What are the emerging treatments for Gastroesophageal Reflux Disease (GERD)?

Emerging Treatments for GERD

Novel Pharmacological Agents

Potassium-competitive acid blockers (P-CABs), such as vonoprazan, represent the most significant emerging pharmacological treatment for GERD, though they should generally not be used as first-line therapy for uninvestigated heartburn or nonerosive GERD due to higher costs, less availability, and less robust long-term safety data compared to PPIs. 1

• P-CABs offer faster onset of action and more sustained acid suppression compared to traditional PPIs, particularly in patients with refractory symptoms 1
• These agents may be particularly useful in patients who have failed standard PPI therapy, though guidelines currently recommend optimizing PPI dosing (twice-daily) before switching to alternative agents 2, 3

Emerging Surgical and Endoscopic Interventions

Minimally invasive endoscopic and surgical techniques are increasingly replacing traditional fundoplication, offering comparable efficacy with reduced morbidity. 2, 4

Magnetic Sphincter Augmentation

• This device-based intervention is often combined with crural repair in the setting of hiatal hernia and represents a less invasive alternative to traditional fundoplication 2
• It provides mechanical augmentation of the lower esophageal sphincter without altering gastric anatomy 2

Transoral Incisionless Fundoplication (TIF)

• This endoscopic option is appropriate for carefully selected patients with GERD in the absence of a hiatal hernia 2
• It offers the advantage of no external incisions and faster recovery compared to laparoscopic approaches 2

Tailored Fundoplication Approaches

• Partial fundoplication is increasingly preferred in patients with esophageal hypomotility to reduce postoperative dysphagia risk 2
• Laparoscopic fundoplication remains effective, with the LOTUS trial showing 85% remission at 5 years, though this was slightly lower than medical therapy (92%) 5, 3

Bariatric Surgery as Anti-Reflux Intervention

• Roux-en-Y gastric bypass is effective as a primary anti-reflux intervention in obese patients with GERD, addressing both obesity and reflux simultaneously 2

Adjunctive Pharmacological Strategies

For patients with partial response to PPIs, adding alginates or H2-receptor antagonists represents an emerging strategy, though baclofen shows promise despite tolerability concerns. 5, 2

• Sodium alginate added to PPI therapy resulted in significantly greater rates of complete heartburn resolution in patients with nonerosive reflux disease (NERD) 5
• Alginate-antacid raft formulations localize the postprandial acid pocket and displace it below the diaphragm, reducing post-reflux episodes 5
• Baclofen, a GABA agonist, decreases 24-hour pH scores and acid exposure time, useful as add-on therapy to PPI, but limited by side effects including somnolence, dizziness, weakness, and trembling 5

Prokinetic Agents

• Available prokinetics in Asia include mosapride, itopride, and domperidone, though their overall effect is modest 5
• A systematic review comparing mosapride plus PPI with PPI monotherapy did not show significant benefit 5
• Adding prokinetic therapy may be considered for patients with persistent symptoms despite optimized PPI therapy, particularly those with extraesophageal symptoms 1, 2

Behavioral and Neuromodulatory Interventions

Cognitive behavioral therapy, gut-directed hypnotherapy, and neuromodulators represent emerging non-pharmacological options for patients with overlapping functional symptoms. 2

• These interventions are particularly beneficial for patients with functional esophageal disorders who may benefit from gradual PPI tapering 2
• Neuromodulation addresses the hypersensitivity component that may persist despite adequate acid suppression 2

Important Caveats and Clinical Considerations

• Metoclopramide should be avoided as monotherapy or adjunctive therapy for GERD due to its unfavorable risk-benefit profile, including risk of tardive dyskinesia 1, 3
• For extraesophageal GERD symptoms (chronic cough, laryngitis, asthma), more intensive therapy including twice-daily PPI dosing for 8-12 weeks is required, though response rates are lower than for typical GERD symptoms 1, 2
• Before considering emerging surgical or endoscopic interventions, patients should fail a minimum of 3 months of intensive medical therapy with objective documentation of persistent GERD 1, 3
• The safety profile of long-term PPI therapy should be emphasized to patients, as concerns about potential risks often lead to poor adherence, though for confirmed erosive esophagitis or Barrett's esophagus, benefits outweigh risks 1, 3

Weight Loss as Emerging Priority

• Weight loss in overweight or obese patients has the strongest evidence of efficacy among all interventions and should be recommended to all such patients 1, 2, 3
• The HUNT study demonstrated a dose-dependent association between weight loss and reduction of GERD symptoms, with >3.5 unit decrease in BMI showing an odds ratio of 1.98 for loss of reflux symptoms 5