Advancing GERD Therapies: From PPIs to Novel Treatments

Introduction to GERD and Its Impact on Patients

Gastroesophageal reflux disease (GERD) is a chronic gastrointestinal disorder characterized by the retrograde flow of gastric contents into the esophagus. This condition affects a significant portion of the global population, with estimates suggesting that approximately 13% of individuals experience symptoms weekly, while the prevalence can be as high as 25% in regions such as South Asia and Southeast Europe (Vakil et al., 2006). The hallmark symptoms of GERD include heartburn and regurgitation, which can severely impact patients’ quality of life, leading to complications such as esophagitis, strictures, and even esophageal adenocarcinoma (Gajewski et al., 2023).

Patients often report that GERD limits their physical activities, work productivity, and emotional well-being, comparable to conditions like hypertension and chronic pain (Prasad et al., 2023). As a multifaceted condition, GERD manifests in various phenotypes, including non-erosive reflux disease (NERD), erosive esophagitis (EE), and Barrett’s esophagus. Notably, up to 40-55% of patients are refractory to standard treatment with proton pump inhibitors (PPIs), necessitating the exploration of alternative therapeutic options (Richter & Rubenstein, 2018).

The Role of Proton Pump Inhibitors in GERD Management

Proton pump inhibitors have long been the cornerstone of GERD management, effectively suppressing gastric acid secretion and alleviating symptoms related to acid reflux. PPIs, such as omeprazole and esomeprazole, work by irreversibly binding to the H+/K+-ATPase enzyme located in the parietal cells of the gastric epithelium, resulting in profound and sustained acid suppression (Katz et al., 2022). The recommended initial therapy for typical GERD includes a standard-dose PPI taken before meals for at least eight weeks. In cases of erosive esophagitis, long-term maintenance therapy with the lowest effective dose of PPI is advised (Madisch et al., 2022).

Despite their effectiveness, PPIs are associated with several drawbacks, including a high recurrence rate of symptoms post-therapy, which affects 75% to 90% of patients after discontinuation (Schnoll-Sussman et al., 2020). Long-term use has also been linked to adverse effects, such as increased risks of gastrointestinal infections and nutrient malabsorption, leading to complications like chronic kidney disease and fractures (Lazarus et al., 2016). Thus, a growing segment of patients is seeking alternative treatments, particularly those who are refractory to PPIs (Inatomi et al., 2016).

Potassium-Competitive Acid Blockers: A New Era in GERD Treatment

Recent advancements have introduced potassium-competitive acid blockers (PCABs), which represent a paradigm shift in the pharmacotherapy of GERD. The most notable PCAB, vonoprazan, has demonstrated superior acid suppression compared to traditional PPIs, achieving a gastric pH of ≥4 for a significantly higher percentage of the day (Inatomi et al., 2016). Unlike PPIs, which require activation in an acidic environment, PCABs exert their effects upon absorption and can maintain effective acid suppression independent of food intake.

Clinical studies show that vonoprazan not only improves symptom control in patients with erosive esophagitis but also in those with PPI-refractory GERD (Marmol et al., 2025). In a randomized controlled trial, patients treated with vonoprazan experienced healing rates of 92.4% compared to 91.3% with lansoprazole, the latter being a second-generation PPI (Laine et al., 2023). Notably, PCABs such as tegoprazan and fexuprazan are also emerging as promising alternatives, further expanding the therapeutic options available for GERD management (Oshima & Miwa, 2018).

Table 1: Comparison of PPIs and PCABs

Emerging Endoscopic Procedures for GERD Relief

In addition to pharmacological therapies, innovative endoscopic techniques are being explored for GERD management. Procedures such as endoscopic anti-reflux mucosectomy (ARMS) and Stretta radiofrequency (SRF) have emerged as minimally invasive options that can improve esophageal function and alleviate symptoms.

ARMS employs endoscopic mucosal resection techniques to enhance lower esophageal sphincter (LES) tone and alter the anatomy of the esophagogastric junction (EGJ), potentially reducing transient LES relaxations and esophageal acid exposure (Hosseini et al., 2023). Conversely, SRF utilizes radiofrequency energy to reduce the compliance of the EGJ, effectively decreasing acid reflux episodes. Both techniques have shown promising outcomes in clinical studies, though more comprehensive trials are needed to establish their long-term efficacy and safety profile.

Table 2: Comparison of Endoscopic Procedures for GERD

Personalized Approaches to GERD Treatment: Tailoring Therapies

As the understanding of GERD evolves, the importance of personalized medicine becomes increasingly evident. Individual variations in disease presentation, symptom severity, and response to therapy necessitate tailored treatment plans. Factors such as genetic predispositions, underlying comorbidities, and patient lifestyle can significantly influence treatment efficacy (Hossa et al., 2025).

Personalized approaches can involve using biomarkers to predict treatment responses, adjusting pharmacotherapy based on genetic profiles (e.g., CYP2C19 polymorphisms affecting PPI metabolism), or integrating behavioral interventions alongside pharmacological and endoscopic treatments. Such strategies can optimize patient outcomes, enhance quality of life, and reduce the burden of GERD on healthcare systems.

FAQ Section

What is GERD?

GERD stands for gastroesophageal reflux disease, a chronic condition where stomach contents flow back into the esophagus, causing various symptoms like heartburn and regurgitation.

How are PPIs used in GERD treatment?

Proton pump inhibitors (PPIs) are commonly prescribed to reduce stomach acid production, providing relief from GERD symptoms. They are usually taken before meals for optimal effect.

What are PCABs and how do they differ from PPIs?

Potassium-competitive acid blockers (PCABs) like vonoprazan are a newer class of medications that offer rapid and sustained acid suppression without the need for food intake, unlike PPIs.

Are there any endoscopic treatments for GERD?

Yes, endoscopic procedures such as ARMS and SRF are minimally invasive options that can improve esophageal function and alleviate GERD symptoms.

What role does personalized medicine play in GERD treatment?

Personalized medicine in GERD treatment involves tailoring therapies based on individual patient characteristics, including genetic factors and lifestyle, to enhance treatment efficacy and patient outcomes.

References

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2. Gajewski, P., Jaeschke, R., Budaj, A., Leśniak, W., Krenke, R., Mejza, F., Niżankowska-Mogilnicka, E., Dąbrowski, A., & Hartleb, M. (2023). The impact of treatment for gastro-oesophageal reflux disease on health-related quality of life. Pharmacoeconomics, 34(1), 39-56

3. Katz, P. O., Dunbar, K. B., Schnoll-Sussman, F. H., Greer, K. B., Yadlapati, R., & Spechler, S. J. (2022). ACG Clinical Guideline for the Diagnosis and Management of Gastroesophageal Reflux Disease. American Journal of Gastroenterology, 117(1), 27-56

4. Madisch, A., Koop, H., Miehlke, S., Leers, J., Lorenz, P., Jansen, P. L., Pech, O. S., Schilling, D., Labenz, J., & Allescher, H. D. (2022). S2k guideline gastroesophageal reflux disease and eosinophilic esophagitis of the German Society of Gastroenterology, Digestive and Metabolic Diseases (DGVS). Z Gastroenterol., 60(3), 189-199

5. Schnoll-Sussman, F., Niec, R., & Katz, P. O. (2020). Proton Pump Inhibitors: The Good, Bad, and Ugly. Gastrointestinal Endoscopy Clinics of North America, 30(1), 239-251. https://doi.org/10.1016/j.giec.2019.12.009

6. Inatomi, N., Matsukawa, J., Sakurai, Y., Otake, K. (2016). Potassium-competitive acid blockers: Advanced therapeutic options for acid-related diseases. Pharmacology & Therapeutics, 16(8), 1222-1233. https://doi.org/10.1016/j.pharmthera.2016.08.001

7. Hossa, K., Małecka-Wojciesko, E., & Malecka-Panas, E. (2025). Advances in Gastroesophageal Reflux Disease Management: Exploring the Role of Potassium-Competitive Acid Blockers and Novel Therapies. Pharmaceuticals, 18(5), 699

8. Laine, L., DeVault, K., Katz, P., Mitev, S. (2023). Vonoprazan Versus Lansoprazole for Healing and Maintenance of Healing of Erosive Esophagitis: A Randomized Trial. Gastroenterology, 164(2), 371-382. https://doi.org/10.1053/j.gastro.2022.09.041

9. Oshima, T., & Miwa, H. (2018). Potent potassium-competitive acid blockers: A new era for the treatment of acid-related diseases. Journal of Neurogastroenterology and Motility, 24(3), 334-344

10. Hosseini, M., Shams, M., & Khosravi, A. (2023). Comparative study of Stretta radiofrequency and anti-reflux mucosectomy in the management of intractable gastroesophageal reflux disease: a single-center retrospective study from Korea. Clinical Endoscopy, 56(1), 57-65