To print: Select File and then Print from your browser's menu --------------------------------------------------------------------------------------- Title: Clinical Data Suggest That in Subjects Taking Cardio-Protective Low-Dose Aspirin, Celecoxib Causes Significantly Fewer Gastroduodenal Endoscopic Ulcers Than Naproxen URL: http://www.pslgroup.com/dg/1F3A62.htm Doctor's Guide June 24, 2006
Data presented at the Annual European League Against Rheumatism (EULAR) Meeting AMSTERDAM, THE NETHERLANDS -- June 24, 2006 -- New clinical data show that for healthy subjects taking cardio-protective low-dose aspirin who also need arthritis pain relief medication, Celebrex (celecoxib) may be a better option than the commonly used non-selective (ns) NSAID naproxen.1 The study of 662 healthy subjects revealed over three times more people taking naproxen (500 mg twice daily) and aspirin (81 mg daily) had endoscopic gastric and/or duodenal ulcers compared with those taking Celebrex (200 mg twice daily) and aspirin (81 mg daily), (25.3% vs. 7%).1 * This difference was statistically significant. "This study begins to address an important topic as a high percentage of the population takes aspirin for cardiovascular protection, and also take pain relief treatments for their arthritis. Studies like this one highlight the importance of providing physicians with information regarding the recognition of patients at higher risk for developing GI problems associated with their anti-inflammatory therapies," commented lead-investigator Jay Goldstein MD. Professor of Medicine, University of Illinois at Chicago. The cardio-protective effects of low-dose aspirin (<325 mg daily) are well established, and it is widely used to help prevent blood clots and heart attacks.2-5 However, both aspirin and naproxen are associated with increased risk of GI complications such as stomach ulcers and bleeding, due to inhibition of the COX-1 enzyme.6-8 Celebrex specifically targets the COX-2 enzyme, thus reducing inflammation and pain, without blocking the beneficial effects of the COX-1 enzyme on the stomach and intestine when used at therapeutic doses. Importantly, this study demonstrates the upper GI advantage of the COX-2 Celebrex compared with ns-NSAIDs is maintained even with concomitant aspirin use. The GI benefit of Celebrex with cardio-protective aspirin is additionally supported by a similar trial where patients were taking higher doses of aspirin (325 mg daily). In this study, significantly less (37%) gastric and/or duodenal endoscopic ulcers were observed in healthy subjects taking Celebrex (200 mg daily) and concomitant aspirin compared to those taking naproxen (500 mg twice daily) and aspirin.9** While there is an increased GI risk with use of Celebrex or naproxen in combination with aspirin, than with aspirin alone, this risk is significantly less with Celebrex compared to naproxen. EULAR Data Highlights Need for GI Safety of NSAID Users Gastroprotection gap an increasing danger for elderly NSAID users The importance of GI safety for patients taking pain relief medications has been emphasized in a further study presented at EULAR indicating that an increasing number of elderly users of NSAIDs are left without appropriate gastroprotection; approximately 35% of NSAID users in the US in 2005.10 The research suggests that if this trend is left unchanged, morbidity and mortality from NSAID-related complications may increase.10 GI benefit -- evidence for COX-2s The use of COX-2 selective inhibitors as a treatment strategy to close the gastroprotection gap is supported by a review of existing evidence suggesting that compared with ns-NSAIDs, COX-2 use resulted in fewer symptomatic ulcers and bleeds, endoscopically detected ulcers, and discontinuation for adverse events or GI adverse events, in data presented at EULAR by Dr. Andrew Moore.11 Poor patient compliance undermines GI benefit of ns-NSAID + PPI The treatment strategy of combining ns-NSAIDs plus gastroprotective agents (GPA) like proton pump inhibitors (PPI) may not provide optimal GI protection for chronic ns-NSAID users due to lack of compliance, according to research presented at EULAR.12 The study found compliance of ns-NSAID and GPA (defined as a >/= 80% overlap in treatment) decreased from 68% (duration of 3-12 months) down to 46% (duration of 2 years or longer) -- with preliminary data including non-adherence at the 80% level within the last 6 months, increasing the likelihood of a GI event by 67% (CI 95% 0.93-2.99).12*** "The pain treatment landscape has changed over the last 18 months with an increased sensitivity and confusion around the risks and benefits of treatment options. All treatments contain some risk of adverse as well as beneficial effects, and it is important for doctors and patients to discuss suitable treatments to ensure patients receive optimal care," commented Andrew Moore DSc, Director of Research, Pain Research Unit, University of Oxford. Pfizer is supporting ongoing research to further understand the GI profile of Celebrex compared to other NSAIDs. Currently, enrolment has begun on a large-scale trial know as CONDOR (Celecoxib versus Omeprazole aNd Dicolfenac for at-risk Osteoarthritis and Rheumatoid arthritis patients), a clinical study to assess both upper and lower GI safety of Celebrex versus diclofenac and omeprazole. Approximately 4400 higher risk OA and RA patients will be randomized to receive Celebrex (200 mg bid) or diclofenac (75 mg bid) and the proton pump inhibitor omeprazole (20 mg qd), for 6 months, with the primary endpoint of incidence of clinically significant upper and/or lower GI events. The aim of the study is to determine the difference between Celebrex and combined therapy in the incidence of clinically significant upper and/or lower GI events. The patients, aged >/= 60, are with or without a history of gastroduodenal ulceration, or >/= 18 years with documented evidence of ulceration >/= 90 days prior to screening. * A total of 662 healthy subjects (mean age, 58 years) were randomized to Celebrex (200 mg qd) + aspirin (81mg qd), n=267; naproxen (500 mg bid) + aspirin (81 mg qd),n=264; placebo + aspirin (81 mg qd), n=131) for one week. There were no significant differences in baseline demographics between groups. Significantly more evaluable subjects randomized to naproxen (500 mg bid) + aspirin (81 mg qd) had endoscopic gastric and/or duodenal ulcers (65/257, 25.3%) compared with those receiving Celebrex (200 mg qd) + aspirin (81 mg qd) (18/257, 7%) or placebo (2/129, 1.6%, P<0.001 both comparisons) The incidence of endoscopic gastric and/or duodenal ulcers was higher in the Celebrex group vs. placebo (P=0.016) Significantly fewer Celebrex (200 mg qd) + aspirin (81 mg qd) treated subjects had endoscopic gastric or duodenal ulcers compared with naproxen (500 mg bid) + aspirin (81 mg qd) (gastric ulcers: 5.8% vs. 22.26%; duodenal ulcers: 1.2% vs. 7%; P<0.001 both comparisons). More Celebrex-treated subjects had endoscopic gastric ulcers vs. placebo (5.8% vs. 0.8%, P=0.016) but there was no significant difference in the incidence of endoscopic duodenal ulcers (1.2% vs. 0.8%, P=0.616). ** A total of 463 subjects (mean age, 57 years) were randomized to Celebrex (200 mg qd) + aspirin (325 mg qd), n=187; naproxen (500 mg bid) + aspirin (325 mg qd), n=182; placebo + aspirin (325 mg qd), n=94). A lower incidence of endoscopic gastric and duodenal ulcers was seen in Celebrex (200 mg qd) + aspirin (325 mg qd) group (18.7%) vs. naproxen (500 mg bid) + aspirin (325 mg qd) (27.3%; relative risk [RR]: 0.63,95% CI: 0.44-0.92). Both naproxen (500 mg bid) + aspirin (325 mg qd) and Celebrex (200 mg qd) + aspirin (325 mg qd) demonstrated a higher incidence of endoscopic gastric and duodenal ulcers vs. placebo + aspirin (325 mg qd) (7.6%; RR: 3.68. 95% CI: 1.79-7.60 and RR: 2.62, 95% CI: 1.19-5.78, respectively). *** Adherence with PPI was assessed based on the overlap in days between continuous ns-NSAID and PPI treatment episodes, including gaps < 30 days between consecutive prescriptions. Patients were considered adherent when the overlap between the treatment episode of ns-NSAID and PPI was >/=80%. REFERENCES: 1, Goldstein J, et al. Effects of concomitant aspirin (81mg qd) on incidence of gastric and/or duodenal ulcers in healthy subjects taking celecoxib or naproxen: a randomized, placebo-controlled trial. Presented at the European League Against Rheumatism (EULAR) Meeting, 21- 24 June, 2006. 2. Meade TW, Brennan PJ. Determination of who may derive most benefit from aspirin in primary prevention: subgroup results from a randomised controlled trial. BMJ 2000; 321: 13-7. 3. Sanmuganathan PS, Ghahramani P, Jackson PR, Wallis EJ, Ramsay LE. Aspirin for primary prevention of coronary heart disease: safety and absolute benefit related to coronary risk derived from meta-analysis of randomised trials. Heart 2001; 85: 265-71. 4. Patrono C, Garcia Rodriguez LA, Landolfi R, Baigent C. Low-dose aspirin for the prevention of atherothrombosis. N Engl J Med 2005; 353: 2373-83. 5. Laine L. Approaches to nonsteroidal anti-inflammatory drug use in the high-risk patient. Gastroenterology 2001; 120: 594-606. 6. Garcia Rodriguez LA, Jick H. Risk of upper gastrointestinal bleeding and perforation associated with individual nonsteroidal anti-inflammatory drugs. Lancet 1994; 343: 769-72. 7. Langman MJ, Weil J, Wainwright P, et al. Risks of bleeding peptic ulcer associated with individual non-steroidal anti-inflammatory drugs. Lancet 1994; 343: 1075-8. 8. Griffin MR, Piper JM, Daugherty JR, Snowden M, Ray WA. Nonsteroidal anti-inflammatory drug use and increased risk for peptic ulcer disease in elderly persons. Ann Intern Med 1991; 114: 257-63. 9. Goldstein J, et al. The impact of low-dose aspirin on endoscopic gastric and duodenal ulcer rates in users of a nonselective nonsteroidal anti-inflammatory drug or a cyclooxygenase-2-selective inhibitor. Aliment Pharmacol Ther 2006;15;23(10):1489-98. 10. Singh G, et al. Call to arms: Lack of gastroprotection is a new and increasing danger for elderly users of NSAIDs with arthritis. Presented at the European League Against Rheumatism (EULAR) Meeting, 21- 24 June, 2006. 11. Moore A, Derry S. Gastrointestinal harm from NSAIDS: An operations research approach. Presented at the European League Against Rheumatism (EULAR) Meeting, 21- 24 June, 2006. 12. van der Bij S, et al. Impact of proton pump inhibitor therapy and non-selective NSAID treatment adherence on gastrointestinal hospitalizations. Presented at the European League Against Rheumatism (EULAR) Meeting, 21- 24 June, 2006. SOURCE: Pfizer --------------------------------------------------------------------------------------------- Copyright © 1999 P\S\L Consulting Group Inc. All rights reserved. Republication or redistribution of P\S\L content is expressly prohibited without the prior written consent of P\S\L. 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