Tag Archives: Eosinophilic esophagitis

“Real-World” Dupilumab for Eosinophilic Esophagitis

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CJ Lee, DS Dellon. Clin Gastroenterol Hepatol 2024; 22: 252-258. Open Access! Real-World Efficacy of Dupilumab in Severe, Treatment-Refractory, and Fibrostenotic Patients With Eosinophilic Esophagitis

Rationale for the retrospective study: ” Although it is the first Food and Drug Administration–approved treatment for EoE, eligibility criteria for the clinical trial program excluded several characteristics of the most severe EoE patients seen in clinical practice…Therefore, the purpose of this study was to determine the real-world efficacy of dupilumab in patients with severe, treatment-refractory, and fibrostenotic EoE.”

This cohort of 46 patients with severe disease including 39 (85%) who had prior esophageal dilatation (mean of 9). Patients had a mean age of 39 and had had symptoms for a mean of 13 years. Patients were considered treatment-refractory as all had received PPIs and topical steroids; in addition, most (87%) had tried elimination diets.

Key findings:

  • The peak eosinophil counts decreased markedly, and postdupilumab histologic response rates were 80% and 57% for fewer than 15 eosinophils per high-power field and 6 or fewer eosinophils per high-power field, respectively. Mean eosinophil count dropped from 70 to 9 following dupilumab treatment.
  • The Endoscopic Reference Score (EREFS) decreased from 4.62 to 1.89 with improvement in all categories: exudates, rings, edema, furrows and strictures.
  • Global symptom improvement was reported in 91% (P < .001).

My take: Many clinical studies are not representative of typical patients with various ailments, often excluding those with the most severe manifestations. This study indicates that dupilumab is an effective agent for patients with severe fibrostenotic eosinophilic esophagitis.

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Where I Want to Be Right Now (Honeymoon Beach, St Johns)

Practical Tips for Eosinophilic Esophagitis

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We recently had Glenn Furuta, MD give our group a terrific lecture on eosinophilic esophagitis (EoE).

Some of the key points:

  • The burden of EoE continues to increase.
  • There are clearly several phenotypes of EoE. Some patients may never develop stricturing/fibrostenotic disease  but natural history data continues to evolve.
  • After treatment response, many patients can continue with symptoms. In adults and adolescents, this has been termed ‘esophageal hypervigilance.’ Feeding therapy may be helpful in this circumstance.
  • Adrenal insufficiency: Currently their group tries to screen for this after 4 months of topical corticosteroids and then yearly. It is unusual for them identify adrenal insufficiency if the patient is receiving only a single steroid agent; patients receiving steroids for other conditions like asthma are at higher risk.
  • An esophagram with a barium coated pill can be a useful adjunct to determine if there is esophageal narrowing (this can be missed on endoscopy).
  • For select patients, endoFLIP can characterize distensibility/esophageal function
  • Esophageal strictures: Their group uses Bougie dilators and has had a good experience. No perforations. ~15% with chest pain afterwards.
  • Corticosteroids (topical) can reduce the risk of food impactions in adults.
  • Reviewed use of Dupilimab and its recent approval in EoE for children as young as 1 yr of age (>15 kg)

Some selected slides:

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Dupixent Approved in Younger Children (15 kg+)

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Link: DUPIXENT® (DUPILUMAB) FDA APPROVED AS FIRST AND ONLY TREATMENT INDICATED FOR CHILDREN AGED 1 YEAR AND OLDER WITH EOSINOPHILIC ESOPHAGITIS (EOE)

“Regeneron Pharmaceuticals, Inc. (NASDAQ: REGN) and Sanofi today announced that the U.S. Food and Drug Administration (FDA) has approved Dupixent® (dupilumab) for the treatment of pediatric patients aged 1 to 11 years, weighing at least 15 kg, with eosinophilic esophagitis (EoE).”

Recommended dosing:

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Disclaimer: This blog, gutsandgrowth, assumes no responsibility for any use or operation of any method, product, instruction, concept or idea contained in the material herein or for any injury or damage to persons or property (whether products liability, negligence or otherwise) resulting from such use or operation. These blog posts are for educational purposes only. Specific dosing of medications (along with potential adverse effects) should be confirmed by prescribing physician.  Because of rapid advances in the medical sciences, the gutsandgrowth blog cautions that independent verification should be made of diagnosis and drug dosages. The reader is solely responsible for the conduct of any suggested test or procedure.  This content is not a substitute for medical advice, diagnosis or treatment provided by a qualified healthcare provider. Always seek the advice of your physician or other qualified health provider with any questions you may have regarding a condition.

Eosinophilic Esophagitis -Increasing Incidence and Emergence of Biologic Treatments

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1st article: JW Hahn et al. Clin Gastroenterol Hepatol 2023; 21: 3270-3284. Open Access! Global Incidence and Prevalence of Eosinophilic Esophagitis, 1976–2022: A Systematic Review and Meta-analysis

This research utilized 40 studies which met the eligibility criteria, including over 288 million participants and 147,668 patients with EoE from 15 countries across the five continents.

Key findings:

  • The global pooled incidence and prevalence of EoE were 5.31 cases per 100,000 inhabitant-years and 40.04 cases per 100,000 inhabitant-years, respectively.
  • The pooled prevalence and incidence of EoE were higher in high-income countries, males, and North America.
  • The pooled prevalence and incidence of EoE have increased from 1976 to 2022.
Time trends of incidence (A) and prevalence (B) of EoE, 1976 to 2022. Pooled estimates, cases per 100,000 inhabitant-years.

2nd Article: DL Snyder, ES Dellon. Clin Gastroenterol Hepatol 2023; 21: 3230-3233. Biologics in the Treatment of Eosinophilic Esophagitis: Ready for Use?

“This review summarizes the data leading to FDA approval for dupilumab and provides a practical approach for clinical use of dupilumab.” Dupilumab, a humanized monoclonal antibody that blocks interleukin (IL)-4 receptor alpha, is currently the only FDA-approved medication for EoE. It is noted that in the trials leading to FDA approval, all patients were PPI refractory and ~70% had received topical steroids (with about half either intolerant or nonresponsive).

Dosing: 300 mg weekly injection with a single-dose prefilled autoinjector pen or a syringe with a needle shield. It is recommended that refrigerated medicine is brought to room temperature for at least 45 minutes prior to injection. It “can remain unrefrigerated up to 14 days.”

In Figure 1, the articles details positioning of use of dupilumab in EoE management algorithm:

  • New diagnosis, patient preference
  • Additional atopic condition with approved dupilumab use (strong indication)
  • Lack of response to current treatment (diet, PPI, swallowed steroids) or adverse effects from current treatment (strong indications)
  • “It is reasonable to repeat endoscopy with biopsy 24 weeks after initiation of dupilumab in many patients…However, endoscopy may be completer earlier” in selected patients.

At least 5 other biologics are in phase 2 or phase 3 studies (listed in Table 1).

My take: EoE is increasing in prevalence and new therapies (often expensive) are emerging.

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Also, there is a fairly good patient education 7-page pamphlet from the makers of Dupixent encouraging patients with symptoms suggestive of EoE to speak with their physicians.

Link: This is EoE

Disclaimer: This blog, gutsandgrowth, assumes no responsibility for any use or operation of any method, product, instruction, concept or idea contained in the material herein or for any injury or damage to persons or property (whether products liability, negligence or otherwise) resulting from such use or operation. These blog posts are for educational purposes only. Specific dosing of medications (along with potential adverse effects) should be confirmed by prescribing physician.  Because of rapid advances in the medical sciences, the gutsandgrowth blog cautions that independent verification should be made of diagnosis and drug dosages. The reader is solely responsible for the conduct of any suggested test or procedure.  This content is not a substitute for medical advice, diagnosis or treatment provided by a qualified healthcare provider. Always seek the advice of your physician or other qualified health provider with any questions you may have regarding a condition.

NASPGHAN YouTube Video for Eosinophilic Esophagitis

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NASPGHAN has developed a useful ~6 minute video for families reviewing the treatments (diet and medications) for eosinophilic esophagitis. When I visited the site, it had not garnered much traction yet (very few views). I would recommend this video to families:

NASPGHAN & GIKids -YouTube Video: Ways to Treat Eosinophilic Esophagitis (EoE)

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Briefly noted: Aerodigestive Medicine and Budesonide for Eosinophilic Esophagitis

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A shout out to Ben Gold who is a coauthor on several new publications:

A Krasaelap et al. JPGN 2023; 77: 460-467. Pediatric Aerodigestive Medicine: Advancing Collaborative Care for Children With Oropharyngeal Dysphagia

This is a terrific review of the dysphagia and the multidisciplinary approach to management. Many pearls are in this article. For example, laryngo-tracheo-esophageal cleft (LTEC), “while rare, 1 in 10,000-20,000 live births, the incidence of LTEC is higher (7.6%-22%) in children with aerodigestive issues such as a chronic cough.” [As an aside, this should be repeated given the changing population of patients being seen.]

VA Mukkada, SK Gupta, BD Gold et al. JPGN 2023; 77: 760-768. Pooled Phase 2 and 3 Efficacy and Safety Data on Budesonide Oral Suspension in Adolescents with Eosinophilic Esophagitis

Key finding: Significantly more patients who received BOS (2mg BID) than placebo achieved histologic responses (≤6 eos/hpf: 46.7% vs 6.5%; ≤1 eos/hpf: 42.2% vs 0.0%; <15 eos/hpf: 53.3% vs 9.7%; P < 0.001)

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View from Rua Augusta Arch in Lisbon

Increasing Burden of Eosinophilic Esophagitis

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AY Lam et al. Clin Gastroenterol Hepatol 2023; 21: 3041-3050. Open Access (Partial)! Epidemiologic Burden and Projections for Eosinophilic Esophagitis–Associated Emergency Department Visits in the United States: 2009-2030

Methods: Data from the US Nationwide Emergency Department Sample (NEDS) were used to estimate weighted annual EoE-associated ED visits from 2009 to 2019. Autoregressive integrated moving average (ARIMA) models were used to project EoE-associated ED visits to 2030. NEDS is a large, publicly available, all-payer ED database in the United States, approximating a 20% stratified sample of US hospital-based EDs. 

Key points:

  1. There has been a near tripling of the frequency of EoE-associated ED visits over the course of the past decade which is correlated with an increasing prevalence of EoE. The annual volume of EoE-associated ED visits increased from 2934 in 2009 to 8765 in 2019, and is projected to reach 15,445 by 2030.
  2. Without new interventions, this article projects further increases with doubling again by 2030 (using conservative estimates).
  3. Increasingly EoE is being managed without admission, though average charges associated with ED visits for EoE have tripled since 2009. Total mean inflation-adjusted charges for an EoE-associated ED visit were $9025 US dollars in 2019.
  4. Half of EoE patients presenting to the ED required an endoscopy and 40% required a foreign body/food impaction removal.

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FLIP Patterns for Adults with Eosinophilic Esophagitis

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DA Carlson et al. Gastroenterol 2023; 165: 552-563. Open Access! A PhysioMechanical Model of Esophageal Function in Eosinophilic Esophagitis

215 adults with EoE who completed FLIP during endoscopy were included in a cross-sectional study. FLIP helped separate the physiomechanical properties of esophageal function in this cohort. The criteria used to define the PhysioMechanical classification in EoE with a representative FLIP panometry image for each classification. Normal compliance was defined as a DP >17 mm and body compliance >450 mm3/mm Hg; reduced compliance (fibrostenosis) was defined by DP ≤17 mm or compliance ≤450 mm3/mm Hg. Normal EGJ opening was defined as a maximum EGJ diameter ≥16 mm; reduced as maximum EGJ diameter <16 mm. ∗Spastic-reactive contractile response (SRCR) with normal body distensibility and normal EGJ opening was assigned as “achalasia pattern” (n = 1 in this cohort).

Key findings:

  • FLIP was normal in 50 (23%), weak pattern in 7 (3%), IsoEGJOO stricture pattern in 27 (13%), IsoEGJOO achalasia pattern in 26 (12%), Fibrostenosis with normal reactivity in 61 (28%), spastic reactive fibrostenosis with normal reactivity in 30 (14%), and noreactive fibrostenosis in 14 (7%)

My take: FLIP testing helps define the mechanism of esophageal dysfunction in patients with EoE. Longer duration of symptoms was associated with more severe esophageal dysfunction.

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But How Well Does It Work in Theory and Eosinophilic Esophagitis Treatments

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C Mayerhofer et al. Clin Gastroenterol Hepatol 2023; 21: 2197-2210. Open Access! Efficacy of Elimination Diets in Eosinophilic Esophagitis: A Systematic Review and Meta-analysis

“That’s all well and good in practice… but how does it work in theory?” I saw this quote many years ago when I was visiting the University of Chicago.

This quote came to mind as I was reading this article which showed relatively little change in the efficacy between more and less stringent elimination diets for eosinophilic esophagitis. This meta-analysis included 915 children and 847 adults and assessed the efficacy rates of 4 major dietary treatment regimens in eosinophilic esophagitis: 6-food (SFED), 4-food (FFED), 1-food (OFED), and a targeted elimination diet (TED).

Key findings:

  • The overall rate of histologic remission was 53.8% and in the individual dietary groups was 61.3% for SFED, 49.4% for FFED, 51.4% for OFED, and 45.7% for TED.
  • The overall rate of clinical response was 80.8%, with response rates of 92.8% for SFED, 74.1% for FFED, 87.1% for OFED, and 69.0% for TED.
Percentage of food antigen triggers identified via endoscopic
and clinical evaluation after food re-introduction.

My take: It is clear to me that more restrictive diets can yield better response rates; however, in clinical practice they are difficult to maintain and this study shows that the improvement with more food restrictions may be quite limited.

Another reference on eosinophilic esophagitis: CJ Ketchem et al. Clin Gastroenterol Hepatol. 2023 Aug;21(9):2252-2259. Open Access! Higher Body Mass Index Is Associated With Decreased Treatment Response to Topical Steroids in Eosinophilic Esophagitis. Key finding: Histologic response (n=296) to topic steroids was higher for those who were nonobese compared with obese at fewer than 15 eosinophils per high-power field (61% vs 47%; P = .049); in addition, nonobese patients had significantly greater endoscopic and symptomatic responses.

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When to Use Dupilumab for Eosinophilic Esophagitis: Multispecialty Guidelines

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SS Aceves et al. Annals of Allergy, Asthma, and Immunology. 2023; 130: 371-378. Open Access! Clinical guidance for the use of dupilumab in eosinophilic esophagitis

This article summarizes updated recommendations for eosinophilic esophagitis from the Joint Task Force for the American Academy of Allergy Asthma Immunology and American College of Allergy Asthma Immunology and the American Gastroenterology Association (JTF-AGA). It offers a good number of recommendations regarding when using dupilumab should be considered.

Other Key Points:

  • “Dupilumab can be considered as first-line therapy in patients presenting with severe EoE”and in patients with multiple atopic diseases.
  • In addition, it recommends “performing a repeat EGD, along with obtaining biopsies, 5 to 6 months after either starting dupilumab therapy or whenever adjusting the dupilumab dose.” In some cases, like stricture dilatation, the authors indicate that earlier EGD may be appropriate.
  • The advantages/disadvantages of current treatment options are summarized in Table 3. For dupiliumab, the disadvantages include its high price of dupilumab and weekly injections. Conjunctivitis has been an adverse effect identified in its usage with other indications.

My take: Dupilumab is a major advance for patients with EoE. Due to the need for weekly injections and its costs, it is likely a 2nd line agent for most kids with EoE.

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