Healing and relapse rates in gastroesophageal reflux disease treated with the newer proton-pump inhibitors lansoprazole, rabeprazole, and pantoprazole compared with omeprazole, ranitidine, and placebo: evidence from randomized clinical trials.
BACKGROUND
The older proton pump inhibitor (PPI) omeprazole and the newer PPIs lansoprazole, rabeprazole, and pantoprazole are approved for the acute and maintenance treatment of gastroesophageal reflux disease (GERD).


OBJECTIVE
On the basis of the results of randomized clinical trials, this study sought to estimate healing and relapse rates in acute and maintenance treatment of GERD with the newer PPIs compared with omeprazole, the histamine2-receptor antagonist ranitidine (the most frequent non-PPI comparator in studies of PPIs), and placebo.


METHODS
A search of MEDLINE was conducted to identify randomized, controlled clinical trials that included a PPI in > or =1 treatment arm and assessed the healing of erosive esophagitis endoscopically. The primary outcome for studies of acute therapy was healing rate, and the primary outcome for studies of maintenance therapy was relapse rate.


RESULTS
Fifty-three studies were identified, of which 38 involved acute therapy (12 excluded) and 15 maintenance therapy. None of the studies of pantoprazole met the inclusion criteria for maintenance therapy. The 8-week overall healing rate ratios in the comparison of newer PPIs with omeprazole 20 mg/d were as follows: lansoprazole 30 mg/d, 1.02 (95% CI, 0.98-1.06): rabeprazole 20 mg/d, 0.93 (95% CI, 0.87-1.00); and pantoprazole 40 mg/d, 0.98 (95% CI, 0.90-1.07). In the comparison of any PPI with ranitidine 300 mg/d, the ratios were as follows: lansoprazole, 1.62 (95% CI, 1.46-1.76); rabeprazole, 1.36 (95% CI, 1.20-1.54); pantoprazole, 1.60 (95% CI, 1.33-1.96); and omeprazole, 1.58 (95% CI, 1.41-1.78). Relapse rates over 1 year of treatment were similar between lansoprazole and rabeprazole. Compared with ranitidine, there were statistically significant differences in the rates of resolution of heartburn symptoms (P < 0.002), ulcer healing (P < 0.05), and relapse (P < 0.01). Similar results were seen in the comparison of PPIs with placebo in terms of rates of resolution of heartburn symptoms (P < 0.01), ulcer healing (P < 0.001), and relapse (P < 0.006).


CONCLUSIONS
In this study, the newer PPIs were of similar efficacy to omeprazole in terms of heartburn control, healing rates, and relapse rates. All the PPIs were superior to ranitidine and placebo in healing erosive esophagitis and decreasing relapse rates.
Caro
J J
JJ
Division of General Internal Medicine, McGill University, Montreal, Quebec, Canada. jcaro@caroresearch.com
Salas
M
M
Ward
A
A
D053799:2-Pyridinylmethylsulfinylbenzimidazoles; D000897:Anti-Ulcer Agents / Q000627:therapeutic use*; D001562:Benzimidazoles / Q000627:therapeutic use; D005764:Gastroesophageal Reflux / Q000188:drug therapy*; D006801:Humans; D064747:Lansoprazole; D009853:Omeprazole / Q000031:analogs & derivatives* / Q000627:therapeutic use; D000077402:Pantoprazole; D064750:Rabeprazole; D016032:Randomized Controlled Trials as Topic; D011899:Ranitidine / Q000627:therapeutic use; D013454:Sulfoxides / Q000627:therapeutic use; D016896:Treatment Outcome
D053799:2-Pyridinylmethylsulfinylbenzimidazoles; D000897:Anti-Ulcer Agents; D001562:Benzimidazoles; D013454:Sulfoxides; D064747:Lansoprazole; D064750:Rabeprazole; D011899:Ranitidine; D000077402:Pantoprazole; D009853:Omeprazole