I Wilson

Characteristics of patients with irritable bowel syndrome recruited from three sources: implications for clinical trials

Variation in the characteristics of irritable bowel syndrome patients recruited for clinical trials from different sources could affect their response and the generalizability of trial results.

Influence of sex and Helicobacter pylori on development and healing of gastroduodenal lesions in non-steroidal anti-inflammatory drug users

Background and aims: Factors predisposing to endoscopic ulcer formation or healing with non-steroidal anti-inflammatory drugs (NSAIDs) have not been well defined. Methods: We used multivariate analysis of data from three large similar trials to identify factors associated with endoscopic lesions and healing. We compared the effectiveness of omeprazole 20 mg and 40 mg daily, misoprostol 200 μg four times daily, and ranitidine 150 mg twice daily in healing ulcers and erosions at different sites and in patients who were Helicobacter pylori positive and negative. Results: Older age, past ulcer history, rheumatoid arthritis, and H pylori infection were significantly associated with ulcers. Duodenal ulcer was significantly more likely than gastric ulcer with a past ulcer history (odds ratio 1.59, 1.16–2.17), H pylori infection (1.4, 1.04–1.92), and male sex (2.35, 1.75–3.16) while female sex, older age (≥60 years: 1.39, 1.03–1.88), and higher NSAID dose (>1 defined daily dose: 1.57, 1.16–2.14) were associated with gastric ulceration. Sex differences were seen in both H pylori positive and negative patients. Gastric and duodenal ulcer healing was significantly faster with omeprazole 20 mg than with misoprostol 200 μg four times daily or ranitidine 150 mg twice daily although misoprostol was more effective at healing erosions. Gastric ulcer healing was slower with large ulcers (0.37, 0.25–0.54 for >10 mm v 5–10 mm) or a past ulcer history (0.51, 0.34–0.76), and faster with H pylori infection (1.55, 1.06–2.29), especially with acid suppression (72% v 37% at four weeks with ranitidine). Conclusions: Among NSAID users, H pylori and male sex independently increase the likelihood of duodenal ulceration. H pylori infection does not affect duodenal ulcer healing and enhances gastric ulcer healing by ranitidine and possibly other acid suppressing treatments.

Relative contribution of mucosal injury and Helicobacter pylori in the development of gastroduodenal lesions in patients taking non-steroidal anti-inflammatory drugs

Background and aims: A past history of peptic ulceration increases the risk of an ulcer developing during non-steroidal anti-inflammatory drug (NSAID) use. Whether this is due to Helicobacter pylori infection or to reactivation of the original lesion is unclear. Methods: We used multivariate regression analyses of three large similar trials to identify factors that placed patients at high risk of ulcer development or relapse. We compared the efficacy of omeprazole 20 mg daily, misoprostol 200 μg twice daily, and ranitidine 150 mg twice daily in preventing ulcers and erosions at different sites and in patients who were H pylori positive and negative. Results: Patients with endoscopic lesions (which healed) initially were significantly more likely than those without to develop further erosions or ulcers during treatment (rate ratio 2.12, 1.07–4.17). Risk mounted further with ulcers versus erosions, particularly those that had been slow to heal. There was a highly significant tendency for the relapse lesion to replicate the site and type of the original lesion (mean odds ratios ranging from 3 to 14). Treatment failure was significantly less likely with omeprazole than with placebo, misoprostol, or ranitidine. This advantage was especially evident in H pylori positive patients receiving acid suppression (5.7% v 16.6% for gastric ulcer with omeprazole). Conclusions: Relapse of lesions in patients taking NSAIDs was highly site and type specific and not adversely affected by H pylori status. This strongly implies that local mucosal factors predispose to ulcer development in patients taking NSAIDs. Identification of the responsible mucosal changes would aid understanding and could promote better treatment.

Gastro-duodenal protection in an era of cyclo-oxygenase-2-selective nonsteroidal anti-inflammatory drugs.

 Nonsteroidal anti-inflammatory drugs (NSAIDs) relieve pain and inflammation, thereby improving quality of life in patients with arthritis. NSAIDs are associated with upper gastrointestinal side effects, such as bothersome upper gastrointestinal symptoms with a negative influence on quality of life; they are sometimes associated with potentially life-threatening gastro-duodenal ulceration. Cyclo-oxygenase-2 (COX-2)-selective NSAIDs are associated with a lower risk of ulceration than non-selective NSAIDs, but comparable proportions of NSAID users report upper gastrointestinal symptoms regardless of COX-2 selectivity. Co-administration of a COX-2-selective NSAID and low-dose aspirin carries the same risk of gastrointestinal complications as a non-selective NSAID given alone. A proton pump inhibitor (PPI) should be used for healing, and a PPI or misoprostol considered for prevention of ulceration associated with NSAID use. Nonsteroidal anti-inflammatory drugs (NSAIDs) are effective and necessary for the relief of pain and inflammation in patients with arthritis. NSAIDs are however also associated with an increased risk for ulceration in the stomach and in the duodenum, and many NSAID users experience bothersome dyspeptic symptoms during continued NSAID therapy. PPIs like omeprazole, have been shown to heal and to prevent ulcers and dyspeptic symptoms during continued NSAID therapy, and during continued NSAID therapy the prostaglandin analogue, misoprostol, has been shown to reduce the risk for ulcer complications. The COX-2 selective NSAID, rofecoxib, is in comparison with naproxen, a non-selective NSAID, associated with fewer clinically important upper gastrointestinal events. The incidence of myocardial infarctions seems, however, to be lower with naproxen than with rofecoxib, and this is expected to lead to low-dose aspirin use in rofecoxib users at risk for cardiovascular events. Co-administration of the COX-2 selective NSAID, celecoxib, and low-dose aspirin, is associated with the same risk for upper gastrointestinal ulcer complications alone and combined with symptomatic ulcers, as the non-selective NSAIDs, ibuprofen and diclofenac. A proton pump inhibitor (PPI) should be used for healing of NSAID-associated ulcers, and a PPI or misoprostol should be considered for prevention of ulceration in non-selective NSAID users at risk for ulceration. The experience with COX-2 selective NSAIDs is still limited, and it remains to be studied whether subpopulations of COX-2 selective NSAID users will benefit from gastro-duodenal protection.

Management of gastroduodenal ulcers and gastrointestinal symptoms associated with nonsteroidal anti-inflammatory drug therapy: A summary of four comparative trials with omeprazole, ranitidine, misoprostol, and placebo

Abstract Background: Nonsteroidal anti-inflammatory drugs (NSAIDs) are effective in the treatment of systemic diseases such as rheumatoid arthritis but are associated with a range of adverse gastrointestinal (GI) side effects, including dyspepsia, peptic ulcer, and ulcer complications. Several studies have compared the relative efficacy and tolerability of omeprazole, ranitidine, and misoprostol in the management of NSAID-associated GI adverse events. Objective: The purpose of this paper is to summarize and evaluate the results of 4 clinical studies that compared the efficacy and tolerability of omeprazole, misoprostol, and ranitidine in the acute and maintenance treatment of NSAID-associated gastroduodenal ulcers and GI symptoms. Methods: The 4 trials, which included 1822 patients being treated continuously with NSAIDs, studied omeprazole (20 and 40 mg once daily) as acute treatment for healing gastroduodenal ulcers and erosions and as prophylaxis (20 mg once daily) over 3 to 6 months. Comparators were misoprostol 200 μg 4 times daily or ranitidine 150 mg twice daily in the acute phases and misoprostol 200 μg twice daily, ranitidine 150 mg twice daily, or placebo in the prophylactic phases. Results: Gastric and duodenal ulcer healing rates were higher with omeprazole than with either misoprostol ( P = 0.004 for gastric ulcers; P P P = 0.032 for duodenal ulcers). A significantly larger percentage of patients taking misoprostol had the number of gastric or duodenal erosions reduced from >10 to P P = 0.008). More patients taking omeprazole remained in remission than patients taking misprostol ( P = 0.001), ranitidine ( P = 0.004), or placebo ( P Conclusions: Omeprazole was more effective in healing and prophylaxis of NSAID-associated gastroduodenal ulceration and symptoms than misoprostol and ranitidine in chronic NSAID users, and was better tolerated than misoprostol.

The site and size of previous gastroduodenal lesions predict the nature of relapse in NSAID-users on maintenance treatment

G1391 THE SITE AND SIZE OF PREVIOUS GASTRODUODENAL LESIONS PREDICT THE NATURE OF RELAPSE IN NSAID-USERS ON MAINTENANCE TREATMENT. ND Yeomans 1, AJ Swannell 2, G L~mgstrtim 3, ! Wilson 3, CJ Hawkey 4. IUniv. of Melbourne, Dept. of Medicine, Western Hospital, Melboume, Australia, 2Rheumatology Unit, City Hospital, Nottingham, UK, 3Astra Hassle AB, Mtilndal, Sweden, 4Div. Gastroenterology, University Hospital, Nottingham, UK.