The FDA has granted approval for two medications in the treatment of Eosinophilic Esophagitis (EoE)鈥攖he first oral medication tailored for adults and the exclusive therapeutic option for children. Evan Dellon, MD, MPH, internationally known for his work with EoE, and colleagues continue to focus on optimizing usage for effective, personalized outcomes.
Eosinophilic Esophagitis (EoE) is an allergic inflammatory disorder that affects the esophagus, causing distressing symptoms such as difficulty swallowing in adolescents and adults, and vomiting and abdominal pain in children. Evan Dellon, MD, MPH, a gastroenterologist at the University of North Carolina, has been at the forefront of groundbreaking developments in EoE treatment.
, published in the journal Clinical Gastroenterology and Hepatology helped lead to the recent FDA approval of budesonide, the sole oral therapy designed for individuals aged 11 and older with EoE鈥攁 significant milestone Dr. Dellon and colleagues have been diligently working towards for more than 10 years. Prior to this approval patients had to make 鈥渉ome brews鈥� of budesonide slurries by adapting asthma medications that were originally formulated for nebulizer machines.
the twice-daily treatment will be available in single-dose stick packs (2mg/10mL) by the end of February. Dr. Dellon, part of the research team, demonstrated budesonide’s efficacy in achieving histologic remission and improving swallowing ability in patients.
Key findings from the two multicenter, randomized, double-blind, parallel-group, placebo-controlled 12-week studies include:
- 53.1% () and 38% () of patients receiving budesonide achieved histologic remission compared to 1% (Study 1) and 2.4% (Study 2) in the placebo group.
- Patients taking budesonide reported less difficulty swallowing.
- Budesonide has not been shown to be safe and effective for the treatment of EoE for longer than 12 weeks.
Pediatric Patients with EoE
Additionally, the aged one to eleven, marking a significant advancement in addressing this condition.
Previously, there was a void in approved medications for pediatric EoE patients. Dr. Dellon was one of the lead investigators, along with Sabina Mir, MD, 黑料网 pediatric gastroenterologist, who headed 黑料网 as a clinical trial site for the study that influenced this approval.
鈥淭his is the first medication to be approved for this younger population of children with EoE, addressing a critical need for therapy in this group and providing a treatment that can improve multiple EoE disease features and hopefully prevent complications like future esophageal stricturing,” Dr. Dellon said.
Dupilumab for Adolescents and Adults
It鈥檚 been almost two years since dupilumab was first approved to treat individuals 12 and older with EoE, another milestone that to which . He says the real-world use of dupilumab mirrors the promising outcomes observed during the clinical trials.
鈥淚t’s been very impactful, I have probably more than 100 people on it now,鈥� Dellon said. 鈥淚 had a large cohort of patients who just didn’t respond to other treatments and were waiting for something like this to become available.鈥�
Historically, physicians relied on food elimination diets, off-label treatments, such as stomach acid reducers (proton pump inhibitors) or asthma steroid medications (which are swallowed to coat the esophagus rather than inhaled) and stretching the esophagus with dilation during endoscopy.
鈥淢any of them had esophageal strictures so the esophagus was mechanically stretched to help them decrease their symptoms of trouble swallowing,鈥� Dellon said. 鈥淎fter three or six months, they would come back and the esophagus would just shrink back again, because all the inflammation was still going on.鈥�
published in the journal Clinical Gastroenterology and Hepatology by Christopher Lee, MD, 黑料网 internal medicine resident, and Dr. Dellon analyzed 46 patients with severe EoE who had undergone multiple esophageal dilations. They found that many patients experienced remission and sustained improvements in esophageal diameter upon dupilumab treatment. Although, these findings are promising more research is needed to determine longer-term treatment outcomes for severe EoE and whether dupilumab could be used earlier, for example right after diagnosis, for these most affected patients.
The Road Ahead
As the spotlight remains on EoE treatment, the focus now shifts to understanding dupilumab鈥檚 optimal utilization, considering factors such as disease progression, response variations, and dosing frequence long-term. Clinical trial participants had EoE an average duration of five years since diagnosis, coupled with unresponsiveness to proton pump inhibitors, when they entered the study. However, uncertainty lingers regarding whether newly diagnosed patients will exhibit similar responses or fare better than those in the trials. Additionally, the efficacy of dupilumab in more severe cases of EoE needs to be studied in more depth, and several studies related to this are opening soon at 黑料网 and other sites. Dupilumab鈥檚 recommended dosage for EoE treatment is a weekly regimen, a departure from its alternative bi-weekly uses in treating asthma and eczema.
鈥淭hat was primarily because we only saw symptom benefit with weekly dosing in the approval study,鈥� Dellon said. 鈥淗owever, the question is, as people feel well, can you decrease the intensity of the therapy long term? It’s a very expensive medicine, so understanding how to best use those resources is pretty critical.鈥�
Interestingly, a series of trials explored the impact of medications that removed eosinophils (white blood cells that inflame the esophagus) from the body on EoE. The assumption was patients would get better.
鈥淲hat we saw in these studies were that the eosinophils went away on the biopsies, so the medication was working biologically, but there were still other persistent changes when you look under the microscope that didn’t get better,鈥� Dellon said. 鈥淎nd when you look at the esophagus, it wasn’t improved visually either and patient’s symptoms didn’t improve. This raises this question of, well, what else is driving the disease if it鈥檚 not the eosinophil?鈥�
The ultimate goal is to tailor treatment strategies based on the specific pathogenic mechanisms driving each patient’s condition. Dr. Dellon’s aims for a future where a comprehensive understanding of EoE profiles guides the selection of biologics, dietary interventions, and steroid therapies with precision. This personalized approach holds the promise of more effective and sustainable outcomes for individuals grappling with the challenges of Eosinophilic Esophagitis.