ES Dellon et al. Clin Gastroenterol Hepatol 2022; https://doi.org/10.1016/j.cgh.2022.02.013 (Ahead of print) Open Access: Fluticasone Propionate Orally Disintegrating Tablet (APT-1011) for Eosinophilic Esophagitis: Randomized Controlled Trial

Methods: In this randomized, double-blind, placebo-controlled, dose-finding, phase 2b trial, 106 adults with EoE received 1 of 4 APT-1011  (fluticasone propionate oral disintegrating tablet) doses or placebo for a 12-week induction period and 40 weeks of maintenance. 

Key findings:

• Histologic response (≤6 eosinophils per high-power field at Week 12) rates were 0% for placebo, 80% for APT-1011 3 mg twice daily (BID), 67% for 3 mg at bedtime (HS), 86% for 1.5 mg BID, 48% for 1.5 mg HS (P < .001 for all groups vs placebo). 
• There was also improvement in treatment group in dysphagia and EoE Endoscopic Reference Score (EREFS); the EREFS improved from 4.5 to 2.3 for 3 mg BID, 5.3 to 2.1 for 3 mg HS, 4.6 to 1.7 for 1.5 mg BID, 5.3 to 2.9 for 1.5 mg HS vs 5.2 to 4.5 for placebo. See Figure 2 for 52 week trend in EREFS.
• Candidiasis: For the 3-mg BID group, oral and esophageal candidiasis was 40% in Part 1 and 32% in Part 2, 18% and 16% for 1.5 mg BID, and 5% and 7% for 3 mg HS (same subject)
• Low morning cortisol noted 3 times in part 1 and 5 times in part 2. “All cortisol test abnormalities resolved upon retesting, with no dose adjustment or interruption of treatment.” Adrenal suppression is expected to be low because “FP undergoes extensive first-pass metabolism to inactive metabolites, with bioavailability demonstrated as <1%”

My take: A fluticasone ODT would represent a big improvement compared to current situation of asking families to either spray a pulmonary inhaler down their throat or to create a budesonide slurry using either honey or splenda. How much would this cost?

Related blog posts:

• Surprising Findings in Prospective Budesonide-Eosinophilic Esophagitis Study
• Higher Doses of Topical Steroids for Eosinophilic … – gutsandgrowth
• Genetic Basis of EoE
• Expecting Change in EoE Treatment
• 4-14-4 Rule: More Biopsies Recommended for EoE
• 2020 Eosinophilic Guidelines (AGA)
• Eosinophilic Esophagitis -FAQs
• What Happens When Topical Steroids Are Stopped in EoE?
• How Genetics Influence Response to PPIs in Eosinophilic Esophagitis

E Safroneeva et al. Clin Gastroenterol Hepatol 2022; 20: 766-775. Long-Lasting Dissociation of Esophageal Eosinophilia and Symptoms After Dilation in Adults With Eosinophilic Esophagitis

100 adults enrolled in a multisite prospective observational study in which 55 underwent dilatation. Key findings:

• In nondilated patients, the association between eos/hpf and symptoms was moderate (ρ = 0.49; P < .001) based on the symptom-based EoE activity index (EEsAI); for a 10-eos/hpf increase, the predicted EEsAI increased by 2.69 (P = .002)
• In patients dilated 1 or less and more than 1 year before index endoscopy, this association was abolished (ρ = -0.38; P = .157 for ≤1 y and ρ = 0.02; P = .883 >1 y)

Limitations: sample size (only 25% subset of total cohort due to missing data), cross-sectional study design

My take: This finding is a double-edge sword. The good part is that dilatation improves dysphagia despite ongoing inflammation which may be refractory to current medical treatments. The bad part is this dissociation in symptoms makes it less likely for patients to be adherent to therapy.

EJ Rourke. NEJM 2022; 386: 1293-1295. Open Access: Ten Years of Choosing Wisely to Reduce Low-Value Care

Key points from this commentary:

• “Let me say at the outset that in my primary care clinic I practice low-value care. Not every day, but often enough. Probably every week”
• “Choosing Wisely was an immediate public relations win for the medical profession in 2012, demonstrating that doctors were stepping up to address low value and high costs in medicine. Ten years later, however, it’s clear that making lists and publicizing them are not sufficient to reduce low-value care.¹ “
• “In the years since Choosing Wisely lists were first released, researchers have noted that specialty societies rarely select income-generating treatments provided by their members for inclusion on the lists.⁴“
• “In short, Choosing Wisely has allowed doctors (and medical societies) to look like they are addressing low-value care without actually being forced to make any substantive changes.”
• “My experience mirrors the findings of a 2015 study that used surveys, interviews, and focus groups to assess how patients understood low-value care. The study found ‘quite powerfully” that patients favored “replacing excessive tests with time for clinicians to talk, listen and personalize'”
• “If Choosing Wisely is to continue, the specialty societies that have participated in it should celebrate its 10th anniversary by coming together to rethink and reinvent it.”

My take: While there are many factors that make it hard to eliminate low-value care, much is related to Upton Sinclair’s maxim: “It is difficult to get a man to understand something when his salary depends on his not understanding it.”

Related blog posts:

• Do you know about the “Choosing Wisely Campaign?”
• Healthcare: “Where the Frauds Are Legal”
• Trying to make Cents out of Value Care | gutsandgrowth
• The Costs of Unnecessary Care –What’s Wrong with “I want everything ruled out?”
• Why Are So Many “Low Value” Endoscopies Performed?
• What Does Richard Thaler’s Work Mean for Medicine?