Pharmacologic treatment of GERD: Where we are now, and where are we going?

Abstract

The introduction of acid inhibition in clinical practice has revolutionized the management of acid-related diseases, leading to the virtual abolition of elective surgery for ulcer disease and relegating antireflux surgery to patients with gastroesophageal reflux disease (GERD) not adequately managed by medical therapy. Proton pump inhibitors (PPIs) are the antisecretory drugs of choice for the treatment of reflux disease. However, these drugs still leave some unmet clinical needs in GERD. PPI-refractoriness is common, and persistent symptoms are observed in up to 40-55% of daily PPI users. Potassium-competitive acid blockers (P-CABs) clearly overcome many of the drawbacks and limitations of PPIs, achieving rapid, potent, and prolonged acid suppression, offering the opportunity to address many of the unmet needs. In recent years, it has been increasingly recognized that impaired mucosal integrity is involved in the pathogenesis of GERD. As a consequence, esophageal mucosal protection has emerged as a new, promising therapeutic avenue. When P-CABS are used as add-on medications to standard treatment, a growing body of evidence suggests a significant additional benefit, especially in the relief of symptoms not responding to PPI therapy. On the contrary, reflux inhibitors are considered a promise unfulfilled, and prokinetic agents should only be used on a case-by-case basis.

Pharmacological Management of Gastro-Esophageal Reflux Disease: An Update of the State-of-the-Art

“…In recent years, another mechanism, such as the reduction of defensive properties of esophageal mucosa has been advocated in the pathogenesis of GERD. 16 There are many studies showing that the mucosal resistance of the esophagus is impaired in most patients with GERD, particularly in those with non-erosive reflux disease (NERD), who do not present mucosal lesions at endoscopy. 16,17 Indeed, the presence of dilated intercellular spaces (DIS) is common in patients with true NERD and reflux hypersensitivity (RH) because of the presence of an impaired mucosal barrier.…”

“…16 There are many studies showing that the mucosal resistance of the esophagus is impaired in most patients with GERD, particularly in those with non-erosive reflux disease (NERD), who do not present mucosal lesions at endoscopy. 16,17 Indeed, the presence of dilated intercellular spaces (DIS) is common in patients with true NERD and reflux hypersensitivity (RH) because of the presence of an impaired mucosal barrier. 18 In patients with NERD it has been shown that microscopic esophagitis, including DIS, is significantly lower in controls (15%) and in patients with functional heartburn (FH) (13%) than in patients with RH (65%) and in those with excess of acid (77%).…”

“…91 Both compounds exhibit multiple functions, such as anti-inflammatory effect, wound repair, tissue regeneration and modulation of cytokines expression. 16 A prospective, randomized clinical trial performed in Italy in NERD patients compared Esoxx TM combined with a standard PPI dose to PPI plus placebo. 92 The combined therapy protracted for 14 days was significantly better than the latter one in relieving symptoms and improving the quality of life of recruited patients.…”

Gastroesophageal Reflux Disease: A Practical Approach

“…PPIs have been widely used for decades, but the number of recent publications questioning their safety has increased dramatically, causing considerable patient anxiety. Evidence has shown that they are risk-free drugs with relatively rare adverse effects and very low mortality (61,62) . There are certainly cases where there is a risk of vascular complications, regardless of the use of PPIs, such as in elderly patients with diabetes, hypertension, and history of strokes, who often require aspirin for prophylaxis of cardio-cerebrovascular events (63) .…”

Pharmacologic treatment of GERD in adolescents: Is esophageal mucosal protection an option?

“…They include inhibition of peptic digestion, mucosal protection through mucus and bicarbonate production, and stimulation of tissue growth and repair. 46 In the past, sucralfate has been extensively used in adults with GERD, 47 but with advent of PPIs, it was relegated to other gastrointestinal (GI) conditions. The available data are inadequate to determine the safety or efficacy of sucralfate in the treatment of GERD in children, particularly the risk of aluminum toxicity with long-term use.…”