Rapid resolution of eosinophilic esophagitis with dupilumab treatmentArsal Khan1,*, Isabel O’Connell1,*, Wayne G. Shreffler1, Joel A. Frielander2,Qian Yuan1,#1. Food Allergy Center, Massachusetts General Hospital, Harvard Medical School, 55 Fruit St, Boston, MA 021142. EvoEndo Inc. 12649 E. Caley Avenue, Suite 116, Centennial, CO 80111*These authors contributed equally#Corresponding authorCorresponding author:Qian Yuan, MD, PhDFood Allergy Center, Massachusetts General Hospital, Harvard Medical SchoolBoston, MA, 02114, USAPhone: 617-726-8706FAX: 617-724-7011Email: qyuan@mgh.harvard.eduTo the Editor,Eosinophilic esophagitis (EoE) is a chronic inflammatory condition of the esophagus, triggered in most patients by dietary allergens (1). It affects both children and adults with a bimodal appearance in onset of symptoms between 5-10 years of age in children and 20-30 years in adults. It has, however, also been diagnosed in children younger than 5 years old. The disease burden of EoE has had a negative impact on many patients’ quality of life (QoL) (2).EoE requires a clinical pathological diagnosis and the presence of both clinical symptoms and abnormal tissue eosinophilia as noted by ≥15 eosinophils per high power field (hpf) in the esophageal mucosa (1). For diagnosis and monitoring of disease activity, repeated esophagogastroduodenoscopy (EGD) with biopsies under sedation is the standard of care but can be limiting (1).Dupilumab is a recently FDA-approved treatment for patients with EoE who are greater than 1 year of age and over 10 kg. It is a monoclonal antibody targeting the IL-4Rα chain, suppressing IL-4 and IL-13 signaling (3). Clinical trials in adults (4) and in children with EoE (5) have demonstrated its great efficacy in controlling both EoE symptoms and esophageal tissue inflammation. The efficacy of dupilumab on esophageal eosinophilia is assessed from the mucosal biopsies obtained during sedated EGD. Althougth the injection treatment is well tolerated (4,5), pain/discomfort at the injection site is the most common complaints by patients, more so with pediatric patients because of the age and mental maturity and it has a negative impact on continuation of the treatment. Based on current clinical guidelines from the clinical trials (4,5), every patient has to receive the injection treatment either weekly or biweekly for 12 weeks until the first post-treatment EGD to assess the efficacy of the treatment.With the intention to study the time course of mucosal response to dupilumab treatment in EoE, we are conducting a clinical study at the Massachusetts General Hospital, approved by the hospital’s Institutional Review Board (#2023P002300). In this study, we use a sedation-free transnasal endoscopic (TNE) approach and utilize the EvoEndo Model LE ultra-slim gastroscope (EvoEndo, Inc, Centennial, Colorado) to perform transnasal esophagoscopies with biopsies (TN-Eso). Written informed consent was obtained from all participating patients and their parent as reqired by the study protocol.TN-Eso with Virtual Reality (VR) distraction and dissociation is a novel endoscopic technique that does not require general anesthesia or any sedation (6,7). It has been shown to be safe and well-tolerated in children and adults, and it allows pediatric and adult gastroenterologists to more frequently monitor the EoE disease activity without sedation or anesthesia. TN-Eso also offers the opportunity to systemically study the kinetics of tissue eosinophilia in EoE when initiating dupilumab treatment or other treatments. For the very first time, it allows us to obtain adequate tissue biopsy specimens under direct visualization at much shorter intervals. It does this without sacrificing patient safety or cost concerns associated with the use of repetitive sedation (6,7).Here, we present the novel and important results of the first 3 cases in this study treated with duplimab. In all cases, dupilumab treatment was 300 mg weekly subcutaneous injections. Following baseline standard EGD with biopsy, each patient underwent 2 TN-Eso after initiating dupilumab treatment at 3-4 weeks and 6-8 weeks (Fig. 1). All 3 patients reported clinical symptom improvement after 2 weeks of treatment, and complete resolution of symptoms after 3-4 weeks of treatment. Tissue eosinophilia of EoE was assessed by board-certified pathologists using standard H&E staining of the esophageal biopsies and reported as eosinophils/high power field (eos/HPF) (Table 1). Marked improvement of tissue eosinophilia (< 5 eos/HPF) was observed in all 3 patients with the first TNE at 3-4 weeks, and persistent with the second endoscopy at 7-8 weeks post initiating dupilumab treatment (Table 1).We here report the first series of cases demonstrating rapid resolution of clinical symptoms and tissue eosinophilia of EoE within 3-4 weeks after starting therapy dupilumab. Based on the published clinical trials of dupilumab in EoE (4,5), clinicians perform a conventional sedated EGD with general anesthesia three months (12 weeks) after initiating the treatment, to assess efficacy and response. With the availability of sedation-free TNE, we were able to evaluate the efficacy of dupilumab on EoE in much shorter time intervals. This data indicates the rapid effect of dupilumab on clinical symptoms and esophageal eosinophilia in EoE patients and the possibility of evaluating clinical response sooner than the usually performed, this will avoid unnecessary treatment in non-responsive patients to reduce cost associated with the therapy and more importantly and more revalently in pediatric patients to reduce the discomfort associated with the injections with fewer treatments before the efficacy is assessed. Therefore, this not only helps to guide clinical decision making on treatment, but may also decrease the cost of care and facilitate faster improvement of patients’ QoL. Large scale prospective study is needed to further validate our findings.References:Muir A, and Falk GW. Eosinophilic esophagitis: a review. JAMA 2021;326(13):1310-1318.Mukkada V, Falk GW, Eichinger CS, King D, Todorova L, Shaheen NJ. Health-related quality of life and costs associated with eosinophilic esophagitis: a systematic review. Clin Gastroenterol Hepatol 2018;16(4):495-503.e8.Harb H, and Chatila T. Mechanisms of dupilumab. Cli Exp Allergy 2020;50(1):5-14.Dellon ES, Rothenberg ME, Collins MH, et al. N Eng J Med 2022;387(25):2317-2330.Chehade M, Dellon ES, Spergel JM, et al. N Eng J Med 2024;390(24):2239-2251.Friedlander JA, DeBoer EM, Soden JS, et al. Unsedated transnasal esophagoscopy for monitoring therapy in pediatric eosinophilic esophagitis. Gastrointest Endosc. 2016;83(2):299-306 e1.Nguyen, Nathalie, William J. Lavery, Kelley E. Capocelli, Clinton Smith, Emily M. DeBoer, Robin Deterding, Jeremy D. Prager, et al. 2019. “Transnasal Endoscopy in Unsedated Children With Eosinophilic Esophagitis Using Virtual Reality Video Goggles.” Clinical Gastroenterology and Hepatology: The Official Clinical Practice Journal of the American Gastroenterological Association 17 (12): 2455–62.
