Advertisement

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

      This paper is only available as a PDF. To read, Please Download here.

      Abstract

      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 ≥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.

      Keywords

      To read this article in full you will need to make a payment

      Purchase one-time access:

      Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online access
      One-time access price info
      • For academic or personal research use, select 'Academic and Personal'
      • For corporate R&D use, select 'Corporate R&D Professionals'

      Subscribe:

      Subscribe to Clinical Therapeutics
      Already a print subscriber? Claim online access
      Already an online subscriber? Sign in
      Institutional Access: Sign in to ScienceDirect

      References

        • Howard PJ
        • Heading RC
        Epidemiology of gastro-esophageal reflux disease.
        World J Surg. 1992; 16: 288-293
        • Galmiche JP
        • Letessier E
        • Scarpignato C
        Treatment of gastro-oesophageal reflux disease in adults.
        Br Med J. 1998; 316: 1720-1723
        • Castell DO
        • Johnston BT
        Gastro-esophageal reflux disease. Current strategies for patient management.
        Arch Fam Med. 1996; 5: 221-227
        • Wienbeck M
        • Barnet J
        Epidemiology of reflux disease and reflux oesophagitis.
        Scand J Gastroenterol. 1989; 24: 7-13
        • Johanson JF
        Epidemiology of esophageal and supraesophageal reflux injuries.
        Am J Med. 2000; 108: 99S-103S
        • Spechler SJ
        Epidemiology and natural history of gastro-oesophageal reflux disease.
        Digestion. 1992; 51 (Suppl 1): 24-29
        • Katz PO
        Pathogenesis and management of gastroesophageal reflux disease.
        J Clin Gastroenterol. 1991; 13 (Suppl 2): S6-S15
        • Thomson AB
        • Chiba N
        • Armstrong D
        • et al.
        The Second Canadian Gastroesophageal Reflux Disease Consensus: Moving forward to new concepts.
        Can J Gastroenterol. 1998; 12: 551-556
        • Earnest DL
        • Robinson M
        Treatment advances in acid secretory disorders: The promise of rapid symptom relief with disease resolution.
        Am J Gastroenterol. 1999; 94 (Suppl 11): S17-S24
        • Holtmann G
        • Layer P
        • Goebell H
        Are proton pump inhibitors superior to H2-receptor antagonists within the scope of H. pylori eradication therapy? Meta analysis of current parallel group comparisons [in German].
        Z Gastroenterol. 1996; 34: 267-272
        • Chiba N
        Proton pump inhibitors in acute healing and maintenance of erosive or worse esophagitis: A systematic overview.
        Can J Gastroenterol. 1997; 11 (Suppl B): 66B-73B
        • Lampkin TA
        • Ouellet D
        • Hak LJ
        • Dukes GE
        Omeprazole: A novel antisecretory agent for the treatment of acid-peptic disorders.
        DICP. 1990; 24: 393-402
        • Miettinen OS
        Theoretical epidemiology.
        in: 1st ed. Principles of Occurrence Research in Medicine. Delmar Publishers, New York1985: 155-183
        • Greenland S
        • Rothman KJ
        Testing homogeneity.
        in: Rothman KJ Greenland S 2nd ed. Modern Epidemiology. Williams & Wilkins, Philadelphia1998: 275-277
        • Blum AL
        Omeprazole is superior to ranitidine in curing and further managing patients with heartburn.
        Gut. 1997; 41 (Abstract F14): A202
        • Hazenberg BP
        • Geraedts AAM
        • de Groot GH
        Omeprazole versus ranitidine in the treatment of symptomatic mild reflux oesophagitis. A Dutch multi-centre trial.
        Gut. 1995; (Abstract W26): S7
        • Cloud ML
        • Enas N
        • Humphries TJ
        • Bassion S
        • Rabeprazole Study Group
        Rabeprazole in treatment of acid peptic diseases: Results of three placebo-controlled dose-response clinical trials in duodenal ulcer, gastric ulcer, and gastroesophageal reflux disease (GERD).
        Dig Dis Sci. 1998; 43: 993-1000
        • Earnest DL
        • Dorsch J
        • Jones DE
        • et al.
        A placebo-controlled dose-ranging study of lansoprazole in the management of reflux esophagitis.
        Am J Gastroenterol. 1998; 93: 238-243
        • Hetzel DJ
        • Dent J
        • Reed WD
        • et al.
        Healing and relapse of severe peptic esophagitis after treatment with omeprazole.
        Gastroenterology. 1988; 95: 903-912
        • McCarthy JH
        • Dent J
        • Hetzel DJ
        • et al.
        Omeprazole in the treatment of reflux oesophagitis.
        Aust New Zealand J Med. 1986; 16 (Abstract): 595
        • Sontag SJ
        • Hirschowitz BI
        • Holt S
        • et al.
        Two doses of omeprazole versus placebo in symptomatic erosive esophagitis: The U.S. multicenter study.
        Gastroenterology. 1992; 102: 109-118
        • Richter JE
        • Peura D
        • Benjamin SB
        • et al.
        Efficacy of omeprazole for the treatment of symptomatic acid reflux disease without esophagitis.
        Arch Intern Med. 2000; 160: 1810-1816
        • Richter JE
        • Campbell DR
        • Kahrilas PJ
        • et al.
        Lansoprazole compared with ranitidine for the treatment of nonerosive gastroesophageal reflux disease.
        Arch Intern Med. 2000; 160: 1803-1809
        • Maton PN
        • Orlando R
        • Joelsson B
        Efficacy of omeprazole versus ranitidine for symptomatic treatment of poorly responsive acid reflux disease—a prospective, controlled trial.
        Aliment Pharmacol Ther. 1999; 13: 819-826
        • Hatlebakk JG
        • Hyggen A
        • Madsen PH
        • et al.
        Heartburn treatment in primary care: Randomised, double blind study for 8 weeks.
        Br Med J. 1999; 319: 550-553
        • Lundell L
        • Backman L
        • Ekstrom P
        • et al.
        Omeprazole or high-dose ranitidine in the treatment of patients with reflux oesophagitis not responding to ‘standard doses’ of H2-receptor antagonists.
        Aliment Pharmacol Ther. 1990; 4: 145-155
        • Dekkers CP
        • Beker JA
        • Thjodleifsson B
        • et al.
        • European Rabeprazole Study Group
        Double-blind comparison of rabeprazole 20 mg vs. omeprazole 20 mg in the treatment of erosive or ulcerative gastrooesophageal reflux disease.
        Aliment Pharmacol Ther. 1999; 13: 49-57
        • Delchier JC
        • Cohen G
        • Humphries TJ
        Rabeprazole, 20 mg once daily or 10 mg twice daily, is equivalent to omeprazole, 20 mg once daily, in the healing of erosive gastrooesophageal reflux disease.
        Scand J Gastroenterol. 2000; 35: 1245-1250
        • Corinaldesi R
        • Valentini M
        • Belaiche J
        • et al.
        Pantoprazole and omeprazole in the treatment of reflux oesophagitis: A European multicentre study.
        Aliment Pharmacol Ther. 1995; 9: 667-671
        • Mossner J
        • Holscher AH
        • Herz R
        • Schneider A
        A double-blind study of pantoprazole and omeprazole in the treatment of reflux oesophagitis: A multicenter trial.
        Aliment Pharmacol Ther. 1995; 9: 321-326
        • Mee AS
        • Rowley JL
        Rapid symptom relief in reflux oesophagitis: A comparison of lansoprazole and omeprazole.
        Aliment Pharmacol Ther. 1996; 10: 757-763
        • Mulder CJ
        • Dekker W
        • Gerretsen M
        Lansoprazole 30 mg versus omeprazole 40 mg in the treatment of reflux oesophagitis grade II, III and IVa (a Dutch multicentre trial): Dutch Study Group.
        Eur J Gastroenterol Hepatol. 1996; 8: 1101-1106
        • Rampal P
        • Courrier A
        • Lemerez M
        • et al.
        Efficacy and safety of lansoprazole 30 mg versus omeprazole for 21 days treatment of acute esophagitis.
        Gastroenterology. 1995; 108 (Abstract): A200
        • Castell DO
        • Richter JE
        • Robinson M
        • et al.
        • The Lansoprazole Group
        Efficacy and safety of lansoprazole in the treatment of erosive reflux esophagitis.
        Am J Gastroenterol. 1996; 91: 1749-1757
        • Farley A
        • Wruble LD
        • Humphries TJ
        • Rabeprazole Study Group
        Rabeprazole versus ranitidine for the treatment of erosive gastroesophageal reflux disease: A double blind, randomized clinical trial.
        Am J Gastroenterol. 2000; 95: 1894-1899
        • Koop H
        • Schepp W
        • Dammann HG
        • et al.
        Comparative trial of pantoprazole and ranitidine in the treatment of reflux esophagitis. Results of a German multicenter study.
        J Clin Gastroenterol. 1995; 20: 192-195
        • Porro GB
        • Pace F
        • Peracchia A
        • et al.
        Short-term treatment of refractory reflux esophagitis with different doses of omeprazole or ranitidine.
        J Clin Gastroenterol. 1992; 15: 192-198
        • Havelund T
        • Laursen LS
        • Skoubo-Kristensen E
        • et al.
        Omeprazole and ranitidine in treatment of reflux oesophagitis: Double-blind comparative trial.
        Br Med J (Clin Res Ed). 1988; 296: 89-92
        • Klinkenberg-Knol EC
        • Jansen JM
        • Festen HP
        • et al.
        Double-blind multicentre comparison of omeprazole and ranitidine in the treatment of reflux oesophagitis.
        Lancet. 1987; 1: 349-351
        • Richter JE
        • Sabesin SM
        • Kogut DG
        • et al.
        Omeprazole versus ranitidine or ranitidine/metoclopramide in poorly responsive symptomatic gastroesophageal reflux disease.
        Am J Gastroenterol. 1996; 91: 1766-1772
        • Venables TL
        • Newland RD
        • Patel AC
        • et al.
        Omeprazole 10 milligrams once daily, omeprazole 20 milligrams once daily or ranitidine 150 milligrams twice daily, evaluated as initial therapy for the relief of symptoms of gastro-oesophageal reflux disease in general practice.
        Scand J Gastroenterol. 1997; 32: 965-973
        • Robinson M
        • Decktor DL
        • Maton PN
        • et al.
        Omeprazole is superior to ranitidine plus metoclopramide in the short-term treatment of erosive oesophagitis.
        Aliment Pharmacol Ther. 1993; 7: 67-73
        • Sandmark S
        • Carlsson R
        • Fausa O
        • Lundell L
        Omeprazole and ranitidine in the treatment of reflux esophagitis: Results of a double-blind, randomized, Scandinavian multicenter study.
        Scand J Gastroenterol. 1988; 23: 625-632
        • The Italian Reflux Oesophagitis Study Group
        Omeprazole produces significantly greater healing of erosive or ulcerative reflux oesophagitis than ranitidine.
        Eur J Gastroenterol Hepatol. 1991; 3: 511-517
        • Vantrappen G
        • Rutgeerts L
        • Schurmans P
        • Coenegrachts JL
        Omeprazole (40 mg) is superior to ranitidine in short-term treatment of ulcerative reflux esophagitis.
        Dig Dis Sci. 1988; 33: 523-529
        • Zeitoun R
        • Rampal P
        • Barbier P
        • et al.
        Omeprazole (20 mg daily) compared to ranitidine (150 mg twice daily) in the treatment of esophagitis caused by reflux. Results of a double-blind randomized multicenter trial in France and Belgium [in French].
        Gastroenterol Clin Biol. 1989; 3: 457-462
        • Bardhan KD
        • Hawkey CJ
        • Long RG
        • et al.
        • UK Lansoprazole Clinical Research Group
        Lansoprazole versus ranitidine for the treatment of reflux oesophagitis.
        Aliment Pharmacol Ther. 1995; 9: 145-151
        • Feldman M
        • Harford WV
        • Fisher RS
        • et al.
        • Lansoprazole Study Group
        Treatment of reflux esophagitis resistant to H2-receptor antagonists with lansoprazole, a new H+/K+-ATPase inhibitor: A controlled, double-blind study.
        Am J Gastroenterol. 1993; 88: 1212-1217
        • Jansen JB
        • Hazenberg BP
        • Tan TG
        • et al.
        Lansoprazole (30 mg) is more effective than high-dose ranitidine (2 × 300 mg) in moderate to severe reflux esophagitis. A Dutch multicenter trial.
        Gastroenterology. 1996; 110 (Abstract): A143
        • Plein K
        • Stolte M
        • Fuchs W
        • et al.
        Lansoprazole vs. ranitidine efficacy in healing acute reflux esophagitis and influence on hyperregenerative esophagopathy.
        Gut. 1995; 37 (Abstract): A38
        • Robinson M
        • Sahba B
        • Avner D
        • et al.
        • Multicentre Investigational Group
        A comparison of lansoprazole and ranitidine in the treatment of erosive oesophagitis.
        Aliment Pharmacol Ther. 1995; 9: 25-31
        • Sontag SJ
        • Kogut DG
        • Fleischmann R
        • et al.
        Lansoprazole heals erosive reflux esophagitis resistant to histamine H2-receptor antagonist therapy.
        Am J Gastroenterol. 1997; 92: 429-437
        • Humphries TJ
        • Dekkers CPM
        • Beker JA
        • et al.
        Rabeprazole vs omeprazole for maintenance therapy of healed erosive GERD: Results of a 1-year multicenter trial.
        Am J Gastroenterol. 1998; 93 (Abstract 30): 1616
        • Carling L
        • Axelsson C
        • Forsell H
        • et al.
        Lansoprazole versus omeprazole in long term maintenance treatment of reflux oesophagitis: A Scandinavian multicentre trial.
        Gut. 1996; 39 (Abstract 1036): A182
        • Baldi F
        • Bardhan KD
        • Borman BC
        • et al.
        Lansoprazole maintains healing in patients with reflux esophagitis.
        Gastroenterology. 1996; 110 (Abstract): A55
        • Breiter J
        • Birbara C
        • Niecestro R
        • et al.
        Rabeprazole prevents recurrence of pathology and symptoms in patients with healed erosive or ulcerative gastroesophageal reflux disease.
        Gastroenterology. 1999; 116 (Abstract 60552): A128
        • Venables TL
        • Newland RD
        • Patel AC
        • et al.
        Maintenance treatment of gastroesophageal reflux disease: A placebo-controlled evaluation of 10 milligrams omeprazole once daily in general practice.
        Scand J Gastroenterol. 1997; 32: 627-632
        • Sontag S
        • Robinson M
        • Roufail W
        • et al.
        Daily omeprazole is needed to maintain healing in erosive esophagitis.
        Am J Gastroenterol. 1992; 87 (Abstract 65): 1258
        • Laursen LS
        • Havelund T
        • Bondesen S
        • et al.
        Omeprazole in the long-term treatment of gastro-oesophageal reflux disease. A double-blind randomized dose-finding study.
        Scand J Gastroenterol. 1995; 30: 839-846
        • Bate CM
        • Booth SN
        • Crowe JP
        • et al.
        • Solo Investigator Group
        Omeprazole 10 mg or 20 mg once daily in the prevention of recurrence of reflux oesophagitis.
        Gut. 1995; 36: 492-498
        • Sontag SJ
        • Kogut DG
        • Fleischmann R
        • et al.
        • Lansoprazole Maintenance Study Group
        Lansoprazole prevents recurrence of erosive reflux esophagitis previously resistant to H2-RA therapy.
        Am J Gastroenterol. 1996; 91: 1758-1765
        • Robinson M
        • Lanza F
        • Avner D
        • Haber M
        Effective maintenance treatment of reflux esophagitis with low-dose lansoprazole. A randomized, double-blind, placebo-controlled trial.
        Ann Intern Med. 1996; 124: 859-867
        • Vigneri S
        • Termini R
        • Leandro G
        • et al.
        A comparison of five maintenance therapies for reflux esophagitis.
        N Engl J Med. 1995; 333: 1106-1110
        • Lundell L
        • Backman L
        • Ekstrom P
        • et al.
        Prevention of relapse of reflux esophagitis after endoscopic healing: The efficacy and safety of omeprazole compared with ranitidine.
        Scand J Gastroenterol. 1991; 26: 248-256
        • Hallerback B
        • Unge P
        • Carling L
        • et al.
        • Scandinavian Clinics for United Research Group
        Omeprazole or ranitidine in long-term treatment of reflux esophagitis.
        Gastroenterology. 1994; 107: 1305-1311
        • Dent J
        • Yeomans ND
        • Mackinnon M
        • et al.
        Omeprazole v ranitidine for prevention of relapse in reflux oesophagitis. A controlled double blind trial of their efficacy and safety.
        Gut. 1994; 35: 590-598
        • Gough AL
        • Long RG
        • Cooper BT
        • et al.
        Lansoprazole versus ranitidine in the maintenance treatment of reflux oesophagitis.
        Aliment Pharmacol Ther. 1996; 10: 529-539
        • Goeree R
        • O'Brien B
        • Hunt R
        • et al.
        Economic evaluation of long term management strategies for erosive oesophagitis.
        Pharmacoeconomics. 1999; 16: 679-697
        • Chiba N
        • De Gara CJ
        • Wilkinson JM
        • Hunt RH
        Speed of healing and symptom relief in grade II to IV gastroesophageal reflux disease: A meta-analysis.
        Gastroenterology. 1997; 112: 1798-1810
        • Bell NJ
        • Hunt RH
        Role of gastric acid suppression in the treatment of gastrooesophageal reflux disease.
        Gut. 1992; 33: 118-124