Dupilumab (Dupixent) for Eosinophilic Esophagitis
Myron Yaster MD
At the beginning of my medical school surgical rotation, the most common surgical procedure on the OR schedule was partial vagotomy for gastric ulcer disease. At the end of my 12 week rotation the surgical procedure completely disappeared because of the introduction of the H2 blocker cimetidine. Could a similar revolution be upon us for eosinophilic esophagitis? YES! In today’s PAAD we’ll review the results of an exciting new study by Chehade et al.1 in which dupilumab (Dupixent) significantly reduced esophageal eosinophil counts and improved histologic, endoscopic, and transcriptomic measures as compared with placebo, What has this got to do with pediatric anesthesia? A lot! Many of the upper GI endoscopies that are done under general anesthesia may no longer be necessary, just like the surgical vagotomies for gastric ulcer disease in the past. Myron Yaster MD
Original article
Chehade M, Dellon ES, Spergel JM, Collins MH, Rothenberg ME, Pesek RD, Hirano I, Liu R, Laws E, Mortensen E, Martincova R, Shabbir A, McCann E, Kamal MA, Kosloski MP, Hamilton JD, Samuely C, Lim WK, Wipperman MF, Farrell A, Patel N, Yancopoulos GD, Glotfelty L, Maloney J. Dupilumab for Eosinophilic Esophagitis in Patients 1 to 11 Years of Age. N Engl J Med. 2024 Jun 27;390(24):2239-2251. doi: 10.1056/NEJMoa2312282. PMID: 38924731.
Children with eosinophilic esophagitis (EoE) suffer from multiple symptoms including abdominal pain, vomiting, regurgitation, trouble swallowing and food impaction. In addition, when EoE affects children at a young age, it can severely impact their ability to eat and can cause failure to thrive at a critical time of their growth and development. “Dupilumab (Dupixent, Sanofi, Regeneron) is a human monoclonal antibody that blocks interleukin-4 and interleukin-13 pathways and has shown efficacy in five different atopic diseases marked by type 2 inflammation, including eosinophilic esophagitis in adults and adolescents.”1 In this randomized controlled trial, “patients 1 to 11 years of age with active eosinophilic esophagitis who had had no response to proton-pump inhibitors were randomly assigned to 16 weeks of a higher-exposure or lower-exposure subcutaneous dupilumab regimen or to placebo. The primary end point was histologic remission (peak esophageal intraepithelial eosinophil count, ≤6 per high-power field) at week 16. Key secondary end points were tested hierarchically.”1
“Dupilumab resulted in histologic remission in a significantly higher percentage of children with eosinophilic esophagitis than placebo. The higher-exposure dupilumab regimen also led to improvements in measures of key secondary end points as compared with placebo.”1 The results of this trial led the FDA to approve dupilumab to treat EoE in children 1-11 years of age. These findings in children aged 1 to 11 years are similar to the studies of patients aged 12 years and older2, so there are no real surprises in this study except that based on these results and with FDA approval therapy can start at a very young age. Also note that dupilumab has been a very effective biologic in a number of other allergic diseases like atopic dermatitis. These outcomes in EoE as well as in other approved applications have been and will be life-changing for many patients.
With all of the depressing news in the world, isn’t it great to know about a new medical miracle? Send your thoughts and comments to Myron who will post in a Friday reader response.
References
1. Chehade M, Dellon ES, Spergel JM, et al. Dupilumab for Eosinophilic Esophagitis in Patients 1 to 11 Years of Age. The New England journal of medicine 2024;390(24):2239-2251. (In eng). DOI: 10.1056/NEJMoa2312282.
2. Rothenberg ME, Dellon ES, Collins MH, et al. Efficacy and safety of dupilumab up to 52 weeks in adults and adolescents with eosinophilic oesophagitis (LIBERTY EoE TREET study): a multicentre, double-blind, randomised, placebo-controlled, phase 3 trial. Lancet Gastroenterol Hepatol 2023;8(11):990-1004. (In eng). DOI: 10.1016/s2468-1253(23)00204-2.