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Editorial Analysis of the effect of COX-2 specific inhibitors and recommendations for their use in clinical practice. 2000
Lipsky PE, Abramson SB, Breedveld FC, Brook P, Burmester R, Buttgereit F, Cannon GW, Catella-Lawson F, Crofford LJ, Doherty M, Dougados M, DuBois RN, Froelich J, Garcia Rodriguez LA, Gibofsky A, Hernandez-Diaz S, Hochberg MC, Krause A, Liang MH, Machold K, Peloso PM, Raisz LG, Schayes B, Scheiman JM, Simon LS, Smolen J. · No affiliation provided · J Rheumatol. · Pubmed #10852251 No free full text.
This publication has no abstract.
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Review Practical approaches to minimizing gastrointestinal and cardiovascular safety concerns with COX-2 inhibitors and NSAIDs. 2005
Scheiman JM, Fendrick AM. · Division of Gastroenterology at the University of Michigan Medical Center, Ann Arbor, Michigan, USA. · Arthritis Res Ther. · Pubmed #16168078 No free full text.
Abstract: Nonsteroidal anti-inflammatory drugs (NSAIDs) are highly effective in treating the pain and inflammation associated with osteoarthritis and rheumatoid arthritis, but it is well recognized that these agents are associated with substantial gastrointestinal toxicity. Treatment guidelines suggest that patients with one or more risk factors for NSAID associated ulcers should be prescribed preventive treatment. However, well over 80% of such patients may not receive an appropriate therapeutic intervention. Multiple strategies are available to reduce the risk for NSAID associated gastrointestinal complications. First, risk may be reduced by using non-NSAID analgesics. Second, use of the minimum effective dose of the NSAID may reduce risk. Third, co-therapy with a proton pump inhibitor or misoprostol may be desirable in at-risk patients. Use of cyclo-oxygenase-2 inhibitors may also reduce the risk for gastrointestinal events, although this benefit is eliminated in patients who receive aspirin, and cyclo-oxygenase-2 inhibitors may increase cardiovascular adverse events. The optimal management of NSAID related gastrointestinal complications must be based on the individual patient's risk factors for gastrointestinal and cardiovascular disease, as well as on the efficacy and tolerability of both the NSAID and accompanying gastroprotective agent.
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Review Gastroduodenal safety of cyclooxygenase-2 inhibitors. 2003
Scheiman JM. · Division of Gastroenterology, Department of Internal Medicine, University of Michigan Medical School, Ann Arbor, MI 48109-0362, USA. · Curr Pharm Des. · Pubmed #14529400 No free full text.
Abstract: Cyclooxygenase-1 (COX-1) derived eicosanoids promote gastroprotective mucosal defenses and induce platelet aggregation. By sparing COX-1, COX-2 specific inhibitors provide effective anti-inflammatory and analgesic activity while substantially reducing the risk of peptic ulcer disease and GI bleeding compared to dual COX inhibitors (traditional NSAIDs). Clinical studies of the COX-2-selective inhibitors have demonstrated efficacy equivalent to nonselective NSAIDs with significantly lower rates of GI toxicity. The incidence of endoscopic ulcers in some studies with coxibs has approximated placebo. However, as the detection of endoscopic lesions is not always correlated with symptomatic ulcers and ulcer complications, outcome studies of GI safety were performed. The results of large outcome studies have evaluated rofecoxib and celecoxib in over 39,000 patients with osteoarthritis or rheumatoid arthritis. Results of these studies showed that patients taking a supratherapeutic dose of rofecoxib or celecoxib had significantly lower rates of GI-related adverse events than those taking a nonselective NSAID. The GI safety of coxibs for patients using low dose aspirin concomitantly with a coxib appears to be reduced, particularly with regard to ulcer complications. Such data provide support for the COX-2 hypothesis and demonstrate that coxibs provide effective treatment of pain and inflammation with a reduced risk of gastropathy.
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Review Gastrointestinal outcomes: evidence for risk reduction in patients using coxibs. free! 2002
Scheiman JM. · Division of Gastroenterology, University of Michigan Medical Center, Ann Arbor, USA. · Am J Manag Care. · Pubmed #12458821 links to free full text
Abstract: This paper examines the importance of clinically relevant gastrointestinal (GI) outcomes in patients using nonsteroidal anti-inflammatory drugs (NSAIDs) and the risk reduction for adverse GI events associated with cyclooxygenase (COX)-2-selective inhibitors. Four large outcomes trials are reviewed, 2 each with celecoxib and rofecoxib. The results of outcomes studies are consistent with randomized controlled trials and demonstrate that coxibs are associated with significant reductions in clinically relevant GI outcomes. The reductions are observed in patients without GI risk factors as well as in those at risk, suggesting that these drugs have the potential to improve outcomes for all patients requiring NSAIDs.
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Review Outcomes studies of the gastrointestinal safety of cyclooxygenase-2 inhibitors. free! 2002
Scheiman JM. · University of Michigan Medical School, Ann Arbor 48109-0362, USA. · Cleve Clin J Med. · Pubmed #12086292 links to free full text
Abstract: Short-term endoscopic studies of the highly selective cyclooxygenase-2 (COX-2) inhibitors (coxibs) rofecoxib and celecoxib have shown that these agents are well tolerated and have efficacy equivalent to nonselective nonsteroidal anti-inflammatory drugs (NSAIDs) with fewer adverse effects on the upper gastrointestinal (GI) tract. These studies are limited, however, as the detection of endoscopic lesions is not well correlated with symptomatic ulcers and ulcer complications. Outcomes studies of the GI safety are, therefore, essential to understanding how coxibs are likely to perform in a clinical practice setting. Four large outcomes studies (Vioxx Gastrointestinal Outcomes Research, VIGOR; Assessment of Difference Between Vioxx and Naproxen to Ascertain Gastrointestinal Tolerability and Effectiveness trial, ADVANTAGE; Celecoxib Long-term Arthritis Safety Study, CLASS; and the Successive Celecoxib Efficacy and Safety Studies, SUCCESS) examined the GI safety of rofecoxib and celecoxib in over 39,000 patients with osteoarthritis or rheumatoid arthritis. Results of these studies showed that patients taking a supratherapeutic dose of rofecoxib or celecoxib had significantly lower rates of GI-related adverse events than those taking a nonselective NSAID (naproxen, ibuprofen, or diclofenac). Reduced risk of upper GI events was seen in patients with multiple risk factors and in patients using low-dose aspirin and corticosteroids concomitantly with a coxib. Results of large outcomes studies provide support for the COX-2 hypothesis and demonstrate the long-term safety and tolerability of coxibs.
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Review The economic implications of cyclooxygenase-2-specific inhibitors. 2001
Peloso PM, Scheiman JM. · Division of Rheumatology, Department of Medicine, University of Saskatchewan, Saskatoon, Saskatchewan, Canada. · Am J Med. · Pubmed #11173051 No free full text.
Abstract: Rheumatoid arthritis and osteoarthritis are prevalent and costly conditions. A large proportion of the direct costs associated with these conditions relates to management of iatrogenic side effects. The cyclooxygenase (COX)-2-specific inhibitors lead to equivalent control of pain and disability compared with traditional NSAIDs. However, the COX-2-specific inhibitors have significant potential to reduce health-care costs, principally through the reduction of side effects. These cost savings are most likely to be realized through reductions in costs associated with dyspepsia and upper gastrointestinal ulcers and bleeding. Reduced indirect costs through improved disability scores and improved health-related quality of life are also predictable with the use of COX-2-specific inhibitors. This is accomplished without the attendant increase in risk to the gastrointestinal tract associated with traditional NSAIDs.
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Article Prevention of ulcers by esomeprazole in at-risk patients using non-selective NSAIDs and COX-2 inhibitors. 2006
Scheiman JM, Yeomans ND, Talley NJ, Vakil N, Chan FK, Tulassay Z, Rainoldi JL, Szczepanski L, Ung KA, Kleczkowski D, Ahlbom H, Naesdal J, Hawkey C. · Division of Gastroenterology, Department of Internal Medicine, University of Michigan, Ann Arbor, Michigan 48109, USA. · Am J Gastroenterol. · Pubmed #16494585 No free full text.
Abstract: OBJECTIVES: Proton pump inhibitors reduce ulcer recurrence in non-steroidal anti-inflammatory drug (NSAID) users, but their impact in at-risk ulcer-free patients using the current spectrum of prescribed agents has not been clearly defined. We assessed esomeprazole for ulcer prevention in at-risk patients (> or = 60 yr and/or ulcer history) taking NSAIDs, including COX-2 inhibitors. Such studies are particularly relevant, given that concerns regarding adverse cardiovascular outcomes among COX-2 inhibitor users may prompt re-evaluation of their use. METHODS: We conducted two similar double-blind, placebo-controlled, randomized, multicenter studies; VENUS (United States) and PLUTO (multinational). A total of 844 and 585 patients requiring daily NSAIDs, including COX-2 inhibitors were randomized to receive esomeprazole (20 or 40 mg) or placebo, daily for 6 months. RESULTS: In the VENUS study, the life table estimated proportion of patients who developed ulcers over 6 months (primary variable, intent-to-treat population) was 20.4% on placebo, 5.3% on esomeprazole 20 mg (p < 0.001), and 4.7% on esomeprazole 40 mg (p < 0.0001). In the PLUTO study, the values were 12.3% on placebo, 5.2% with esomeprazole 20 mg (p = 0.018), and 4.4% with esomeprazole 40 mg (p = 0.007). Significant reductions were observed for users of both non-selective NSAIDs and COX-2 inhibitors. Pooled ulcer rates for patients using COX-2 inhibitors (n = 400) were 16.5% on placebo, 0.9% on esomeprazole 20 mg (p < 0.001) and 4.1% on esomeprazole 40 mg (p= 0.002). Esomeprazole was well tolerated and associated with better symptom control than placebo. CONCLUSIONS: For at-risk patients, esomeprazole was effective in preventing ulcers in long-term users of NSAIDs, including COX-2 inhibitors.
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