Eosinophilic esophagitis: promising therapy, biomarkers, and assessment tools
Emerging Diagnostic and Monitoring Approaches in Eosinophilic Gastrointestinal Diseases (EGID)
Symposium presented Saturday, February 25, 2023
Moderator
Melanie A. Ruffner, MD PhD
Assistant Professor of Pediatrics, University of Pennsylvania Perelman School of Medicine
Presenters
Evan S. Dellon, MD, MPH
Professor of Medicine and Adjunct Professor of Epidemiology, University of North Carolina School of Medicine, Chapel Hill
Director, Center for Esophageal Diseases and Swallowing
Treatment of Eosinophilic Esophagitis (EoE): Breakthrough in Biologics
Justin Schwartz, MD, PhD
Assistant Professor, University of Cincinnati College of Medicine
Blood and Urine Biomarkers of Eosinophilic Gastrointestinal Disorders
Seema S. Aceves, MD, PhD
Professor of Pediatrics and Medicine, Division of Allergy, Immunology, University of California, San Diego
Severity of Eosinophilic Esophagitis (EoE)
New diagnostic, monitoring, and treatment approaches are available for eosinophilic gastrointestinal diseases, including breakthroughs in eosinophilic esophagitis with new biologics and biomarkers.
The recent approval of dupilumab for treatment of eosinophilic esophagitis (EOE), research into better biomarkers, and the anticipated availability of a metric to assess EOE severity all bode well for patients. Speakers considered the ramifications of these developments.
Breakthroughs in biologic therapy for eosinophilic esophagitis
Biologics and other novel therapies are needed for treatment of EoE because of suboptimal response rates to proton pump inhibitors (PPIs), most topical steroids, and dietary approaches, said Evan S. Dellon MD, MPH, professor of medicine at University of North Carolina Chapel Hill School of Medicine. Adherence to dietary therapy is difficult for many patients, especially long-term. EoE is a chronic condition, so maintenance therapy is needed. Currently, there are no orally available nonsteroidal medications.
Dupilumab, an interleukin-4 receptor alpha antagonist monoclonal antibody with several indications approved by the US Food and Drug Administration (FDA), is the first biologic to be FDA-approved for EoE in patients age 12 and older who weigh at least 40 kg. Other monoclonal antibodies are under development for treatment of EoE:
- Cendakimab: phase 2 trial has been completed
- Lirentelimab: phase 3 trial has been completed
- Benralizumab: phase 3 trial has been completed
- There are 8 additional emerging treatments, and more to come
The exact place for biologics in treatment algorithms is not yet defined. Still needed is information on long-term safety, efficacy, immunogenicity, and cost on these new pharmacotherapies.
Where does dupilumab fit into the clinical treatment plan? Dr. Dellon advises considering it for patients who do not respond to other treatments, keeping in mind that because of cost, insurance coverage will likely require prior authorization and documentation of prior therapy with no response. For earlier treatment, a PPI is preferable before turning to a biologic, always considering the patient and their preferences and characteristics.
Dr. Dellon urged healthcare professionals to inform patients about EGID Partners, an online registry of patients with eosinophilic gastrointestinal diseases (EGIDs) that offers resources for patients as well as researchers.
Blood and urine biomarkers hold promise
There is a need for noninvasive biomarkers for EoE. Endoscopy, the only current option for diagnosis and surveillance, carries a significant burden because it is invasive, expensive, requires significant time off from work or school, causes patient stress, and carries a risk of adverse events, especially related to the anesthesia.
Justin Schwartz, MD, PhD, said that an ideal biomarker would be noninvasive, accurate, and validated in a large varied cohort, and would reflect the underlying disease pathogenesis. Several difficulties in identifying an EoE marker include having it configured to reflect the specific organ, and offering the ability to identify active versus inactive disease.
Over the past 10 years, attempts to identify biomarkers have included blood plasma, urine, stool, oropharyngeal swabs, and exhaled breath. Dr. Schwartz, assistant professor at the University of Cincinnati College of Medicine, reported that blood and urine biomarkers hold the most promise, but that larger prospective studies are needed.
New tool for assessing severity of eosinophilic esophagitis
The risk of stricture in chronic, severe EoE is a concern, said Seema S. Aceves, MD, PhD. Severe EoE can be characterized in several different ways, including endoscopic rings or strictures, nonresponse to therapy, persistent symptoms, and fibrosis.
To accurately assess the severity of EoE, an international team of more than 30 experts in allergy, gastroenterology, and pathology developed the Index of Severity for EoE (I-SEE). The I-SEE has 3 domains: symptoms and complications, inflammatory features, and fibrostenotic features. I-SEE can be used at initial diagnosis and then at each subsequent visit for both adults and children with EoE. According to Dr. Aceves, there are plans to make I-SEE available as an app.
Dr. Aceves advised that although many practitioners may not have access to each of these parameters, the I-SEE metric can guide conversations between clinicians and pathologists regarding features most relevant for assessing EoE severity based on the current state of the literature. Dr. Aceves is professor of pediatrics and medicine at the University of California, San Diego
Selected references
Aceves SS, Dellon ES, Greenhawt M, et al. Clinical guidance for the use of dupilumab in eosinophilic esophagitis: a yardstick. Ann Allergy Asthma Immunol 2022(Dec 13):S1081-1206(22)01997-4. doi: 10.1016/j.anai.2022.12.014. Epub ahead of print.
Dellon ES, Khoury P, Muir AB, et al. A clinical severity index for eosinophilic esophagitis: development, consensus, and future directions. Gastroenterology 2022;163(1):59-76. doi: 10.1053/j.gastro.2022.03.025
Hines BT, Rank MA, Wright BL, et al. Minimally invasive biomarker studies in eosinophilic esophagitis: a systematic review. Ann Allergy Asthma Immunol 2018(Aug);121(2):218-228. doi: 10.1016/j.anai.2018.05.005. Epub 2018 May 16.
Hirano I, Collins MH, Assouline-Dayan Y, et al. Rpc4046, a monoclonal antibody against il13, reduces histologic and endoscopic activity in patients with eosinophilic esophagitis. Gastroenterology 2019;156(3):592-603.e10. doi: 10.1053/j.gastro.2018.10.051
Sauer BG, Barnes B, McGowan EC. Strategies for the use of dupilumab in eosinophilic esophagitis. Am J Gastroenterol 2023(Jan 30). doi: 10.14309/ajg.0000000000002206. Epub ahead of print.
Spergel J, Sher L, Durrani S, et al. Dupilumab improves type 2 comorbidity outcomes in patients with eosinophilic esophagitis and comorbid disease at baseline: from Parts A and B of LIBERTY-EoE-TREET. JACI 2023;151(2):AB199. doi: 10.1016/j.jaci.2022.12.622
Disclosures
Evan S. Dellon, MD, MPH:
Consultant: Abbott, Abbvie, Adare/ Ellodi, Aimmune, Akesobio, Allakos, Amgen, Arena, AstraZeneca, Avir, Biorasi
Consulting related to EoE and EGIDs: Calypso, Celgene/Receptos/BMS, Celldex, Eli Lilly,
EsoCap, GSK, Gossamer Bio, Invea, Landos, LucidDx, Morphic, Nutricia, Parexel/Calyx, Phathom, Regeneron, Revolo, Robarts/Alimentiv, Salix, Sanofi Consulting related to EoE and EGIDs; Shire/Takeda, Target RWE
Research Grant: Adare/Ellodi, Allakos, Arena, AstraZeneca, GSK, Meritage, Miraca, Nutricia - clinical trials for EoE and EGIDs - grant is to University; Celgene/Receptos/BMS, Regeneron, Revolo, Shire/Takeda - clinical trials for EoE and EGIDs - grant is to University
Organizational: American College of Gastroenterology - Research committee; Clinical Gastroenterology and Hepatology - Associate Editor
Justin Schwartz, MD, PhD:
Consultant: Takeda - Swallowed budesonide
Research Grants: Thrasher Research Fund - Eosinophil progenitor levels as a biomarker for EoE; Knopp Biosciences - Biomarker study evaluating Dexpramipexole in subjects with eosoniphilic asthma; CEGIR - CEGIR Fellowship Grant
The other 2 faculty have no relevant disclosures.