR's operating model and progress and how it facilitates a framework for exchange of ideas and stimulates research and innovation. This consortium provides a model for progress on other potential clinical areas.Item 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 MedicineBackground 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.Item Food‐induced immediate response of the esophagus—A newly identified syndrome in patients with eosinophilic esophagitis(Wiley, 2021-01) Biedermann, Luc; Holbreich, Mark; Atkins, Dan; Chehade, Mirna; Dellon, Evan S.; Furuta, Glenn T.; Hirano, Ikuo; Gonsalves, Nirmala; Greuter, Thomas; Gupta, Sandeep; Katzka, David A.; De Rooij, Willemijn; Safroneeva, Ekaterina; Schoepfer, Alain; Schreiner, Philipp; Simon, Dagmar; Simon, Hans Uwe; Warners, Marijn; Bredenoord, Albert-Jan; Straumann, Alex; Pediatrics, School of MedicineBackground Dysphagia is the main symptom of adult eosinophilic esophagitis (EoE). We describe a novel syndrome, referred to as “food-induced immediate response of the esophagus” (FIRE), observed in EoE patients. Methods Food-induced immediate response of the esophagus is an unpleasant/painful sensation, unrelated to dysphagia, occurring immediately after esophageal contact with specific foods. Eosinophilic esophagitis experts were surveyed to estimate the prevalence of FIRE, characterize symptoms, and identify food triggers. We also surveyed a large group of EoE patients enrolled in the Swiss EoE Cohort Study for FIRE. Results Response rates were 82% (47/57) for the expert and 65% (239/368) for the patient survey, respectively. Almost, 90% of EoE experts had observed the FIRE symptom complex in their patients. Forty percent of EoE patients reported experiencing FIRE, more commonly in patients who developed EoE symptoms at a younger age (mean age of 46.4 years vs 54.1 years without FIRE; P < .01) and in those with high allergic comorbidity. Food-induced immediate response of the esophagus symptoms included narrowing, burning, choking, and pressure in the esophagus appearing within 5 minutes of ingesting a provoking food that lasted less than 2 hours. Symptom severity rated a median 7 points on a visual analogue scale from 1 to 10. Fresh fruits/vegetables and wine were the most frequent triggers. Endoscopic food removal was significantly more commonly reported in male patients with vs without FIRE (44.3% vs 27.6%; P = .03). Conclusions Food-induced immediate response of the esophagus is a novel syndrome frequently reported in EoE patients, characterized by an intense, unpleasant/painful sensation occurring rapidly and reproducibly in 40% of surveyed EoE patients after esophageal contact with specific foods.Item International consensus recommendations for eosinophilic gastrointestinal disease nomenclature(Elsevier, 2022-02-16) Dellon, Evan S.; Gonsalves, Nirmala; Abonia, J. Pablo; Alexander, Jeffrey A.; Arva, Nicoleta C.; Atkins, Dan; Attwood, Stephen E.; Auth, Marcus K.H.; Bailey, Dominique D.; Biederman, Luc; Blanchard, Carine; Bonis, Peter A.; Bose, Paroma; Bredenoord, Albert J.; Chang, Joy W.; Chehade, Mirna; Collins, Margaret H.; Di Lorenzo, Carlo; Dias, Jorge Amil; Dohil, Ranjan; Dupont, Christophe; Falk, Gary W.; Ferreira, Cristina T.; Fox, Adam T.; Genta, Robert M.; Greuter, Thomas; Gupta, Sandeep K.; Hirano, Ikuo; Hiremath, Girish S.; Horsley-Silva, Jennifer L.; Ishihara, Shunji; Ishimura, Norihisa; Jensen, Elizabeth T.; Gutiérrez-Junquera, Carolina; Katzka, David A.; Khoury, Paneez; Kinoshita, Yoshikazu; Kliewer, Kara L.; Koletzko, Sibylle; Leung, John; Liacouras, Chris A.; Lucendo, Alfredo J.; Martin, Lisa J.; McGowan, Emily C.; Menard-Katcher, Calies; Metz, David C.; Miller, Talya L.; Moawad, Fouad J.; Muir, Amanda B.; Mukkada, Vincent A.; Murch, Simon; Nhu, Quan M.; Nomura, Ichiro; Nurko, Samuel; Ohtsuka, Yoshikazu; Oliva, Salvatore; Orel, Rok; Papadopoulou, Alexandra; Patel, Dhyanesh A.; Pesek, Robert D.; Peterson, Kathryn A.; Philpott, Hamish; Putnam, Philip E.; Richter, Joel E.; Rosen, Rachel; Ruffner, Melanie A.; Safroneeva, Ekaterina; Schreiner, Philipp; Schoepfer, Alain; Schroeder, Shauna R.; Shah, Neil; Souza, Rhonda F.; Spechler, Stuart J.; Spergel, Jonathan M.; Straumann, Alex; Talley, Nicholas J.; Thapar, Nikhil; Vandenplas, Yvan; Venkatesh, Rajitha D.; Vieira, Mario C.; von Arnim, Ulrike; Walker, Marjorie M.; Wechsler, Joshua B.; Wershil, Barry K.; Wright, Benjamin L.; Yamada, Yoshiyuki; Yang, Guang-Yu; Zevit, Noam; Rothenberg, Marc E.; Furuta, Glenn T.; Aceves, Seema S.; Pediatrics, School of MedicineBackground & Aims Substantial heterogeneity in terminology used for eosinophilic gastrointestinal diseases (EGID), particularly the catchall term “eosinophilic gastroenteritis”, limits clinical and research advances. We aimed to achieve an international consensus for standardized EGID nomenclature. Methods This consensus process utilized Delphi methodology. An initial naming framework was proposed and refined in iterative fashion, then assessed in a first round of Delphi voting. Results were discussed in two consensus meetings, the framework was updated, and re-assessed in a second Delphi vote, with a 70% threshold set for agreement. Results Of 91 experts participating, 85 (93%) completed the first and 82 (90%) completed the second Delphi surveys. Consensus was reached on all but two statements. “EGID” was the preferred umbrella term for disorders of GI tract eosinophilic inflammation in the absence of secondary causes (100% agreement). Involved GI tract segments will be named specifically and use an “Eo” abbreviation convention: eosinophilic gastritis (now abbreviated EoG), eosinophilic enteritis (EoN), and eosinophilic colitis (EoC). The term “eosinophilic gastroenteritis” is no longer preferred as the overall name (96% agreement). When >2 GI tract areas are involved, the name should reflect all of the involved areas. Conclusions This international process resulted in consensus for updated EGID nomenclature for both clinical and research use. EGID will be the umbrella term rather than “eosinophilic gastroenteritis”, and specific naming conventions by location of GI tract involvement are recommended. As more data are developed, this framework can be updated to reflect best practices and the underlying science.Item Long-term Efficacy and Tolerability of RPC4046 in an Open-Label Extension Trial of Patients With Eosinophilic Esophagitis(Elsevier, 2021-03) Dellon, Evan S.; Collins, Margaret H.; Rothenberg, Marc E.; Assouline-Dayan, Yehudith; Evans, Larry; Gupta, Sandeep; Schoepfer, Alain; Straumann, Alex; Safroneeva, Ekaterina; Rodriguez, Cristian; Minton, Neil; Hua, Steven Y.; Hirano, Ikuo; Pediatrics, School of MedicineBackground & Aims The short-term efficacy of RPC4046, a monoclonal antibody against interleukin-13, has been shown in patients with eosinophilic esophagitis (EoE). We investigated the long-term efficacy and safety of RPC4046 in an open-label, long-term extension (LTE) study in adults with EoE. Methods We analyzed data from 66 patients who completed the 16-week, double-blind, induction portion of a phase 2 study of RPC4046 (180 mg or 360 mg/wk) vs placebo and then completed a 52-week LTE, receiving open-label RPC4046 360 mg/wk. The study was conducted at 28 centers in 3 countries; patients were enrolled between September 2014 and January 2017. Outcomes were stratified by double-blind dose group and included esophageal eosinophil counts, EoE endoscopic reference score, EoE histologic scoring system score, symptom-based EoE activity index score, and safety. Results By week 12 of the LTE, esophageal eosinophil mean and peak counts, total EoE endoscopic reference scores, and EoE histologic scoring system grade and stage scores did not differ considerably between patients who originally received placebo vs RPC4046. Most patients maintained responses through week 52. Symptom remission (symptom-based EoE activity index score, ≤20) increased from 14% at LTE entry to 67% at LTE week 52 in placebo‒RPC4046 patients and from 30% to 54% in RPC4046‒RPC4046 (either dose) patients. Of the 28 patients who did not have a histologic response to RPC4046 during the double-blind induction phase, 10 patients (36%) achieved response during the LTE. The most common adverse events were upper respiratory tract infection (21%) and nasopharyngitis (14%). Conclusions One year of treatment with RPC4046 is generally well tolerated and results in continued improvement and/or maintenance of endoscopic, histologic, and clinical measures of EoE disease activity relative to baseline.Item Monitoring patients with eosinophilic esophagitis in routine clinical practice - International Expert Recommendations(Elsevier, 2023) von Arnim, Ulrike; Biedermann, Luc; Aceves, Seema S.; Bonis, Peter A.; Collins, Margaret H.; Dellon, Evan S.; Furuta, Glenn T.; Gonsalves, Nirmala; Gupta, Sandeep; Hirano, Ikuo; Lucendo, Alfredo J.; Miehlke, Stephan; Oliva, Salvatore; Schlag, Christoph; Schoepfer, Alain; Straumann, Alex; Vieth, Michael; Bredenoord, Albert J.; Pediatrics, School of MedicineBackground & Aims There are no studies or recommendations on optimal monitoring strategies for patients with eosinophilic esophagitis (EoE). Our objective was to develop guidance on how to monitor EoE patients in routine clinical practice, on the basis of available clinical evidence and expert opinion. Methods A multidisciplinary, international group of EoE experts identified the following important three questions during several consensus meetings: why, by what means and when to monitor EoE patients. A steering committee was named and three teams were formed to review literature and to formulate statements for each topic. In a Delphi survey a level of agreement of ≥75% was defined as threshold value for acceptance. In a final conference, results were presented, critical points and comments on the statements were discussed and statements were rephrased/rewritten if necessary. Results 18 EoE experts (14 adult and pediatric gastroenterologists, 2 pathologists and 2 allergists) with a median of 21.7 years in clinical practice, mostly academic or university- based, completed the Delphi survey, which included 11 statements and a proposed algorithm for monitoring EoE patients. Each statement attained ≥75% agreement. Participants discussed and debated mostly about the statement concerning surveillance intervals for EoE patients with stable disease. Conclusions It was concluded that effective maintenance treatment probably reduces the development of EoE complications, and regular, structured and under certain conditions individualized clinical follow-up is recommended to assess disease activity while opening a window to monitoring side-effects, adjusting therapy and encouraging adherence to treatment. Follow-up should comprise symptom assessment and periodic or repeated endoscopy with histological assessment in specific EoE settings.Item Proton Pump Inhibitor-Responsive Oesophageal Eosinophilia: An Entity Challenging Current Diagnostic Criteria for Eosinophilic Oesophagitis(BMJ, 2016-03) Molina-Infante, Javier; Bredenoord, Albert J.; Cheng, Edaire; Dellon, Evan S.; Furuta, Glenn T.; Gupta, Sandeep K.; Hirano, Ikuo; Katzka, David A.; Moawad, Fouad J.; Rothenberg, Marc E.; Schoepfer, Alain; Spechler, Stuart; Wen, Ting; Straumann, Alex; Lucendo, Alfredo J.; Department of Pediatrics, IU School of MedicineConsensus diagnostic recommendations to distinguish GORD from eosinophilic oesophagitis (EoE) by response to a trial of proton pump inhibitors (PPIs) unexpectedly uncovered an entity called 'PPI-responsive oesophageal eosinophilia' (PPI-REE). PPI-REE refers to patients with clinical and histological features of EoE that remit with PPI treatment. Recent and evolving evidence, mostly from adults, shows that patients with PPI-REE and patients with EoE at baseline are clinically, endoscopically and histologically indistinguishable and have a significant overlap in terms of features of Th2 immune-mediated inflammation and gene expression. Furthermore, PPI therapy restores oesophageal mucosal integrity, reduces Th2 inflammation and reverses the abnormal gene expression signature in patients with PPI-REE, similar to the effects of topical steroids in patients with EoE. Additionally, recent series have reported that patients with EoE responsive to diet/topical steroids may also achieve remission on PPI therapy. This mounting evidence supports the concept that PPI-REE represents a continuum of the same immunological mechanisms that underlie EoE. Accordingly, it seems counterintuitive to differentiate PPI-REE from EoE based on a differential response to PPI therapy when their phenotypic, molecular, mechanistic and therapeutic features cannot be reliably distinguished. For patients with symptoms and histological features of EoE, it is reasonable to consider PPI therapy not as a diagnostic test, but as a therapeutic agent. Due to its safety profile, ease of administration and high response rates (up to 50%), PPI can be considered a first-line treatment before diet and topical steroids. The reasons why some patients with EoE respond to PPI, while others do not, remain to be elucidated.Item 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 MedicineBackground 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.Item Symptoms Have Modest Accuracy in Detecting Endoscopic and Histologic Remission in Adults With Eosinophilic Esophagitis(Elsevier, 2016-03) Safroneeva, Ekaterina; Straumann, Alex; Coslovsky, Michael; Zwahlen, Marcel; Kuehni, Claudia E.; Panczak, Radoslaw; Haas, Nadine A.; Alexande, Jeffrey A.; Dellon, Evan S.; Gonsalves, Nirmala; Hirano, Ikuo; Leung, John; Bussmann, Christian; Collins, Margaret H.; Newbury, Robert O.; De Petris, Giovanni; Smyrk, Thomas C.; Woosley, John T.; Yan, Pu; Yang, Guang-Yu; Romero, Yvonne; Katzka, David A.; Furuta, Glenn T.; Gupta, Sandeep K.; Aceves, Seema S.; Chehade, Mirna; Spergel, Jonathan M.; Schoepfer, Alain M.; International Eosinophilic Esophagitis Activity Index Study Group; Pediatrics, School of MedicineBACKGROUND & AIMS: It is not clear whether symptoms alone can be used to estimate the biologic activity of eosinophilic esophagitis (EoE). We aimed to evaluate whether symptoms can be used to identify patients with endoscopic and histologic features of remission. METHODS: Between April 2011 and June 2014, we performed a prospective, observational study and recruited 269 consecutive adults with EoE (67% male; median age, 39 years old) in Switzerland and the United States. Patients first completed the validated symptom-based EoE activity index patient-reported outcome instrument and then underwent esophagogastroduodenoscopy with esophageal biopsy collection. Endoscopic and histologic findings were evaluated with a validated grading system and standardized instrument, respectively. Clinical remission was defined as symptom score <20 (range, 0-100); histologic remission was defined as a peak count of <20 eosinophils/mm(2) in a high-power field (corresponds to approximately <5 eosinophils/median high-power field); and endoscopic remission as absence of white exudates, moderate or severe rings, strictures, or combination of furrows and edema. We used receiver operating characteristic analysis to determine the best symptom score cutoff values for detection of remission. RESULTS: Of the study subjects, 111 were in clinical remission (41.3%), 79 were in endoscopic remission (29.7%), and 75 were in histologic remission (27.9%). When the symptom score was used as a continuous variable, patients in endoscopic, histologic, and combined (endoscopic and histologic remission) remission were detected with area under the curve values of 0.67, 0.60, and 0.67, respectively. A symptom score of 20 identified patients in endoscopic remission with 65.1% accuracy and histologic remission with 62.1% accuracy; a symptom score of 15 identified patients with both types of remission with 67.7% accuracy. CONCLUSIONS: In patients with EoE, endoscopic or histologic remission can be identified with only modest accuracy based on symptoms alone. At any given time, physicians cannot rely on lack of symptoms to make assumptions about lack of biologic disease activity in adults with EoE.