Abstract & Commentary
Synopsis: In patients with symptomatic nonerosive reflux disease, intermittent on-demand therapy with the PPI rabeprazole provided good symptom control with tablets taken on average approximately 1 day out of 4.
Source: Bytzer P, et al. Alimentary Pharmacology & Therapeutics. 2004;20:181-188.
Gastroesophageal reflux disease (GERD) is extremely common, but at least 50-70% of patients with GERD symptoms have normal esophageal mucosa on endoscopy. Despite physicians’ assumptions to the contrary, compliance studies strongly suggest that patients with reflux symptoms generally only take their medications while actually experiencing reflux-related symptoms. This nonerosive reflux disease (NERD) study was undertaken to assess the on-demand efficacy of rabeprazole (a PPI noted for relatively rapid onset of profound acid suppression). Five hundred thirty-five NERD patients with = 3 d/wk of baseline moderate-to-severe heartburn were enrolled (numbers based on power calculations).
All patients took rabeprazole 10 mg daily for 4 weeks. Thereafter, patients were randomized to either rabeprazole 10 mg or placebo (2:1 allocation), taken one tablet daily at heartburn onset and continued daily before breakfast until 24 hours without heartburn had transpired. Maalox was available for breakthrough symptoms. Twenty percent of placebo recipients withdrew from the study vs 6% of rabeprazole recipients. Symptom relief occurred significantly earlier with rabeprazole than with placebo. Rabeprazole was taken on 26% of possible days. Rabeprazole and placebo were both well tolerated. Bytzer and associates speculate that on demand therapy may have an important role in management of NERD and that such treatment would provide substantial cost savings vs continuous PPI therapy as has been traditionally prescribed.
Comment by Malcolm Robinson MD, FACP, FACG
This paper joins other similar studies of several other PPIs in the management of NERD. There seems to be little doubt that on-demand treatment could be clinically acceptable and economically advantageous in this setting. Although these studies have not addressed the absolute long-term safety of intermittent NERD therapy, existing information suggests that there should be no major difficulties with adoption of such regimens. That is, it seems unlikely that intermittently treated NERD patients would nonetheless develop significant mucosal injury, Barrett’s esophagus, or esophageal adenocarcinoma.
Ideally, of course, some prospective long-term investigations should be undertaken to verify the correctness of this hypothesis. The real question surrounds the possible dangers of using such intermittent therapy in uninvestigated GERD patients, some of whom might have significant esophageal mucosal abnormalities. Although no scientific data exist to completely answer this conundrum, it seems likely (at least to Bytzer et al) that intermittent PPI therapy might be quite satisfactory for GERD patients with lesser grades of esophageal damage (eg, tiny erosions at the squamocolumnar junction). It seems quite unlikely that mild esophagitis would progress in previously symptomatic patients whose symptoms are adequately controlled with intermittent therapy. However, this mild erosive GERD subgroup certainly should be prospectively studied before on- demand therapy is promoted in GERD patients who have not been evaluated by endoscopy. In this era of rapidly rising medical costs, the benefits of on demand PPI therapy certainly warrant careful consideration.
Dr. Robinson, Medical Director, Oklahoma Foundation for Digestive Research; Clinical Professor of Medicine, University of Oklahoma College of Medicine Oklahoma City, OK, is Associate Editor of Internal Medicine Alert.