![24 hours gastric pH4 HTR (Study V-E: Vonoprazan 20mg and Esomeprazole 20mg administered)
Vonoprazan 20 mg group (n=10)
Esomeprazole 20 mg group (n=10)
100
0
day 1 of administration day 7 of administration
80
60
40
20 23.9
61.2
71.4
85.8
pH4HTR
Average value ±standard deviation
pH4 HTR: pH≧4 Holding Time Ratio (Holding time ratio is greater than pH 4)
Difference between both
drugs (%) [95% CI]
47.5 [35.5, 59.4] Difference between both
drugs (%) [95% CI]
24.6 [16.2, 33.1]
Sakurai Y, et al: Aliment Pharmacol Ther. 2015; 42 (6): 719-730
(%)
Target and method: In a randomized, open-label 2-period crossover study of 20 adult Japanese males with CYP2C19 genotype EM
(including hetero EM, homo EM), once daily dose of Vonoprazan 20mg and Esomeprazole 20mg (Study V-E, n=10), Vonoprazan
20mg and Rabeprazole 10mg (Study V-R, n=10) was administered for 7 days.](https://image.slidesharecdn.com/gerdaug18v2-180809133415/85/GERD-Current-Paradigms-36-320.jpg)
![Difference between both
drugs (%) [95% CI]
58.2 [43.6, 72.9]
Difference between both
drugs (%) [95% CI]
28.8 [17.2, 40.4]
24 hours gastric pH4 HTR (Study V-R: Vonoprazan 20mg and Rabeprazole 10mg administered)
Vonoprazan 20 mg group (n=7)
Rabeprazole 10 mg group (n=7)
Average value ±standard deviation
pH4 HTR: pH≧4 Holding Time Ratio (Holding time ratio is greater than pH 4)
100
(%)
0
day 1 of administration day 7 of administration
80
60
40
20
pH4HTR
26.3
65.1
93.8
84.2
Target and method: In a randomized, open-label 2-period crossover study of 20 adult Japanese males with CYP2C19 genotype EM
(including hetero EM, homo EM), once daily dose of Vonoprazan 20mg and Esomeprazole 20mg (Study V-E, n=10), Vonoprazan
20mg and Rabeprazole 10mg (Study V-R, n=10) was administered for 7 days.
Sakurai Y, et al: Aliment Pharmacol Ther. 2015; 42 (6): 719-730. More figures](https://image.slidesharecdn.com/gerdaug18v2-180809133415/85/GERD-Current-Paradigms-37-320.jpg)
Uploaded byJarrod Lee
GERD: Current Paradigms
The document discusses the pathophysiology, diagnosis, and treatment of gastroesophageal reflux disease (GERD), focusing on its prevalence among pregnant women and the spectrum of the condition. Key points include the evaluation of heartburn symptoms for diagnosis, the limited role of endoscopy, and various treatment options, including lifestyle changes and medications like proton pump inhibitors. It also highlights emerging treatments and the evolution of GERD paradigms over the last two decades.
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GERD: Current Paradigms
- 1. GERD: Current Paradigms DrJarrod Lee Gastroenterologist & Advanced Endoscopist Peer to Peer Workshop Rosso Bianco 2 Aug 2018
- 2. Scope • Pathophysiology • Clinicalspectrum • Natural history • Diagnosis • Medical treatment
- 3. What Causes GERD? •Transient relaxation of lower esophageal sphincter (LES) exposes esophagus to stomach acid and contents • Factors that increase exposure • Increased intra-abdominal pressure: pregnancy, obesity • Descreased esophageal or gastric motility • Hiatal hernia • Increased esohageal sensitivity predisposes to more severe symptoms or tissue damage • NOT due to increased acid production
- 4.
- 5. • Increased prevalencein pregnancy: 30-50% of pregnant women complain of heartburn • Predictors of heartburn: gestational age, parity, presence of heartburn before pregnancy • Diagnosis and treatment should be based on symptoms • Usually resolves after delivery • Limited treatment data: small trials, no RCTs For Healthcare Professionals Only
- 6. What causes Heartburnin Pregnancy? Hormonal Changes • Increased of circulating progesterone relaxes the LES, allowing food and acid to flow back up into the esophagus Increase in intra-abdominal pressure • Growing fetus pushes up on the stomach and increase pressure on the abdominal
- 7.
- 8. Natural History: TraditionalParadigm • Progression along spectrum over time • NERD is a mild form of GERD • Focus on Erosive Esophagitis • Most well designed GERD studies focus on mucosal healing and symptom improvement in Erosive Esophagitis NERD Erosive Esophagitis Barrett’s Esophagus
- 9. NERD: Where isthe Evidence? • Most community based patients have NERD • Few progress to Erosive Esophagitis • 10-15% over 5-20 years • Only mild Erosive Esophagitis (Grade A) • No Barrett’s Esophagus or Cancer • Lower symptom response to PPIs • Increased number of treatment failures • Relapse back to NERD after treatment
- 10. Epidemiology: East vsWest • GERD Incidence: • West: 10-20% • Asia: 5% • Singapore: 10% • NERD percentage • West: 50-70% • Asia: 60-90% 10 NERD EE
- 12.
- 13. How is GERDdiagnosed? • No gold standard!! • Presumptive diagnosis can be made with typical symptoms: • Heartburn, acid regurgitation • Frequency: at least weekly • If presumptive diagnosis made, can proceed to an empirical trial of PPI • Good Sensitivity 75-85%: 4-8 weeks of PPI will control symptoms in 75-85% • Poor Specificity 25-65%: may be positive in other acid disorders; specificity with placebo 40% !!
- 14. What is the Roleof Endoscopy? I’m worried and concerned Symptoms bother me! My whole life is affected Heartburn disturbs my sleep I cannot eat or drink what I like I cannot bend over or exercise
- 15. Endoscopy in UncomplicatedGERD • Good specificity but poor sensitivity < 30% • Only 10% sensitivity in Asia • Problem with patients on treatment • NO ROLE FOR DIAGNOSIS!! • Used for: • Evaluate treatment failures and atypical symptoms • Evaluate alarm symptoms: dysphagia, LOW, persistent vomiting, bleeding, anemia • Screen for Barrett’s Esophagus if at risk: males > 50 yrs with chronic GERD
- 16.
- 17. Narrow Band Imaging Improvesvisualization of squamo-columnar junction
- 18. NBI in GERD EndoscopyFinding Conventional Endoscopy Advanced Imaging Micro-erosions 0% 52.8% Increased vascularity at junction 0% 91.7%
- 19. NBI in NERD Usinga composite of: increased vascularity & absence of round pit pattern • Sensitivity 86.1% • Specificity 83.3% Advanced Imaging NERD Controls P Micro erosions 52.8% 23.3% < 0.001 Increase vascularity 91.7% 36.7% < 0.001 Round pit pattern 5.6% 70% < 0.001
- 20. • Increased number,dilatation, tortuosity of intrapapillary capillary loops (IPCLs) • Micro-erosions, increased vascularity • Absence of round pit pattern
- 21.
- 22. Lifestyle Measures • Eatsmaller meals • Avoid eating late at night (2-3 hours before sleep) • Elevation of head of the bed or sleep in left lateral position • Lose weight, stop smoking • Dietary modifications may improve symptoms or reduce complications, but evidence is very weak • Some foods may lower LES tone (carminatives) • Other foods may irritate inflamed esophageal mucosa (citrus) • Patients may report improvement when avoiding particular substances
- 23.
- 24. The Acid Pocketand Hiatal Hernia
- 25. Alginate (Barrier) Antacids • Alginatesare natural polymers extracted from brown algae (kelp) • In acidic environment, form a viscous gel-raft that floats; bicarbonate neutralizes acid • Alginate raft refluxes into esophagus before gastric contents • Provides a physical barrier to prevent reflux of gastric contents • Coats the esophagus with rafts, which acts as protective layer
- 26. Alginate Antacids in Pregnancy •Recommended 1st line drug • Safe and effective: 90% response in pregnant women • Rapid relief: 90% within 20 minutes • Lasts up to 4H • Best used ‘on demand’ 0 20 40 60 80 100 120 0 <10 10-<20 20-<30 30-<60 >60 Time (min) Cumulativepercentageof patientswithonsetofsymptom relief B. Patient Assessment 0 10 20 30 40 50 60 Very Good Good Acceptable Poor V Poor Efficacy Rating Patientsreportingefficacy ofproduct(%)
- 27.
- 28. H2 Receptor Antagonists • Competitivelyhistamine binding on gastric parietal cells • Helps heal erosive esophagitis and improve symptoms • Use limited by tachyphylaxis; best used ‘on demand’ • Safe in pregnancy
- 29. Proton Pump Inhibitors (PPIs) • First-lineagents for patients with erosive disease or with typical symptoms • Irreversibly inhibit parietal cell proton pump • More potent acid suppressors than H2RAs, no tachyphylaxis • Safe in pregnancy
- 30. PPI therapy inGERD • NOT a definite solution – Symptoms will recur once PPI stopped – Reduces acidity but not frequency or volume of reflux • Efficacy in Erosive Esophagitis – Mucosal healing: 85-95% – Symptomatic response: 75-85% • Reasons for PPI failure – Compliance – Concomitant functional disorder, e.g. IBS, FD – Wrong diagnosis – NERD
- 31.
- 32. Ambulatory 24H pHImpedance Monitoring • ‘Gold’ standard for GERD diagnosis • Documents ALL reflux; improves GERD diagnosis in up to 90% • Correlates symptoms with reflux event • Can differentiate NERD subtypes
- 33.
- 34. Lyon Consensus forGERD Diagnosis 2018
- 35. Potassium Competitive Acid Blocker(PCAB) • New acid suppressant drug • Fast and profound acid suppression • Reversibly inhibits parietal cell proton pump • Dosing independent of meal times • Compared to PPI: longer half life in blood, more stable in acidic environment, and can inhibit new proton pumps that are synthesized
- 36. 24 hours gastricpH4 HTR (Study V-E: Vonoprazan 20mg and Esomeprazole 20mg administered) Vonoprazan 20 mg group (n=10) Esomeprazole 20 mg group (n=10) 100 0 day 1 of administration day 7 of administration 80 60 40 20 23.9 61.2 71.4 85.8 pH4HTR Average value ±standard deviation pH4 HTR: pH≧4 Holding Time Ratio (Holding time ratio is greater than pH 4) Difference between both drugs (%) [95% CI] 47.5 [35.5, 59.4] Difference between both drugs (%) [95% CI] 24.6 [16.2, 33.1] Sakurai Y, et al: Aliment Pharmacol Ther. 2015; 42 (6): 719-730 (%) Target and method: In a randomized, open-label 2-period crossover study of 20 adult Japanese males with CYP2C19 genotype EM (including hetero EM, homo EM), once daily dose of Vonoprazan 20mg and Esomeprazole 20mg (Study V-E, n=10), Vonoprazan 20mg and Rabeprazole 10mg (Study V-R, n=10) was administered for 7 days.
- 37. Difference between both drugs(%) [95% CI] 58.2 [43.6, 72.9] Difference between both drugs (%) [95% CI] 28.8 [17.2, 40.4] 24 hours gastric pH4 HTR (Study V-R: Vonoprazan 20mg and Rabeprazole 10mg administered) Vonoprazan 20 mg group (n=7) Rabeprazole 10 mg group (n=7) Average value ±standard deviation pH4 HTR: pH≧4 Holding Time Ratio (Holding time ratio is greater than pH 4) 100 (%) 0 day 1 of administration day 7 of administration 80 60 40 20 pH4HTR 26.3 65.1 93.8 84.2 Target and method: In a randomized, open-label 2-period crossover study of 20 adult Japanese males with CYP2C19 genotype EM (including hetero EM, homo EM), once daily dose of Vonoprazan 20mg and Esomeprazole 20mg (Study V-E, n=10), Vonoprazan 20mg and Rabeprazole 10mg (Study V-R, n=10) was administered for 7 days. Sakurai Y, et al: Aliment Pharmacol Ther. 2015; 42 (6): 719-730. More figures
- 39. Take Home Message •GERD paradigms have evolved considerably in the past 20 years. • Treatment algorithm has become more sophisticated. • Refer PPI refractory GERD patients to a Gastroenterology service with motility capability. 39