Tag Archives: budesonide

Misleading Study on Topical Steroids for Eosinophilic Esophagitis -Comparing Four Apples to One Apple

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FB Murray et al. Am J Gastroenterol 2026; 121: 130-139. Loss of Response to Off-Label Swallowed Topical Corticosteroids in Eosinophilic Esophagitis Can be Overcome by a Switch to an Esophageal-Targeted Budesonide Formulation

A quick glance at this study gives the impression that off-label swallowed topical corticosteroids (olSTC) are an inferior treatment to the budesonide orodispersible tablet (BOT) as many patients who had either a non-response to olSTC achieved remission with BOT.

Methods: This study from the Swiss Eosinophilic Esophagitis Cohort Study with 340 patients (mean age 43 years) analyzed prospectively collected data. Twenty-six percent had prior olSTC nonresponse (n=66) , 16% were in remission with prior olSTC (n=44), and 58% were STC-naïve.

Here were the key results according to the authors (Figure 2):

  • Histologic remission (<15 eos/hpf) was achieved in 62% who had not responded to olSTC previously and in 72% who had prior olSTC response (P=0.094)
  • The authors conclude that “our results provide conclusive evidence that off-label STC cannot be translated into corticosteroid-refractory disease per se.”

Here’s the main problem with this study:

  • “Most patients in Switzerland have been treated with a rather low-dose olSTC regimen (</ = to 0.5 mg per day).” Typical BOT dosing is 2 mg per day. Thus, the authors are comparing the use of 4-times the amount of budesonide in the BOT group to the olSTC non-responders.
  • Their discussion states that “most patients with EoE without a response to olSTC are not truly corticosteroid-refractory but respond to an esophageal adjusted topical corticosteroid formulation…In the United States, a BOS [suspension] has been recently approved…Due to similar mechanism of action, it can by hypothesized that patients without prior response to olSTC will respond to BOS in similar rates as shown in our study.” Yet, there is no proof that the formulation made a difference in this study; the more likely explanation is that patients previously who had not responded to olSTC were under-treated.

My take:

  1. In patients with eosinophilic esophagitis who have not responded to topical steroids, it is important to make sure that they were prescribed the right dose and that they are actually taking the medication.
  2. Future studies of esophageal formulations should be compared to off-label STC using the same dose to determine if the formulations confer additional benefits.
  3. Getting the right dose is important for every malady.

Thanks to Ben Gold for sharing this publication with me.

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Is Topical Budesonide Less Effective in Patients With Eosinophilic Esophagitis With Strictures?

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I Hirano et al. American Journal of Gastroenterology 2025; 120(7):p 1502-1510. Open Access! Effect of Esophageal Dilation History on Efficacy Outcomes in Patients With Eosinophilic Esophagitis Receiving Budesonide Oral Suspension

Methods: This post hoc analysis assessed data from a 12-week, randomized, double-blind, placebo-controlled phase 3 study (NCT02605837) of budesonide oral suspension (BOS) 2.0 mg twice daily in patients (n=318) aged 11–55 years with EoE and dysphagia. Coprimary efficacy outcomes were histologic (≤ 6 eosinophils per high-power field [eos/hpf]) and dysphagia symptom (≥ 30% reduction in Dysphagia Symptom Questionnaire scores from baseline) responses at week 12.

Key findings:

  • Histologic responses (≤ 6 and < 15 eos/hpf) were similar regardless of dilation history
  • Fewer BOS-treated patients with dilation history than no dilation history achieved a dysphagia symptom response (44.0% vs 59.0%)

Discussion Points:

  • “Esophageal dilation may provide immediate relief from dysphagia (15); symptom improvement has been observed in 95% of dilated patients with EoE (29)…[however] dilation does not affect the underlying inflammation (18).”
  • “A histologic response (<15 eos/hpf) to swallowed corticosteroids has also been associated with a reduced number of repeat esophageal dilations required to maintain a similar esophageal caliber compared with nonresponse (≥15 eos/hpf)…this supports swallowed corticosteroid use in patients who have undergone esophageal dilation, even in the absence of acute symptom improvement.”
  • “Study limitations include potential enrollment of patients with severe disease due to stringent inclusion criteria.”

My take: While dilatation alone often improves symptoms, treatment with budesonide may help reduce need for repeat dilatations.

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Long-Term Treatment of Eosinophilic Esophagitis with Budesonide

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The study by Dellon et al was a 4-year, phase 3, open-label study in patients with EoE who completed up to 52 weeks of BOS therapy (Budesonide oral suspension 2 mg 2/day) in 2 preceding phase 3 studies.

Key findings:

  • At month 48 of treatment, 50.0% and 58.3% of patients achieved/maintained a histologic response (< or =6 and <15 eosinophils per high-power field, respectively)

Safety:

  • Treatment-emergent adverse events (TEAEs) occurred in 76.3% of patients; most were mild/moderate in severity and unrelated to study drug.
  • The most frequently reported BOS-related TEAEs included abnormal adrenocorticotropic hormone stimulation test results (8.4%, 11/131; number of events [m] [ 12) and adrenal insufficiency (2.3%, 3/131; m [ 3). Esophageal candidiasis occurred in 3.1% of patients (4/131)

The study by Biedermann et al explored the use of an orodipsersible tablet for EoE up to 3 years in patients who achieved remission during a 12-week induction. This tablet is not available in the U.S.

Key findings:

  • At week 96, 80.1% of patients were in histologic remission, defined as peak eosinophils per high-power field of <5, at week 96 vs 91.8% at open label extension baseline
  • No new safety concerns were observed across 96 weeks of treatment. Suspected symptomatic candidiasis occurred at similar rates to prior BOT studies and was predominantly mild and resolved with treatment

My take: The pharmaceutical budesonide suspension, Eohilia, is labelled by the FDA for use as a 12 week treatment course. Since EoE is a chronic disease, 12 weeks is insufficient. These long-term studies provide data that may address this shortcoming.

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How to Best Use Steroids for Inflammatory Bowel Disease

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JD Feuerstein et al. Clin Gastroenterol Hepatol 2025; 23: 2068-2082. Open Access! Appropriate Use and Complications of Corticosteroids in Inflammatory Bowel Disease: A Comprehensive Review

Steroids are commonly used and misused for inflammatory bowel disease. This article reviews best practices, steroid formulations/dosing, and potential complications.

  • For moderate to severe ulcerative colitis (in adults), the authors recommend treatment with 40 mg of prednisone daily. Patients with ASUC (acute severe ulcerative colitis) should be treated with 60 mg of IV methylprednisolone for 3 to 5 days, after which rescue therapy should be initiated
  • Use of budesonide is recommended as an option for many clinical situations to minimize steroid adverse effects. These situations include mild-moderate UC failing to respond to mesalamine, ileal CD and older patients
  • Postoperative complications: “In the postoperative period, patients treated with CS had a higher risk of both infectious complications (aOR, 3.69; 95% CI, 1.24–10.97) and major infectious complications (aOR, 5.54; 95% CI, 1.12–27.26) [Abrerra et al].135  Subramanian pooled data from 7 studies showing that preoperative CS use is associated with increased postoperative complications (OR, 1.41; 95% CI, 1.07–1.87) as well as infectious complications.

The authors note that corticosteroids “remain widely available and are an effective short-term option for induction of remission in patients with active UC or inflammatory CD. However, their well-described and significant safety profile warrants proactive strategies to limit their use through non-systemic formulations, short-term exposures, steroid-sparing maintenance options, and most recently, complete steroid avoidance strategies.”

My take: Continuing steroids when they are not effective prior to potential surgery (eg. ASUC) remains a frequent problem. Sometimes, it is difficult to know it they are helping some.

Rectal Budesonide for Biliary Atresia After Kasai Procedure

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S Langreen et al. JPGN 2025;81:626–633. Rectal budesonide: A potential game changer after Kasai hepatoportoenterostomy

Background: After the START trial in 2014, it seemed that enthusiasm for post-operative steroids for biliary atresia had waned. The START study did not find that steroids improved outcomes after Kasai hepatoportoenterostomy (HPE). Subsequently, though, there have been observational reports of using steroids in a customized fashion to improve outcomes. Langreen et al add to this literature by examining their use of rectal budesonide (2 mg) for 3 months in a retrospective cohort (n=142) with a historical control (n=137). Jaundice-free native liver survival (jfNLS) was assessed at 6 months, 2 years, 5 years, and 10 years post-Kasai.

Key findings:

  • Improvements were noted in jfNLS at 6 months (53% vs. 39%) , 2 years (45% vs. 22%), 5 years (40% vs. 23%) and 10 years (32% vs. 13%)
  • These benefits were exclusive to patients with nonsyndromic BA
  • No serious adverse effects were identified with budesonide

Rationale for rectal budesonide: The authors note that “a single dose of budesonide foam contains about 2 mg of budesonide, equivalent to 25 mg of prednisolone or 20 mg of methylprednisolone…In our series, no serious steroid associated adverse effects were recorded, possibly due to the first pass after rectal administration.”

Limitations: “The retrospective nature of our data analysis allows for variability in the follow‐up protocols, potential biases (historical control group, change of surgeons) and confounding factors cannot be entirely ruled out.”

Kaplan–Meier curve comparing native liver survival between the study and control groups
over a 10‐year follow‐up.. Study group—blue. Control group—orange.

My take: The START study with 140 participants was well-designed and did not find a benefit with systemic steroids. However small differences in outcomes can be difficult to identify. Rectal budesonide may improve outcomes. A randomized, double-blind, placebo-controlled trial would be more definitive.

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Budesonide Tablet vs Off-Label Corticosteroids in Eosinophilic Esophagitis

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G Pellegatta et al. Clin Gastroenterol Hepatol 2025; 23: 1058-1060. Open Access! Switch From Off-Label Swallowed Topical Corticosteroids to Budesonide Orodispersible Tablets in Eosinophilic Esophagitis Patients

Methods: This was a single center, prospective, observational study with adult patients previously diagnosed with EoE. Thirty EoE patients, receiving off-label swallowed topical corticosteroids (STCs), were consecutively enrolled. “This is the first study to evaluate the clinical, histological, and endoscopic efficacy of the switch from STCs to BOT [Budesonide Orodispersible Tablet]”

Key findings:

  • The median Dysphagia Symptoms Score decreased from 5 (range 0–9) under STCs therapy to 0 (range 0–6) under BOT therapy (P < .0001)
  • After switching to BOT, there was a significant increase in the number of patients in histological remission (STCs: n = 19 of 30 [63.3%] vs BOT: n = 27 of 30 [90%]; P = .030) and histological deep remission (STCs: n = 17 of 30 [56.6%] vs BOT: n = 25 of 30 [83.3%]; P = .047) 
  • Another important improvement following the switch was the improved patient satisfaction with the therapy in terms of a faster and easier modality of assumption…favors a better compliance to BOT
  • There was a “slight increase in oral Candida infection after BOT”

The authors did not include any cost information regarding the switch. In U.S., BOT is not an available treatment option. However, Eohilia, which is a budesonide suspension with a 12-week FDA approval period, costs ~$2100 per month (for 600 mL =30 day supply), whereas budesonide ampules at same dosage cost ~$300 per month (60 1 mg ampules).

My take: BOT therapy, which was targeted for esophageal delivery, was associated with better response rates. However, the cost of targeted FDA approved budesonide therapy in U.S, is exorbitant.

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Key Advances in 2024: An Overview from GutsandGrowth (Part 2)

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This year I had the opportunity to give a lecture to our group that reviewed much of the important advances that happened in 2024. Here are some of the slides (if you have any trouble reading the slides, you can search for the original blog post using author name).

Delivery Vehicle and Outcomes for Budesonide-Treated Eosinophilic Esophagitis

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N Lendner, et al. J Pediatr Gastroenterol Nutr. 2024;79:92‐99. Comparison of budesonide vehicles in inducing histologic remission in pediatric eosinophilic esophagitis.

This retrospective study with 111 patients with EoE examined histologic remission with oral viscous budesonide (OVB) and various delivery vehicles (Splenda, honey, syrup or applesauce). Key findings:

  • Overall rate of histologic remission with OVB was 52.6% (“which is less than the reported response of approximately 66% for topical steroid therapy”).
  • There was no difference in rates of histologic remission or response in mid and distal esophagus, respectively) among the different vehicle types or treatment regimens. Similarly, there was no difference in endoscopic remission or response

My take: It does not seem to matter which delivery vehicle is used for OVB; thus, clinicians should aim for more palatable and cost‐effective vehicles.

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Budesonide FDA-Approved for Eosinophilic Esophagitis

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AAP News 2/13/24: FDA approves first oral therapy for EoE

Eohilia is given in doses of 2 milligrams twice a day for 12 weeks. The label notes it has not been shown to be safe and effective for longer.

The FDA accepted Takeda’s new drug application in December 2020. A year later, the FDA determined more study was needed. Takeda revised its application and resubmitted it in September 2023.

Takeda conducted two multicenter, randomized, placebo-controlled trials in patients 11 to 56 years and 11 to 42 years, respectively. The first found 53% of the treatment group achieved histologic remission compared to 1% receiving a placebo. The second found 38% of the treatment group achieved remission vs. 2% of the placebo group, according to Takeda…

Patients [need] to refrain from eating or drinking for at least 30 minutes after taking Eohilia. After 30 minutes, patients should rinse their mouth and spit to reduce the risk of developing thrush.

My take: Budesonide has been used effectively for EoE for a long time; it is good news that it is recognized by FDA with a specific EoE indication. However, it is a little concerning that the label indication is for 12 weeks when we know that this is chronic disease. Also, I am eager to see how much this formulation costs in comparison to the budesonide ampules.

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Is It a Mistake to Use Budesonide for Autoimmune Hepatitis?

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A Diaz-Gonzalez et al. Hepatology 2023; 77: 1095-1105. Open Access! Budesonide as first-line treatment in patients with autoimmune hepatitis seems inferior to standard predniso(lo)ne administration

Background: AASLD guidelines also suggest the use of budesonide with azathioprine as an alternative agent (to prednisone with azathioprine) in patients without cirrhosis or a severe acute presentation.1–3 However, particularly in pediatrics, there is concern that it is not as effective.

Methods: This was a retrospective, multicenter study of 105 naive AIH patients treated with budesonide as the first-line drug. The control group included 276 patients treated with prednisone.

Key findings:

  • The biochemical response (BR) rate was significantly higher in patients treated with prednisone (87% vs. 49% of patients with budesonide, p < 0.001). BR was defined as normalization of both serum transaminases and IgG.
  • The probability of achieving BR was significantly lower in the budesonide group (OR = 0.20) at any time during follow-up, and at 6 (OR = 0.51) and 12 months after starting treatment (0.41)
  • Prednisone treatment was significantly associated with a higher risk of adverse events (24.2% vs. 15.9%). These differences vanished when patients with cirrhosis were excluded from the analysis, showing a similar incidence of AEs in both groups (p = 0.119). Of the specific adverse effects, only the presence of osteoporosis was significantly higher in the prednisone group (mainly in those older than 60 years)
  • The authors note that budesonide was “only indicated in 5.4% of patients newly diagnosed with AIH… Budesonide was mainly employed in patients with low baseline transaminases, suggesting that this drug is preferred in patients with less severe disease.”

My take: “The use of budesonide in the real-life setting was low and was associated with a lower probability of achieving BR with respect to prednisone.” It likely needs to be restricted to those with mild disease, and those with adverse events with prednisone. Cost is less of an issue as budesonide can be obtained as a generic (Mark Cuban Costplus pharmacy: Budesonide).

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