Editorial: Healing Erosive Esophagitis With a Proton Pump Inhibitor: The More the Merrier?

Abstract

Patients with erosive esophagitis (EE) account for 30 % of patients with gastroesophageal refl ux disease; only a minority of these patients fail to achieve healing on treatment with a proton pump inhibitor (PPI), once-daily, for 8 weeks. For those patients with EE who have failed to heal on a PPI, given once-daily, current practice is to double the PPI dose although there is little published evidence to support this. In this issue of the American Journal of Gastroenterology , authors from Japan have demonstrated that double-dose PPI produced higher healing rates when given as a split, twicedaily dose than as a once-daily dose for patients with EE who had failed initial therapy with rabeprazole 10 mg once-daily. Quadruple-dose PPI, given as a split dose, did not increase the healing rates but did produce better symptom control, albeit limited, compared with double-dose PPI, given twice-daily. Because subjects, initially, received a lower PPI dose than that generally indicated for EE (rabeprazole 20 mg daily), this study does not provide the eagerly awaited justifi cation for double-dose PPI therapy in patients with EE who have failed standard-dose PPI once-daily. However, it does demonstrate the clinical advantage of a split-dose regimen ( AM and PM ), compared with a once-daily regimen, when doubling the dose of a PPI for patients with residual EE after initial therapy. Am J Gastroenterol 2012; 107:531 -533; doi: 10.1038/ajg.2012 Th e introduction of the proton pump inhibitor (PPI) class of drugs has revolutionized treatment of erosive esophagitis (EE).Patients with EE receiving standard-dose PPI demonstrated 85 -96 % healing rates regardless of PPI brand and disease severity ( 1,2 ). However, despite the success of PPIs in healing EE, several areas of unmet need commonly result in PPI dose adjustments by practicing physicians. Patients with moderateto-severe EE (Los Angeles grades C and D) are less responsive to standard-dose PPI compared with patients with mild EE (Los Angeles grades A and B). One study demonstrated the following failure rates for subjects taking either omeprazole 20 mg once-daily or esomeprazole 40 mg once-daily: 9.6 and 6.6 % for Los Angeles grade A, 28.7 and 10.6 % for grade B, 29.6 and 12.8 % for grade C, and 36.2 and 20 % for grade D, respectively ( 3 ). In addition, the symptom resolution rate for those with EE receiving standard-dose PPI was 10 -15 % lower than the esophageal mucosal healing rate ( 4 ). Th e latter suggests that subjects with EE receiving PPI once-daily may continue to have GERD (gastroesophageal refl ux disease)-related symptoms despite complete esophageal healing. More disconcerting is that 10.2 -28.8 % of subjects with grades A and B and 15.9 -41.2 % with grades C and D experienced relapse within 6 months on maintenance with the same PPI dose (once-daily) that healed their EE initially ( 5 ). Consequently, it has become common practice to double the PPI dose in patients with EE who demonstrate partial or complete lack of response to standard-dose PPI. Howe...

Unmet Needs in the Treatment of Gastroesophageal Reflux Disease

“…13,18 Consequently, patients with EE receiving standard dose PPIs may still suffer from heartburn or regurgitation despite a complete resolution of the esophageal inflammation. 19 Moreover, even when continuing the initial healing dose as maintenance treatment for a period of 6 months, 15-23% of the patients with LA-A or LA-B, respectively, and 24-41% with LA-C or LA-D, respectively, relapsed while on treatment. 20 Higuchi et al 8 showed that (after a mean 1.1 years of PPI therapy) approximately 40% of patients did not achieve remission of esophageal inflammation and that healing of esophageal inflammation was significantly lower (42%) in patients with severe EE compared with patients having LA-A (71%).…”

A Meta-Analysis and Systematic Review of the Efficacy of Twice Daily PPIs versus Once Daily for Treatment of Gastroesophageal Reflux Disease

“…One trial [ 16 ] assessed the efficacy of standard dose of esomeprazole QD versus lansoprazole BID for GERD. In the United States and Europe, as well as many other countries around the world, rabeprazole 20 mg is considered as the standard dose for GERD therapy [ 20 ]. But in Japan, rabeprazole 10 mg is approved as a standard dose and 20 mg as a double dose [ 15 ].…”

The impact of intensifying acid suppression on sleep disturbance related to gastro‐oesophageal reflux disease in primary care

“…This effect could be due to bias but a systematic review has suggested that esomeprazole is more effective than standard doses of other PPIs used in the trial. It is possible that other PPIs used twice daily rather than once daily may have had a similar benefit to esomeprazole and this should be evaluated in future studies. This was a secondary outcome and therefore subjects with other reasons for sleep disturbance (e.g.…”