The present study compares the efficacy of the PPI rabeprazole to that of the H2RA ranitidine, as an on-demand option in the management of patients with NERD. The impact on QoL was also evaluated as a secondary outcome with both drug regimens.
Analysis of our data showed that rabeprazole is as effective as the routinely and commonly used ranitidine in controlling both the typical and atypical symptoms in patients with NERD. Evidence from several previous studies supports our findings regarding the efficacy of anti-secretory (H2
RA and PPI) therapy in patients with NERD[17-24
]. However, no head-to-head comparison between any H2RA and PPI had been carried out in the setting of on-demand therapy for NERD.
search identified a number of clinical trials[14,21-25
] that assessed the efficacy of various PPIs (rabeprazole, omeprazole, esomeprazole, lansoprazole) when given as on-demand in patients with NERD. Almost all of these studies were conducted over a period of time ranging from 3 mo to 6 mo and preceded by initial short periods (around 4-8 wk) of daily treatment with the designated PPI to achieve complete symptom resolution. A study by Lind et al[21
] randomized 424 patients with NERD to one of three groups: omeprazole 20 mg, omeprazole 10 mg, or placebo. After 6 mo of on-demand therapy, it was concluded that omeprazole was effective in the majority of NERD patients. In another placebo-controlled study, Talley et al[22
] assigned 342 patients to either esomeprazole 20 mg or placebo. On-demand therapy with esomeprazole 20 mg was found suitable for the long-term symptom management of NERD patients. In a separate placebo-controlled trial, Talley et al[23
] assessed the efficacy of on-demand therapy with esomeprazole 40 mg or 20 mg in patients with NERD and showed that both dosages were superior to placebo in controlling heartburn in those patients. Bytzer et al[24
] achieved favorable results in a 6-mo trial of on-demand rabeprazole 10 mg in patients with NERD. Five hundred and twenty-three patients with NERD were given 4 wk of rabeprazole 10 mg once daily. The 432 patients who had complete resolution of their symptoms were then randomized for the on-demand phase of the study to two groups: rabeprazole 10 mg and placebo. Symptom relief was significantly better in the rabeprazole group compared to the placebo group.
Rabeprazole was also investigated as on-demand treatment by Ponce et al[25
] in patients with NERD and low-grade esophagitis. Symptom control was maintained in over 85% of patients during six months of on-demand rabeprazole 20 mg therapy, following a 4-wk daily run-in period with rabeprazole 20 mg per day. During the study period, PPI consumption was found to be low and patient satisfaction with the treatment was high.
Rabeprazole appeared to be ideal for our study given its rapid onset of action and powerful acid suppression[14-16
]. Studies involving NERD patients have documented its superiority over placebo. In addition, on-demand use of rabeprazole for the management of NERD incurs the least cost in comparison with other PPIs[26
RAs have been widely used on-demand for patients with GERD. Clinical studies have demonstrated that, when given on-demand, they are superior to placebo in controlling heartburn in this group of patients[18,19,27
]. These findings may be extrapolated to NERD patients who constitute the majority of patients with GERD. H2
RAs are known to have a rapid onset, but a short duration of action. They suppress acid for approximately 4 to 8 h and produce incomplete inhibition of post-prandial gastric acid secretion. They inhibit acid secretion by up to 70% over a 24-h period. A major disadvantage of using these drugs is the development of tolerance that occurs within two weeks of uninterrupted daily intake[28
]. Thus, tolerance would be less concerning if they are to be used on an on-demand basis[29
]. PPIs have the advantage over H2
RA in controlling both basal and food-stimulated acid secretion producing a longer-lasting acid suppression in addition to the fact that tolerance has not been observed with PPIs.
Our pilot study has a few limitations. One is the open-label nature of the study. Although patients were randomized to different arms, they were aware of the arm they were randomized to. This may have created some bias especially if those patients were previously treated with the same medication class that they were assigned to. The sample size was also relatively small and further investigation based on a larger number of patients is necessary to corroborate our data. Our study duration was short, then again the purpose of our study was not to prove the efficacy of either of the two drugs, but rather to compare them.
The advantages of our study include the fact that it is the first to compare an H2RA to a PPI in the setting of on-demand therapy for NERD. We also showed response to on-demand therapy for both typical and atypical reflux symptoms. Finally, this is a “pure” on-demand study, in the sense that it was performed without a preceding continuous anti-secretory treatment period.
In conclusion, rabeprazole and ranitidine have been shown to be comparable in efficacy when given on-demand for the treatment of NERD. Both medications were associated with a statistically significant improved quality of life.