Twice-Daily Dosage of Rabeprazole (RPZ) found to be more effective than a Single-Daily Dosage for Severe Reflux-Esophagus Disease

Reference: Kinoshita, Y. and M. Hongo, Efficacy of Twice-Daily Rabeprazole for Reflux Esophagitis Patients Refractory to Standard Once-Daily Administration of PPI: The Japan-Based TWICE Study. Am J Gastroenterol, 2012.

A study out of Japan on the effect of a twice-daily dosage vs. a once-daily dosage for patients with severe Reflux Esophagitis disease who do not initially respond to a proton pump.  

Brief Summary:  About 10 percent of Reflux Esphagitis (RE) patients do not initially respond to proton pump inhibitors (PPIs) - especially common in those with severe RE.  The main objective of this study was to determine whether increasing the effective dosage of a type of PPI called rabeprazole (RPZ) would lead to significant healing.  Specifically, it was desired to see if a 10 or 20 m.g. b.i.d. (twice-daily) regime dosage is more effective than a 20 m.g. q.d. (once-daily) regime dosage of RZ.  About 330 patients were randomly assigned to three different groups consisting of a 10 m.g. b.i.d., 20 m.g. b.i.d., or 20 m.g. q.d. regime dosage.   The primary comparison end-point between the three groups was the rate of endoscopically confirmed healing after 8 weeks, and a second end-point comparison was the weekly heartburn resolution after 4 weeks.    

Results: In general, a regime of 10 or 20 m.g. twice-daily dosage of RPZ was found to be more effective than a 20 m.g. single-daily dosage among patients who did not respond to initial treatments of PPI. Specifically, patients with Los Angeles grade A or B RE were found to respond optimally to a regime dosage of 10 m.g. twice-daily RPZ whereas patients with Los Angeles grade C or D RE were found to respond optimally to a regimen dosage of 20 m.g. twice-daily RPZ.  The heartburn resolution also decreased for the two twice-daily regimens.  The Los Angeles classification system is typically used to classify Esophagitis patients into four different groups based on severity.  Group A is the least severe and Group D is the most severe.   

Implications for Practice: If a patient does not respond initially to the standard proton pump inhibitor (PPI) regimen, then the patient should be prescribed either a 10 or 20 m.g. b.i.d. regimen of Rabeprazole (RPZ). If it is known that the patient has type A or B, prescribe 10 m.g. twice-daily of RPZ; if it’s known that the patient has type C or D, prescribe 20 m.g. twice-daily of RPZ.

Discussion: More studies like this need to be done in order to elucidate the optimal dosage for a given condition.  It was interesting that Los Angeles group A and B patients were found to have a different optimal dosage than group C or D patients.

Brief Commentary on Statistics and Study Design: The authors used the Cochran-Armitrage test which can be used for this purpose. However, since the outcome variable was continuous, it would have been more simple and easy just to use simple general linear regression (GLR) or an ANOVA model, and this is what really should have been used. The advantage of using a GLR is that it is fairly simple to control for any other potential confounding variables.  Indeed, there are several other demographic variables that could have been included.  The ANOVA model could have then been used to compare the means from the three different groups and are setup specifically for experiments like this.  In statistics (as in most anything in life), the simplest solution is usually the best.