Tag Archives: eosinophilic gastritis

Eosinophilic Gastritis -Pathogenesis Is Not Just the Eosinophils or Benralizumab Would Work

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KL Kliewer et al. Lancet Gastroenterol Hepatol 2023; 8: 803–15. Benralizumab for eosinophilic gastritis: a single-site, randomised, double-blind, placebo-controlled, phase 2 trial

Background/Methods:  Benralizumab is an eosinophil-depleting monoclonal antibody that targets the interleukin-5 receptor α. This was a “single-site, randomised, double-blind, placebo-controlled, phase 2 trial at Cincinnati Children’s Hospital Medical Center (Cincinnati, OH, USA). Individuals aged 12–60 years with symptomatic, histologically active eosinophilic gastritis (peak gastric eosinophil count ≥30 eosinophils per high-power field [eos/hpf] in at least five hpfs) and blood eosinophilia (>500 eosinophils per μL [eos/μL]) were randomly assigned (1:1, block size of four) to benralizumab 30 mg or placebo.” 26 patients were enrolled.

Key findings:

  • Improved eosinophil counts: Changes from baseline to week 12 were significantly greater in the benralizumab group versus the placebo group for peak gastric eosinophil counts (mean –137 eos/hpf [95% CI –186 to –88] vs –38 eos/hpf [–94 to 18]; p=0·0080)
  • Patients were followed up to 88 weeks in open-label extension periods. Even though banalizumab depleted eosinophils in the blood and gastric tissue in most patients, there was minimal effect on the structural histological abnormalities, endoscopic severity, and gene expression profile compared with placebo.

My take: To improve eosinophilic gastritis will require more than targeting eosinophils. In addition, eosinophil counts are not a reliable marker for improvement in this disorder. This also suggests that eosinophil counts are not reliable as a stand-alone biomarker in other eosinophilic gastrointestinal disorders.

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Near Salt Lake City

Updated Nomenclature for Eosinophilic Gastrointestinal Diseases

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ES Dellon et al. Clin Gastroenterol Hepatol 2022; 20: 2474-2484. Open Access! International Consensus Recommendations for Eosinophilic Gastrointestinal Disease Nomenclature

This article has 91 authors! Using Delphi surveys, the authors recommend the following:

  • “EGID” was the preferred umbrella term for disorders of gastrointestinal (GI) tract eosinophilic inflammation in the absence of secondary causes
  • Involved GI tract segments will be named specifically and use an “Eo” abbreviation convention: eosinophilic gastritis (now abbreviated EoG), eosinophilic enteritis (EoN), and eosinophilic colitis (EoC)
  • For EoN, “it is desirable, but not required, to name specific locations of small bowel involvement, if these are known…The abbreviation for eosinophilic duodenitis should be “EoD”… for eosinophilic jejunitis should be “EoJ”….eosinophilic ileitis should be “EoI”
  • The term “eosinophilic gastroenteritis” is no longer preferred as the overall name (but can be used to indicate involvement of both the stomach and small bowel)
  • When >2 GI tract areas are involved, the name should reflect all of the involved areas

Endoscopic Assessment of Eosinophilic Gastritis

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I Hirano et al. Am J Gastroenterol 2022; 117: 413-423. Prospective Endoscopic Activity Assessment for Eosinophilic Gastritis in a Multisite Cohort Thanks to Ben Gold for this reference.

Methods: Endoscopic features were prospectively recorded (n=65) using a system specifically developed for EG, the EG Endoscopic Reference System (EG-REFS)

Key findings:

  • The most common endoscopic findings were erythema (72%), raised lesions (49%), erosions (46%), and granularity (35%); only 8% of patients with active histology (≥30 eosinophils/high-power field) exhibited no endoscopic findings
  • A strong correlation between EG-REFS scores and physician global assessment of endoscopy severity was demonstrated (Spearman r = 0.84, P < 0.0001)
  • EG-REFS severity was significantly correlated with active histology, defined by a threshold of ≥30 eosinophils/high-power field (P = 0.0002).

My take: This reference has a ton of terrific pictures (48 for Figure 1) which showcase the wide variety of endoscopic findings (unfortunately these are behind a paywall). Overall, the study lays the groundwork for scoring the severity of EG and for serial assessments.

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 Ristras are the strings of chile you see hanging along fences,
on patios and on portals all over New Mexico

Two Studies for Eosinophiles

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ES Dellon et al. Clin Gastroenterol Hepatol 2022; 20: 535-545. Open Access: Determination of Biopsy Yield That Optimally Detects Eosinophilic Gastritis and/or Duodenitis in a Randomized Trial of Lirentelimab

Key findings:

  • GI eosinophilia was patchy and that examination of multiple biopsies was required for diagnosis—an average of only 2.6 per 8 gastric biopsies and 2.2 per 4 duodenal biopsies per subject met thresholds for EG/EoD.
  • Evaluation of multiple nonoverlapping hpfs in each of 8 gastric and 4 duodenal biopsies was required to capture 100% of EG/EoD cases.

The 2nd article’s abstract was posted on this blog in July 2020 (Phase 3 Trial of Budesonide for Eosinophilic Esophagitis). Here is the published citation and graphical abstract:

I Hirano et al. Clin Gastroenterol Hepatol 2022; 20: 525-534. Open Access: Budesonide Oral Suspension Improves Outcomes in Patients With Eosinophilic Esophagitis: Results from a Phase 3 Trial

New Treatment for Eosinophilic Gastritis and Duodenitis

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ES Dellon et al. NEJM 2020; 383: 1624-1634. Anti–Siglec-8 Antibody for Eosinophilic Gastritis and Duodenitis

Background: AK002 (lirentelimab) is an anti-Siglec-8 antibody that depletes eosinophils and inhibits mast cells.

Methods: In this phase 2 trial, the authors randomly assigned adults (n=65) who had symptomatic eosinophilic gastritis, eosinophilic duodenitis, or both conditions in a 1:1:1 ratio to receive four monthly infusions of low-dose AK002, high-dose AK002, or placebo

Key findings:

  • The mean percentage change in gastrointestinal eosinophil count was −86% in the combined AK002 group, as compared with 9% in the placebo group
  • Treatment response  (>30% reduction in total symptom score and >75% reduction in gastrointestinal eosinophil count) occurred in 63% of the patients who received AK002 and in 5% of the patients who received placebo
  • The authors note that AK002 “also resulted in alleviation of dysphagia in patients with a history of concomitant eosinophilic esophagitis.”
  • Limitations: Small study and 10% developed antibodies to drug

My take: Larger phase 3 studies with AK002 are underway (NCT04322604 & NCT04322708). AK002 looks promising for eosinophilic gastrointestinal diseases.

Change in total symptom score over 14 weeks. “Shown is the least-squares mean percentage change from baseline in total symptom score over time.” The total symptom score ranges from 0 to 80, with higher scores indicating greater symptom severity. Each of eight symptoms are given a score of 0 to 10: abdominal pain, nausea, vomiting, early satiety, loss of appetite, abdominal cramping, bloating and diarrhea.

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#NASPGHAN19 Selected Abstracts (Part 2)

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Link to full NASPGHAN 2019 Abstracts.

Here are some more abstracts/notes that I found interesting at this year’s NASPGHAN meeting.

A study (poster below) from Cincinnati found that a vedolizumab level ≥34.8 mcg/mL at week 6 (prior to 3rd infusion) predicted clinical response at 6 months

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The poster below reported a high frequency of eosinophilic disorders in children who have undergone intestinal transplantation. Related blog post: Eosinophilic disease in children with intestinal failure

This study from Boston indicates that acid suppression was not associated with improved outcomes in infants with laryngomalacia (eg. lower supraglottoplasy rates or lower aspiration rates.

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The study below showed that “less than half of children who started the low FODMAP diet were able to complete the elimination phase.” This indicates the need for careful dietary counseling when attempting this therapy.

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The abstract below showed that the dietary intake of children with inflammatory bowel disease, who were not receiving enteral nutrition therapy, was similar to healthy control children.

The next two studies provide some pediatric experience with tofacitinib in teenagers with inflammatory bowel disease (14-18 years of age).  The first poster had 12 children and reported a 67% clinical response rate (cohort with 5 with CD, 5 with UC, and 2 with IC).  The second poster had 4 of 6 with a clinical response and 3 in remission.

Related blog posts -Tofacitinib:

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.

#NASPGHAN19 Postgraduate Course (Part 5)

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Here are some selected slides and notes from this year’s NASPGHAN’s postrgraduate course.  There may be errors in omission or transcription on my part.

Link to the full NASPGHAN PG Syllabus 2019 (Borrowed with permission)

– Intestinal Inflammation Session

192 David T. Rubin, MD, University of Chicago Positioning the new IBD therapies: Merging experience with evidence

Some key points:

  • Ustekinumab escalation can increase response. Optimization in CD patients with loss of response led to recapture of response in 69% of patients
  • Tofacitinib –given black warning, will likely be used in more refractory patients
  • May be able retry a previous therapy (Chicago protocol in slide below)

As an aside, while Dr. Rubin is an excellent speaker, my view is that there are so many terrific pediatric IBD specialists, I would favor having a pediatric IBD specialist give this talk at our postgraduate course.  (Some might argue that adult IBD specialists would have more experience with emerging therapies.)

204 Anne Griffiths, MD, FRCPC, Hospital for Sick Children Immunosuppressive therapy in IBD: Can we de-escalate therapy?

  • High rate of relapse when biologic therapy is stopped.  Use of an immunomodulator may reduce the relapse rate when stopping an anti-TNF agent

215 Stacy Kahn, MD, Boston Children’s Hospital When it is not IBD … rare forms of intestinal inflammation

  • For patients with milder microscopic colitis, antidiarrheal agents can be given.  For more severe disease, budesonide is effective.

223 Edaire Cheng, MD, UT Southwestern Medical Center  Eosinophilic inflammation beyond the esophagus

 

Disclaimer: NASPGHAN/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. The discussion, views, and recommendations as to medical procedures, choice of drugs and drug dosages herein are the sole responsibility of the authors. Because of rapid advances in the medical sciences, the Society 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. Some of the slides reproduced in this syllabus contain animation in the power point version. This cannot be seen in the printed version.

Epidemiology of Eosinophilic Disorders

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Jensen et al. JPGN 2016; 62: 36-42.  The researchers used a large database (>75 million individuals) representative of US commercially-insured population to provide estimates of the prevalence of several eosinophilic disorders:

  • Eosinophilic gastritis 6.3 per 100,000
  • Eosinophilic gastroenteritis 8.4 per 100,000
  • Eosinophilic colitis 3.3 per 100,000

In the associated commentary by Furuta et al (pg 1), clinicians are encouraged to urge patients with EGID to register on the Consortium for Eosinophilic Gastrointestinal Disease Research registry: https://www.rarediseasesnetwork.org/cms/CEGIR

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Screen Shot 2016-02-01 at 6.25.41 PM

 

Eosinophilic Esophagitis Review -NEJM

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Good review:  Glenn T. Furuta, M.D., and David A. Katzka, M.D. N Engl J Med 2015; 373:1640-1648

A couple pointers from this review:

  • Estimated prevalence of eosinophilic esophagitis (EoE) 0.4% in Western countries.  Symptoms are often underestimated due to patient ‘accommodation’ which includes eating slowly/carefully, drinking a lot of liquids and avoiding items more prone to become lodged (meats, pills, breads)
  • Pathogenesis: “Birth by cesarean section, premature delivery, antibiotic exposure during infancy, food allergy, lack of breast-feeding, and living in an area of lower population density have all been associated with eosinophilic esophagitis.”
  • Impaired barrier function and enhanced the activity play a role in pathogenesis
  • Food allergy is a non-IgE-mediated process.  Omalizumab, an anti-IgE biologic, is ineffective in EoE and EoE can develop in IgE-null mice
  • Male predominance (3:1) suggests that there is a genetic component.

Esophagus with ringed appearance, furrowing, and loss of vascular markings

Esophagus with ringed appearance, furrowing, and loss of vascular markings

Another useful reference on Eosinophilic Gastritis in Children: Am J Gastroenterol 2014; 109; 1277-85.  This article provides data on clinical and histologic remission with eosinophilic gastritis (>70 eos/hpf), n=30 children.  “Response to dietary restriction was high” (82% clinical, 78% histologic response) Thanks to Seth Marcus for this reference.

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Useful Information on Eosinophilic Disorders

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A review (JB Wechsler et al. J Asthma Allergy 2014; 7: 85-94) provides practical advice on dietary management of eosinophilic esophagitis (EoE); the section on food reintroduction from elemental diets for patients with EoE is particularly helpful.  They start with typically less allergenic foods (group A) to most allergenic (group D) -from their Table 2:

Group A:

  • Vegetables (nonlegume): carrots, squash, sweet potato, white potato, string beans, broccoli, lettuce, beets, asparagus, cauliflower, Brussel sprouts
  • Fruit (noncitrus, nontropical) apples, pear, peaches, plum, apricot, nectarine, grape, raisins
  • Vegetables: tomatoes, celery, cucumber, onion, garlic, and other vegetables

Group B

  • Citrus fruit: orange, grapefruit, lemon, lime
  • Tropical fruit: banana, kiwi, pineapple, mango, papaya, guava, avocado
  • Melons: honeydew, cantaloupe, watermelon
  • Berries: strawberry, blueberry, raspberry, cherry, cranberry

Group C

  • Legumes: lima beans, chickpeas, white/black/red beans
  • Grains: oat, barley, rye, other grains
  • Meat: lamb, chicken, turkey, pork

Group D

  • Fish/shellfish
  • Corn
  •  Peas
  • Peanut
  • Wheat
  • Beef
  • Soy
  • Egg
  • Milk

Also, this review includes a long list of “freebie” foods allowed while on elemental diet, including artificial flavors/colors, corn syrup, oils, salt, crystal lite, and many others.

The authors note that “in our practice, the period of exclusive elemental formula is limited to 4 weeks prior to therapeutic assessment by endoscopy and reintroduction…Single foods are introduced every 5-7 days” within a group and then endoscopy after 3-4 foods are clinically tolerated.”  Foods from groups C and D are introduced more cautiously.

Also noted: HM Ko et al. Am J Gastroenterol 2014; 109: 1277-85.  This retrospective study of 30 children with severe gastric eosinophilia (mean age 7.5 years) provides a good deal of useful information.  Key point: “the disease is highly responsive to dietary restriction therapies.”  82% of patients responded to dietary restrictions and 78% had a histologic response as well.  Dietary treatments included amino acid-based diet in 6 (n=6), 7-food group empiric diet (n=6), and empiric avoidance of 1-3 foods (n=5).  Pharmacologic treatments (proton pump inhibitor or cromolyn) were attempted in a total of four patients in this series with half responding clinically and one of four responding histologically.

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Disclaimer: These blog posts are for educational purposes only. Specific dosing of medications/diets (along with potential adverse effects) should be confirmed by prescribing physician/nutritionist.  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.