New 2020 Eosinophilic Esophagitis Guidelines

Full text (I Hirano et al. Gastroenterol 2020; 158: 1776-86)AGA Institute and the Joint Task Force on Allergy-Immunology Practice Parameters Clinical Guidelines for the Management of Eosinophilic Esophagitis

Full text: PDF

This guideline was developed through a collaboration between AGA and the Joint Task Force for Allergy-Immunology Practice Parameters, which comprises the American Academy of Allergy, Asthma & Immunology and the American College of Allergy, Asthma & Immunology. This guideline is jointly published in Gastroenterology and Annals of Allergy, Asthma and Immunology.

Technical review article (MA Rank et al. Gastroenterol 2020; 158: 1789-1810): Technical Review on the Management of Eosinophilic Esophagitis: A Report From the AGA Institute and the Joint Task Force on Allergy-Immunology Practice Parameters


Link: Clinical Decision Support Tool

Link: Treatment of EoE Spotlight Poster

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Using Less Steroids for Autoimmune Hepatitis

A recent retrospective study (S Pape et al. Clin Gastroenterol Hepatol 2019; 17: 2068-75) with 451 adults (1978-2017) examined outcomes among patients based on steroid dosing.

A high-dose group (n=281) with initial prednisone/prednisolone dose of ≥0.5 mg/kg/day was compared with a low dose group (n=170) <0.5 mg/kg/day.  The low dose group had higher rates of cirrhosis (25.9% vs. 15.3%) but lower median ALT values (7.1 ULN vs. 13.4 ULN) and lower median bilirubin values (48 vs 29 micromol/L).

Key findings:

  • There was no difference in rates of transaminase normalization at 1 year: 76.2% vs 77.6%
  • Transaminase normalization was lower in patients with cirrhosis 58.1% compared to 70.7% with cirrhosis
  • Most patients were receiving low-dose steroids at 6 months, 87.4% in high-dose group compared to 83.5% in low-dose group
  • Cumulative steroid dose was lower in low-dose group, with median of 2573 mg over 6 months compared to 3780 mg

Though, not studied in this report, AASLD has recommended use of immunoglobulin levels may help with immunosuppression titration. The editorial (pg 1948-49) notes that budesonide is another alternative for AIH without cirrhosis, though “long-term outcomes including histologic remission and appropriate tapering strategy for budesonide are currently lacking.”

My take: Particularly in patients without severe inflammation, lower steroid doses can be considered for autoimmune hepatitis.

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Toronto Consensus Guidelines for Luminal Crohn’s Disease

The recommendations from the Canadian Association of Gastroenterology for luminal Crohn’s Disease in adults were published in two journals.  R Panaccione et al. Clin Gastroenterol Hepatol 2019; 17: 1680-1713 and R Panaccione et al . 2019 Aug; 2(3): e1–e34.

Full text link : Canadian Association of Gastroenterology Clinical Practice Guideline for the Management of Luminal Crohn’s Disease

A few of the 41 statement recommendations:

  • 6. In patients with mild to moderate ileal and/or right colonic Crohn’s disease, we suggest oral budesonide beginning at 9 mg/day as first-line therapy to induce complete remission. GRADE: Conditional recommendation, low-quality evidence
  • 20. In patients with moderate to severe luminal Crohn’s disease with risk factors of poor prognosis, we recommend anti-TNF therapy (infliximab, adalimumab) as first-line therapy to induce complete remission. GRADE: Strong recommendation, moderate-quality evidence
  • 23. In patients with active Crohn’s disease, when starting anti-TNF therapy, we suggest it be combined with a thiopurine or methotrexate over monotherapy to improve pharmacokinetic parameters. GRADE: Conditional recommendation, very low-quality evidence for infliximab, very low-quality evidence for adalimumab
  • 29. We suggest against switching between anti-TNF therapies in patients who are doing well on anti-TNF therapy. GRADE: Conditional recommendation, low-quality evidence
  • 30. In patients with moderate to severe Crohn’s disease who fail to achieve complete remission with any of corticosteroids, thiopurines, methotrexate, or anti-TNF therapy, we recommend vedolizumab to induce complete remission. GRADE: Strong recommendation, moderate-quality evidence
  • 34. In patients with moderate to severe Crohn’s disease who fail to achieve complete remission with any of corticosteroids, thiopurines, methotrexate, or anti-TNF therapy, we recommend ustekinumab to induce complete remission. GRADE: Strong recommendation, moderate-quality evidence
  • 37-41: Authors against the use of probiotics, omega-3 fatty acids, marijuana, naltrexone and enteral nutrition/diet therapies.

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Head-to-Head: Budesonide vs Fluticasone for Eosinophilic Esophagitis

A recent double-blind, double-dummy study (ES Dellon et al. Gastroenterol 2019; 157: 65-73) found similar efficacy between budesonide and fluticasone for newly-diagnosed eosinophilic esophagitis. They had hypothesized that an oral viscous budesonide would be more effective due to increased esophageal contact time.

Methods: The authors compared an oral viscous budesonide OVB) at 1 mg BID (n=56) to fluticasone (swallowed) MDI dosed at 880 mcg BID (n=55).  Patients aged 16-80 years, with mean of 37 years.

Baseline characteristics:

  • ~95% in both groups with dysphagia
  • ~75% with any atopic condition
  • ~50% with dilatation required at baseline

Key findings:

  • Similar drop in eosinophil count: 73 (OVB) and 77 (MDI) eos/hpf at baseline to 15 and 21 respectively
  • Histologic response (<15 eos/hpf) rates of 71% (OVB) and 64% (MDI).
  • Response to <5 eos/hpf occurred in 61% OVB and 49% MDI; response to <1 eos/hpf was noted in 41% and 35% respectively
  • Symptom scores (DSQ) responded similarly as well
  • Similar degree of candidiasis 12% for OVB and 16% for MDI

In the associated editorial, the authors speculate that one reason for similar efficacy was the detailed instructions given for patients taking the MDI.

My take: This study supports both topical steroid therapies; practical issues like cost and insurance coverage could be influential in selecting the specific treatment for an individual patient.

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From AGA twitter feed

Orodispensable Budesonide Tablets for Eosinophilic Esophagitis

Full Text Link (courtesy of AGA twitter feed):Efficacy of Budesonide Orodispersible Tablets as Induction Therapy for Eosinophilic Esophagitis in a Randomized Placebo-Controlled Trial  AJ Lucendo et al. Gastroenterol 2019; 157: 74-86.


Background & Aims

Swallowed topical-acting corticosteroids are recommended as first-line therapy for eosinophilic esophagitis (EoE). Asthma medications not optimized for esophageal delivery are sometimes effective, although given off-label. We performed a randomized, placebo-controlled trial to assess the effectiveness and tolerability of a budesonide orodispersible tablet (BOT), which allows the drug to be delivered to the esophagus in adults with active EoE.


We performed a double-blind, parallel study of 88 adults with active EoE in Europe. Patients were randomly assigned to groups that received BOT (1 mg twice daily; n = 59) or placebo (n = 29) for 6 weeks. The primary end point was complete remission, based on clinical and histologic factors, including dysphagia and odynophagia severity ≤2 on a scale of 0–10 on each of the 7 days before the end of the double-blind phase and a peak eosinophil count <5 eosinophils/high power field. Patients who did not achieve complete remission at the end of the 6-week double-blind phase were offered 6 weeks of open-label treatment with BOT (1 mg twice daily).


At 6 weeks, 58% of patients given BOT were in complete remission compared with no patients given placebo (P< .0001). The secondary end point of histologic remission was achieved by 93% of patients given BOT vs no patients given placebo (P < .0001). After 12 weeks, 85% of patients had achieved remission. Six-week and 12-week BOT administration were safe and well tolerated; 5% of patients who received BOT developed symptomatic, mild candida, which was easily treated with an oral antifungal agent.

Surprising Findings in Prospective Budesonide-Eosinophilic Esophagitis Study

A recent study (ES Dellon et al Clin Gastroenterol Hepatol 2019; 17: 666-73) prospectively followed patients in a 24 week open-label extension of a randomized, double-blind, placebo-controlled trial of budesonide oral suspension (BOS) for eosinophilic esophagitis (EoE). The authors defined histologic response as ≤6 eos/hpf. During the extension, the dosage of BOS was reduced from 2 mg twice daily to 2 mg once a day.

Key findings:

  • No new safety signals. One patient in placebo/BOS arm (n=37) developed oral candidiasis and one patient in the BOS/BOS arm (n=45) did as well. In addition, four patients in placebo/BOS developed esophageal candidiasis. No clinically relevant changes in morning serum cortisol levels were identified.
  • Histologic response was observed in 49% (16/33) in placebo/BOS arm and 23% (9/39) of BOS/BOS arm. 58% of placebo/BOS and 28% of BOS/BOS patients had ≤15 eos/hpf.
  • Mean peak eosinophil count decreased in placebo/BOS arm from 119 to 29 and increased in BOS/BOS arm from 38 to 72.
  • Overall, only 42% of patients who responded to BOS during double-blind 12 week study maintained a histologic response.

While this study shows that BOS is effective for many patients with EoE, it also shows that many lose a response.  In addition, most patients who “did not respond to treatment during the double-blind phase did not gain a histologic or endoscopic response with longer-term treatment.”  Only 1 of 26 patients (4%) gained a response. This has several important implications:

  • Some patients may develop corticosteroid resistance
  • In patients who respond to induction, it may be prudent to continue with the same induction dose rather than reducing the dosage
  • In patients who do not respond to induction, further treatment is not beneficial

My take: Though the response to BOS was not very high in this study, the population studied was highly symptomatic and had histologically-severe EoE.  Thus, in a more typical population of patients with EoE, the response rate is likely to be more favorable. Also, many patients will not maintain a response to BOS at a lowered dose.

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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.

A Better Budesonide for Eosinophilic Esophagitis (Part 2)

A recent study (ES Dellon et al Gastroenterol 2017; 152: 776-86) provides more data indicating that a premixed solution of budesonide improves eosinophilic esophagitis (EoE). This study complements a recent report highlighted in a blog post earlier this year:

A Better Budesonide for Eosinophilic Esophagitis

In the present study by Dellon et al, the authors performed a multicenter, randomized, double-blind, placebo-controlled, parallel-group trial of 93 EoE patients (ages 11-40).  All patients had dysphagia and active EoE. The active treatment group received 2 mg twice daily.

Key findings:

  • Dysphagia symptom questionnnaire (DSQ) scores improved more in the active treatment group compared to placebo.  At baseline, the DSQ scores were 29.3 and 29.0 respectively.  After 12 weeks, the the scores were 15.0 and 21.5 respectively.
  • Similarly, the active treatment group peak eosinophil counts improved more.  At baseline, the treatment group had a count (per hpf) of 156 and this dropped to 39; in contrast, the placebo group started at 130 and dropped to 113.
  • The overall histologic response (≤6 eos/hpf) was 39% for the treatment group and 3% for the placebo group.
  • No significant adverse effects could be attributed to budesonide.  There was 1 case of esohageal candidiasis.  “There were no notable differences between the groups in cortisol levels.”

My take: Budesonide suspension is useful for EoE but not effective in all patients. A reliable composition from a manufacturer, if not too expensive, would be a big improvement for many kids with EoE. Higher doses of budesonide may be warranted in some cases of EoE.

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