Abstract and Introduction
Background Dexlansoprazole is a new proton pump inhibitor (PPI) with a dual delayed-release system. Both dexlansoprazole and esomeprazole are an enantiomer of lansoprazole and omeprazole respectively. However, there is no head-to-head trial data or indirect comparison analyses between dexlansoprazole and esomeprazole.
Aim To compare the efficacy of dexlansoprazole with esomeprazole in healing erosive oesophagitis (EO), the maintenance of healed EO and the treatment of non-erosive reflux disease (NERD).
Methods Randomised Controlled Trials (RCTs) comparing dexlansoprazole or esomeprazole with either placebo or another PPI were systematically reviewed. Random-effect meta-analyses and adjusted indirect comparisons were conducted to compare the treatment effect of dexlansoprazole and esomeprazole using a common comparator. The relative risk (RR) and 95% confidence interval (CI) were calculated.
Results The indirect comparisons revealed significant differences in symptom control of heartburn in patients with NERD at 4 weeks. Dexlansoprazole 30 mg was more effective than esomeprazole 20 mg or 40 mg (RR: 2.01, 95% CI: 1.15–3.51; RR: 2.17, 95% CI: 1.39–3.38). However, there were no statistically significant differences between the two drugs in EO healing and maintenance of healed EO. Comparison of symptom control in healed EO was not able to be made due to different definitions used in the RCTs.
Conclusions Adjusted indirect comparisons based on currently available RCT data suggested significantly better treatment effect in symptom control of heartburn in patients with NERD for dexlansoprazole against esomeprazole. No statistically significant differences were found in other EO outcomes. However, these study findings need to be interpreted with caution due to small number of studies and other limitations.
Gastro-oesophageal reflux disease (GERD) is a common medical condition with abnormal reflux of gastric contents into the oesophagus. The most common symptoms of GERD include heartburn and regurgitation, which affects about 10–20% of the population in western countries; especially, 15–20% of the population in the US are suffering GERD symptoms at least weekly.
According to the manifestations of mucosal damage of the oesophagus confirmed by upper endoscopy, GERD is further categorised as erosive oesophagitis (EO) and non-erosive reflux disease (NERD) – the EO patients are diagnosed with a positive endoscopy, whereas the NERD patients only have the condition symptoms without the presence of oesophageal abnormalities by endoscopy. Among the patients with GERD, EO accounts for about 30% and NERD accounts for about 70%.
Esomeprazole is a proton pump inhibitor (PPI) that has been widely used for the treatment of GERD. Numerous randomised controlled trials (RCT) had demonstrated that it is effective and well tolerated in healing EO and relieving symptoms of NERD, as well as maintenance of healed EO.
Dexlansoprazole is the most recently developed PPI drug, which had been approved by the US Food and Drug Administration (FDA) on 30 January 2009. Dexlansoprazole has a novel dual delayed-release system for the treatment of heartburn associated with NERD, healing of all grades of EO, and maintenance of the healed EO.
A recent pH comparator study in healthy subjects showed that for the entire 24-h postdose period following a single dose of dexlansoprazole 60 mg, the average intragastric pH = 4.3, which was higher than the result observed following a single dose of esomeprazole 40 mg (average pH = 3.7), and the difference was statistically significant (P < 0.0001). Statistical significance (P = 0.003) was also found in the difference in the mean percentage of time with intragastric pH >4 with 58% for dexlansoprazole and 48% for esomeprazole. It is not clear, however, how these would mean in terms of clinical outcomes differences between the two treatments among the GERD patients.
There is no RCT, to date, directly compared dexlansoprazole with esomeprazole for efficacy in treatment of GERD. We therefore performed a systematic review and indirect comparison of RCTs to assess the relative effectiveness between dexlansoprazole and esomeprazole in the management of GERD.
In the situation of indirect comparison, we first need to identify studies of RCTs that directly compared dexlansoprazole with placebo and esomeprazole with placebo. By applying statistical methods, we then could use the placebo as a common comparator to perform an indirect comparison of dexlansoprazole and esomeprazole. The common comparator could also be another PPI drug.