Learning > The art of GORD treatment

Evolution of therapy for reflux disease: where are we? Where are we going? JP Galmiche CHU, Nantes, France

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Gastro-oesophageal reflux disease (GORD) is a frequent disorder that encompasses a wide spectrum of digestive and extradigestive manifestations. Most patients are seen in a primary care setting and do not have mucosal breaks at endoscopy. However, endoscopy-negative GORD (or non erosive disease) is not a mild disease because symptoms do impact quality of life. Therefore, the goals of therapy include not only the healing of lesions, but also the relief of symptoms and prevention of relapses and complications. From a pathophysiological point of view, GORD is a multifactorial disease but acid-peptic injury plays a central role in the pathogenesis of symptoms and lesions, as shown by the dramatic efficacy of proton pump inhibitors (PPIs). These drugs are not only more efficacious than H2-blockers, but they heal oesophagitis and relieve symptoms faster than H2-antagonists. However, the first developed PPIs have important shortcomings e.g. slow speed of onset of acid inhibition, difficulty to reach complete acid suppression, variable in vivo bioavailability, possible interference with cytochrome P450. Even twice daily doses of PPIs do not suppress nocturnal gastric acidity and this nocturnal acid breakthrough may be therapeutically relevant to the treatment of severe complicated GORD, e.g. Barrett's oesophagus. There are different manners to improve acid inhibition with a PPI. Rabeprazole, for example, has a higher pKa and is more rapidly activated into its active form. Another option is to develop selective enantiomers with a more potent inhibitory effect, e.g. esomeprazole versus omeprazole. With respect to the long-term management of the disease there are now different strategies including continuous maintenance with different doses of PPIs (or H2-antagonists if step-down is possible), intermittent therapy (if relapses are infrequent) or on-demand therapy with a PPI in endoscopy-negative GORD. The role of Helicobacter pylori (aggravating factor, innocent bystander or protective agent?) and subsequently, the benefit/risk ratio of its eradication in GORD are still a matter of debate. Independently of the effect of Helicobacter pylori, it is also important to consider the risk of development of corpus mucosal atrophy when long-term acid suppression is maintained in infected patients. Because Helicobacter pylori is a carcinogenic agent, it is the opinion of the author that eradication should be recommended before embarking in long-term maintenance PPI therapy, especially in a patient with an antecedent family history of gastric carcinoma. Although laparoscopic surgery is effective in well-selected patients, there is no clear evidence from the literature that it is superior to modern medical therapy in terms of cost/effectiveness or prevention of complications such as oesophageal adenocarcinoma. An alternative option to anti-reflux surgery may be one or several of the various endoscopic modalities currently tested worldwide in patients with PPI&endash;dependent GORD. However, so far, the literature does not support a clear benefit of these endoscopic treatments compared to PPIs in terms of control of oesophageal acid exposure. The results of well-designed controlled studies, performed in reference centers, are therefore eagerly awaited before these endoscopic procedures should be recommended in routine practice.   View the Keyslides: Text and slides Broadband video

 

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