Kalaitzakis and Björnsson than omeprazole at 4 weeks (relative risk 1.14; 95% CI 1.10–1.18) and 8 weeks (relative risk 1.08: 95% CI 1.05, 1.10) (Edwards et al 2001). Another meta-analysis by the same investigators comparing esomeprazole with other PPIs for the healing of erosive esophagitis (Edwards et al 2006) included all the randomized trials summarized in Table 2. The authors concluded that esomeprazole demonstrated higher healing rates compared with standard dose PPIs at 4 weeks (relative risk 0.92; 95% CI 0.90,0.94; p < 0.00001) and at 8 weeks (relative risk 0.95; 95% CI 0.94.0.97; p < 0.00001) (Edwards et al 2006). Lastly, a meta-analysis of randomized clinical trials comparing esomeprazole with other PPIs in healing erosive esophagitis (Gralnek et al 2006), included 7 out of the 8 randomized studies summarized in Table 2 (Kahrilas et al 2000; Richter et al 2001; Castell et al 2002; Howden et al 2002; Gillessen et al 2004; Fennerty et al 2005; Labenz et al 2005b) as well as data from the manufacturer of esomeprazole included in the product information (esomeprazole vs omeprazole 20 mg od) and a study published in abstract form (esomeprazole 40 mg vs omeprazole 40 mg od). The last two mentioned studies have not been published and could therefore potentially create a bias in this context. In comparing healing rates of erosive esophagitis at 4 and 8 weeks, the authors found a 10% (relative risk 1.10; 95% CI 1.05–1.15) and 5% (relative risk 1.05; 95% CI 1.02–1.08) relative increase in the probability of healing, respectively, with esomeprazole vs alternative PPIs. Also, the authors found that esomeprazole conferred an 8% (relative risk 1.08; 95% CI 1.05–1.11) relative increase in the probability of GERD symptom relief at 4 weeks (Gralnek et al 2006). In this meta-analysis, the calculated numbers needed to treat (NNT) by Los Angeles grade of erosive esophagitis (grades A–D) were 50, 33, 14, and 8 (Gralnek et al 2006). This suggests that the beneﬁt of esomeprazole might be important in more severe erosive disease as indicated by the decreasing NNTs with increasing Los Angeles grade (Gralnek et al 2006). It is at the present time not entirely clear if these statistically significant differences are clinically signiﬁcant. Maintenance therapy of healed erosive GERD GERD usually relapses once drug therapy is discontinued, with about 80% having erosive GERD relapse after 6–12 months (DeVault and Castell 2005; Moayyedi and Talley 2006). Thus, many patients with GERD require long-term, possibly life-long, PPI therapy (Moayyedi and Talley 2006). However, a recent 658 study on discontinuation of PPIs in long-term users found that 20% of GERD patients were able to discontinue their PPIs without development of symptoms (Bjornsson et al 2006). Two double-blind, randomized studies have shown supe- riority of esomeprazole 40 mg, 20 mg, or 10 mg od to placebo in maintenance therapy of healed erosive GERD (Johnson et al 2001; Vakil et al 2001). The primary endpoint of both studies was endoscopically maintained healing 6 months after inclusion. In one of these, 375 patients with endoscopically healed esophagitis were randomized to receive esomeprazole 40 mg, 20 mg, 10 mg, or placebo od (Vakil et al 2001). After 6 months, signiﬁcantly (p < 0.001) more patients remained healed with esomeprazole 40 mg (87.9%), 20 mg (78.7%), or 10 mg (54.2%) than with placebo (29.1%) at endoscopy (Vakil et al 2001). In the other placebo-controlled study, 318 patients with endoscopically conﬁrmed healing of erosive GERD were randomized to receive esomeprazole 40 mg, 20 mg, 10 mg, or placebo od (Johnson et al 2001). After 6 months, healing was maintained in 93.6% of patients treated with esomeprazole 40 mg, 93.2% treated with esomeprazole 20 mg, and 57.1% treated with esomeprazole 10 mg; p < 0.001 vs 29.1% treated with placebo (Johnson et al 2001). Both of these studies reported that patients treated with esomeprazole had less severe heartburn than those treated with placebo. However, symptom maintenance data from these studies should be interpreted with caution as only those patients who maintained healing at the previous visit continued to the subsequent visits during the 6-month study period (Johnson et al 2001; Vakil et al 2001). Three clinical trials have compared esomeprazole with other PPIs as a maintenance therapy in GERD patients with healed erosive esophagitis (Table 3). Studies reported in Table 3 had a similar double-blind, randomized design and they included intention-to-treat analyses of endoscopy and symptom maintenance rates. Also, all three studies included patients who had endoscopy-conﬁrmed healing of their erosive GERD at baseline and follow-up endoscopy was performed at 3 and 6 months. The primary endpoint was endoscopic and symptom maintenance at 6 months. Secondary endpoints were separate endoscopic and symptom maintenance rates at 6 months (Lauritsen et al 2003; Labenz et al 2005a; Devault et al 2006). No comparative studies of esomeprazole vs omeprazole or rabeprazole in maintenance therapy of healed erosive GERD could be found. All three studies showed superiority of esomeprazole 20 mg to lansoprazole 15 mg or pantoprazole 20 mg od in the primary endpoint (Table 3). Furthermore, these studies showed superiority of esomeprazole 20 mg to lansoprazole Therapeutics and Clinical Risk Management 2007:3(4)