Kalaitzakis and Björnsson In a double-blind, randomized, cross-over study in 35 patients with GERD symptoms, esomeprazole 40 mg od was compared with pantoprazole 40 mg od as to their effects on intraesophageal pH (Simon et al 2003). At baseline the median percentage of total time with pH <4.0 was 20.1% in the esomeprazole and 21.3% in the pantoprazole group. After 7 days of repeated administration, this time was reduced to 0.9% and 2.6% respectively, and the mean within-subject differences in mean 24-hour pH values between pre- and post-treatment values were 19.2% and 18.7% respectively. The Hodges- Lehmann estimate for the mean within-subjects differences in mean 24-hour pH between pre- and post-treatment values for the two PPIs was 2.86% and the corresponding 90% CI was within the equivalence range set at ± 10% (90% CI −2.27; 7.07) (Simon et al 2003). In another open-label randomized study, esomeprazole 40 mg od was compared with lansoprazole 30 mg od in 30 patients with complicated GERD (Frazzoni et al 2006). Normalization of total and supine nocturnal esophageal acid exposure was achieved in 75% vs 28% (p = 0.026) and 93% vs 50% (p = 0.012) of patients in the esomeprazole and the lansoprazole group, respectively (Frazzoni et al 2006). Erosive GERD Randomized trials evaluating the role of esomeprazole in healing of erosive GERD or maintenance therapy of healed erosive GERD were reviewed. Healing of erosive GERD Several clinical trials have compared esomeprazole with other PPIs in healing of erosive GERD (Table 2). Studies reported in Table 2 had a similar double-blind, randomized design; they included intention-to-treat analyses of healing rates, and, as a secondary endpoint, evaluation of therapy effect on GERD symptoms. Also, all studies included patients who had endoscopy-conﬁrmed erosive GERD at baseline. Follow-up endoscopy was performed at 4 weeks and at 8 weeks, except for one study in which patients underwent ﬁrst follow-up endoscopy at 4 or 6 weeks and second follow-up endoscopy at 8 or 10 weeks (Gillessen et al 2004). Although at least two randomized studies comparing esomeprazole with each of the other PPIs were identiﬁed, no comparative studies of esomeprazole vs rabeprazole in erosive GERD could be found. Five out of 8 studies showed that esomeprazole 40 mg od achieves better healing rates of erosive esophagitis after 4 and 8 weeks of treatment compared with omeprazole 20 mg, 656 lansoprazole 30 mg, or pantoprazole 40 mg od (Table 1). In these trials a total of 13,797 patients with erosive GERD were included. The greater efﬁcacy of esomeprazole over omeprazole, lansoprazole, or pantoprazole was consistent when adjusted for baseline severity of esophagitis according to the Los-Angeles classification. Furthermore, all of these studies showed that esomeprazole 40 mg od is more effective than omeprazole 20 mg, lansoprazole 30 mg, or pantoprazole 40 mg od in providing resolution of GERD- associated symptoms (Kahrilas et al 2000; Richter et al 2001; Castell et al 2002; Fennerty et al 2005; Labenz et al 2005b). Interestingly, all these studies were supported by the manufacturer of esomeprazole. However, 3/8 comparative studies, in which a total of 1659 patients were included, showed that there were no sta- tistically signiﬁcant differences in 4- or 8-week healing rates between esomeprazole 40 mg od and omeprazole 20 mg, lansoprazole 30 mg, or pantoprazole 40 mg od. One of these studies showed that healing rates with esomeprazole were signiﬁcantly higher than those with omeprazole at weeks 4 (60.8% vs 47.9%, p = 0.02) and 8 (88.4% vs 77.5%, p = 0.007) in patients with moderate to severe (Los Angeles grade C or D) erosive esophagitis at baseline but were not signiﬁcantly different for patients with mild (Los Angeles grade A or B) erosive esophagitis (Schmitt et al 2006). These studies reported similar efﬁcacy of esomeprazole compared to omeprazole, lansoprazole, or pantoprazole in GERD-related symptoms (Howden et al 2002; Gillessen et al 2004; Schmitt et al 2006). One out of three of these studies was supported by the manufacturer of esomeprazole, showing some beneﬁts of esomeprazole for patients with more severe esophagitis (Schmitt et al 2006). The other two were supported by the manufacturers of lansoprazole, showing no difference between lansoprazole and esome- prazole (Howden et al 2002), and by the manufacturer of pantoprazole, showing no difference between pantoprazole and esomeprazole (Gillessen et al 2004). Equivalence of esomeprazole 40 mg and pantoprazole 40 mg od in treating GERD-related symptoms in patients with erosive GERD was also reported in a double-blind randomized study in which 217 patients with esophagitis were included (Schol- ten et al 2003). In this trial no follow-up endoscopic evalu- ation was performed and, thus, no data on healing rates could be calculated (Scholten et al 2003). Helicobacter pylori infection has been shown to elevate the intragastric pH achieved by PPIs (Verdu et al 1995; Labenz et al 1996). In a study with pantoprazole, it has also been proposed that this increased efﬁcacy of PPIs in Therapeutics and Clinical Risk Management 2007:3(4)