Nexium (esomeprazole) First PPI to Demonstrate Sustained Reduction in Peptic Ulcer Re-Bleeding in Large Scale Multinational Placebo-Controlled Clinical Study

Sustained 30 Day Efficacy Profile Reported with Reduced Follow-Up Blood Transfusion and Endoscopic Intervention

Vienna, 22nd October 2008- An intravenous (i.v.) infusion of esomeprazole has demonstrated a clinically important reduction in peptic ulcer re-bleeding according to data presented today at the United European Gastroenterology Week (UEGW).  In a large scale investigational study, more than 700 patients received oral esomeprazole following the i.v. administration of either esomeprazole or placebo. To date, no drugs are formally approved for the prevention of re-bleeding after primary endoscopic haemostasis (cessation of bleeding) for a bleeding peptic ulcer.

Peptic ulcers are typically caused by infection with Helicobacter pylori or the long-term use of medicines such as non-steroidal anti-inflammatory drugs (NSAIDs) or low-dose aspirin. If after treatment, a peptic ulcer re-bleeds there is an increased risk of morbidity and mortality9 and associated healthcare costs. 
 
The results of the Peptic Ulcer Bleed (PUB) Study demonstrated that statistically significantly fewer patients treated with esomeprazole experienced ulcer re-bleeding compared with placebo both at 72 hours (5.9% versus 10.3%, P=0.026) and at seven days (7.2% versus 12.9%, P=0.0096).1,2,3 The study also examined sustainability of treatment effect with esomeprazole, which was shown to significantly reduce the number of patients re-bleeding by almost half compared to placebo (7.7% versus 13.6%, P=0.0092) over a  30 day period.1,2,3 

In all cases, patients receiving esomeprazole in the study required significantly fewer interventions by day 30, with 6.4% needing endoscopic retreatment compared with 11.6% in the placebo group (P=0.037).3 In addition, 589 units of blood in the esomeprazole treatment group were transfused to patients compared with 935 units in total in the placebo group.3 Numerically fewer patients required surgical intervention compared to the placebo group. Overall, esomeprazole patients required significantly fewer days in hospital due to re-bleeding compared to the placebo group (284 days versus 500 days, P=0.008).3

 “This is a very important study for physicians and patients, as it not only demonstrates how ulcer re-bleeding after endoscopic treatment can be better controlled, but also provides a high level of reassurance in an at-risk population where needs are currently unmet” said Professor Joseph Sung, Institute of Digestive Diseases/Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Prince of Wales Hospital, Hong Kong, China.

Professor Sung continued “To date, successful studies in this area have not focused on populations from such wide geography and ethnic backgrounds, or indeed followed outcomes for 30 days – the time period in which the problems associated with the recurrence of bleeding can be most acute. This helps us learn a great deal about the clinical outcomes that should be targeted in the management of peptic ulcer bleed moving forward”.

Professor Alan Barkun, Professor and Director, Division of Gastroenterology, McGill University, Montreal, Quebec, Canada commented, “The results of the PUB study should bring about a step-change in clinical practice as they demonstrate how re-bleeding can be prevented in a diverse population, and also point to the potential for cost savings through reduced repeat endoscopic treatment and transfusion.  This is important in terms of patient outcomes and will also be of interest to healthcare budget holders.”

In the PUB Study,1,2,3,4 767 patients from 16 countries across Europe, Africa and Asia,9 who had received successful endoscopic treatment for PUB were randomized to first receive an i.v. infusion of esomeprazole 80mg over 30 minutes followed by 8mg i.v./hour for 72 hours, and then receive 40mg oral treatment for 27 days.9 A parallel placebo-controlled group received an i.v. infusion of placebo before the same 27-day period of oral treatment with esomeprazole.9 

The PUB study was sponsored by AstraZeneca. AstraZeneca is a major international healthcare company engaged in research, development, manufacturing and marketing of prescription pharmaceuticals and supplier for healthcare services. AstraZeneca is one of the world's leading pharmaceutical companies with healthcare sales of US $29.55 billion and is a leader in gastrointestinal, cardiovascular, neuroscience, respiratory, oncology and infection product sales. AstraZeneca is listed in the Dow Jones Sustainability Index (Global) as well as the FTSE4Good Index.

 


For further enquiries please contact:
James Harper Simon Grist/Joanna Williams
AstraZeneca Hill & Knowlton (UK) Ltd
+44 (0)1582 836 000 (direct)   +44 (0)207 413 3081/3795 (direct)
+44 (0)7714 322796 (mobile)  +44 (0) 774 382 29 245 (mobile) 
james.harper@astrazeneca.com  simon.grist@hillandknowlton.com 
      joanna.williams@hillandknowlton.com

 

PUB

• Peptic Ulcer Bleeding (PUB) is a potentially life-threatening event that occurs as a complication of peptic ulcer disease, usually perforation.

• PUB occurs when the ulcer erodes into an underlying blood vessel. The resulting blood loss can be significant as clotting can be impaired in the acidic environment. If after treatment, a peptic ulcer re-bleeds there is an increased risk of morbidity and mortality9,12,13 and associated healthcare costs13,14,15,16


Nexium® (esomeprazole)
• Nexium® is not yet approved for management of Peptic Ulcer Bleeding

• Nexium® is approved in Europe for indication in adults for treating frequent, persistent heartburn and other symptoms associated with acid reflux (GORD) and for the healing and maintenance of erosive oesophagitis .

• Nexium® is indicated in the EU for healing of gastric ulcers associated with NSAID therapy and prevention of gastric and duodenal ulcers associated with NSAID therapy in patients at risk.17 Nexium® is also indicated for healing of Helicobacter-pylori associated duodenal ulcers and prevention of peptic ulcers relapse in patients with Helicobacter-pylori associated ulcers17


About United European Gastroenterology Week (UEGW) 
The United European Gastroenterology Federation, with the active involvement of all member societies, organises an annual meeting to learn about the latest advances in the fields of gastroenterology, hepatology, endoscopy and gastrointestinal surgery. UEGW 2008 is in Vienna from the 18th-22nd October

References
  Sung J, Lau J, Barkun A et al. Intravenous esomeprazole for prevention of peptic ulcer re-bleeding: A multi-national, double-blind, placebo-controlled, randomised study. Abstract presented at UEGW 2008
  Barkun A, Adam V, Sung J et al. High-dose intravenous esomeprazole in peptic ulcer bleeding: New clinical data applied to a European cost-effectiveness analysis. Abstract presented at UEGW 2008
  Barkun A, Sung J, Kuipers E et al. Intravenous esomeprazole for prevention of peptic ulcer re-bleeding in a predominantly Caucasian population: Results on clinical benefits and hospital resource use. Abstract presened at UEGW 2008
  Kuipers E, Sung J, Barkun A et al. High-dose intravenous esomeprazole is safe and well tolerated in patients with peptic ulcer bleeding. Abstract presented at UEGW 2008
  Van Rensburg C, Racz I, Bailey R et al. Prevention of peptic ulcer rebleeding using continuous infusion of pantoprazole versus rantidine: A multicenter multinational, randomized, double-blind parallel group comparison. Canadian Journal of Gastroenterology 2004 (e-supplement): Abs 149. 
  Jensen D, Pace S, Soffer E et al. 315 Study Group. Continuous infusion of pantoprazole versus ranitidine for prevention of ulcer rebleeding: A U.S. multicenter, randomized, double-blind study. American Journal of Gastroenterology 2006; 101:1991
  Hasselgren G, Lind T, Lundell L et al. Continuous infusion of omeprazole in elderly patients with peptic ulcer bleeding. Results of a placebo-controlled study.  Scandinavian Journal of Gastroenterology 1997;32 (4):328-33. 
  Schaffalitzky  de Muckadell O, Havelund T, Harding H et al. Effect of omeprazole on the outcome of endoscopically treated bleeding peptic ulcers. Randomized double-blind placebo-controlled multicentre study. Scandianvian Journal of Gastroenterology 1997;32 (4):320-7.
  Sung J, Mössner J, Barkun et al. on behalf of the PUB Study Group. Intravenous esomeprazole for prevention of peptic ulcer rebleeding: rationale / design of the Peptic Ulcer Bleed Study, Alimentary Pharmacology & Therapeutics, 2008; 27, 666-667.
  Lanas A, Scheiman J. Low-dose aspirin and upper gastrointestinal damage: epidemiology, prevention and treatment. Current Medical Research and Opinion 2007;23(1):163-73.
  Scheiman J, Yeomans N, Talley N et al. Summing the risk of NSAID therapy. The Lancet 2007; 369:1580-1581.
  Holtman G, Howden W. Review article: management of peptic ulcer bleeding – the roles of proton pump inhibitors and H.pylori eradication. Ailmentary Pharmacology & Therapeutics 2004; 19 (Suppl 1): 66-70.
  Van Leerdam M, Vreeburg E, Rauws E at al. Acute upper GI bleeding: Did anything change? Time trend analysis of incidence and outcome of acute upper GI bleeding between 1993/4 and 2000. American Journal of Gastroenterology, 2003; 98(7):1494-9.
  Barkun A et al.  High-dose intravenous proton pump inhibition following endoscopic therapy in the acute management of patients with bleeding peptic ulcers in the USA and Canada: a cost-effectiveness analysis. Aliment Pharmacol Ther 2004; 19: 591-600.
  McQuaid K, Laine L. Systematic review and meta-analysis of adverse events of low-dose aspirin and clopidogrel in randomized controlled trials. American Journal of Medicine 2006;119(8):624-38.
  Barkun A, Herba K, Adam V et al. The cost-effectiveness of high-dose oral proton pump inhibition after endoscopy in the acute treatment of peptic ulcer bleeding.  Aliment Pharmacol Ther 2004; 20: 195–202.
 

Posted: October 2008

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