Association of upper gastrointestinal symptoms with gastroduodenal ulcers in endoscopic trials of arthritis patients treated with naproxen, celecoxib or placebo

A250 AGA ABSTRACTS

GASTROENTEROLOGY Vol. 118, No.4

1454

1456

ASSOCIATION OF UPPER GASTROINTESTINAL SYMPTOMS WITH GASTRODUODENAL ULCERS IN ENDOSCOPIC TRIALS OF ARTHRITIS PATIENTS TREATED WITH NAPROXEN, CELECOXIB OR PLACEBO. Jay L. Goldstein, Jeffery D. Kent, Clement 1. Maurath, Kenneth M. Verburg, G. Steven Geis, Univ of Illinois at Chicago, Chicago, IL; Searle Clin Research & Development, Skokie, IL. BACKGROUND: NSAIDs are associated with a high incidence of both upper gastrointestinal (UGI) symptoms and gastroduodenal ulcers (GDUs). However, the correlation of UGI symptoms with GDUs is poor and many GDUs occur in the absence of UGI symptoms. We examined the association of reported UGI symptoms (dyspepsia, nausea and abdominal pain) with GDUs found by scheduled endoscopy in arthritis patients treated with the COX-2 specific inhibitor celecoxib to that of naproxen 500 mg BID or placebo. METHODS: Data were pooled from two identical double-blind 12-week endoscopic trials in osteoarthritis and rheumatoid arthritis patients. Only patients free of GDUs at baseline were studied. Ulcers were defined as ~3mm diameter with depth. UGI symptoms were self-reported. RESULTS: The table shows the proportion of patients with UGI symptoms, GDU, or both. The percentage of patients who had a GDU who also had UGI symptoms were 22.2% (2/9 patients), 34.8% (15/43), and 35.2% (25171) for placebo, celecoxib, and naproxen, respectively. The percentage of patients with UGI symptoms who were found to have a GDU (positive predictive value) was 3.2% (2/63 patients) with placebo, 8.5% (15/176) with celecoxib and 27.2% (25/92) for naproxen. Similar analyses of gastric ulcers alone or using only UGI symptoms that occurred within 4 weeks of endoscopy yielded similar results. CONCLUSIONS: Celecoxib was associated with significantly fewer UGI symptoms and GDUs than naproxen and was similar to placebo. Irrespective of treatment, about one-third of endoscopic ulcers were associated with UGI symptoms. The positive predictive value of UGI symptoms for a GDU in both placebo- and celecoxib-treated patients was poor due to the low incidence of ulcers in these treatment groups. UGI symptoms were a weak predictor of a GDU in naproxen-treated patients; less than 30% of patients with UGI symptoms also had a GDU.

PRIMARY PROPHYLAXIS OF NSAID·INDUCED GASTRODUODENAL ULCERS AND DYSPEPSIA IN H. PYWRI (HP)-POSITIVE PATIENTS: RANDOMIZED, DOUBLE·BLIND, PLACEBO-CONTROLLED TREATMENT OF HP INFECTION VS. OMEPRAZOLE. Hans R. Koelz, Wolfgang Bolten, Brigitte Dragosics, Joachim Labenz, Wolfgang Roesch, Manfred Stolte, Andre L. Blum, Dept of Medicine, Triernli Hosp, Zurich, Switzerland; Rheumaklinik Wiesbaden II, Wiesbaden, Germany; Gesundheitszentrum Sued, Vienna, Austria; Evang JungStilling Krankenhaus, Siegen, Germany; Med Clin Krankenhaus Nordwest, Frankfurt, Germany; Inst f Pathology, Clin Bayreuth, Bayreuth, Germany; CHUV, Lausanne, Switzerland.

N UGlsymptoms GDU GDU + UGI symptoms

Placebo

Celecoxib (100-400 mgBID)

Naproxen

408 63(15.4%) 9(2.2%) 2(0.5%)

1044 176 (16.9%) 43(4.1%) 15(1.4%)

349 92(26.4%) 71 (20.3%) 25(7.2%)

1455 AN ENDOSCOPIC STUDY OF THE GASTRODUODENAL EFFECTS OF SC·69124A, A PARENTERAL COX·2·SPECIFIC INHffiITOR, IN THE ELDERLY. Richard C. HUbbard, Michael E. Kuss, Diane L. LeComte, Xiaorang Pan, Sheela Talwalker, G. Steven Geis, Searle Clin Research & Development, Skokie,lL. SC-69124A (parecoxib) is a parenteral anti-inflammatory analgesic agent that specifically inhibits the inducible isoform of the enzyme cyclooxygenase (COX-2). This double-blind, randomized endoscopic study compared the effects of SC-69I 24A with those ofketorolac and placebo on the upper gastrointestinal (UGI) mucosa in healthy elderly subjects. Ninety-four (94) healthy subjects aged 65 to 75 years with endoscopically proven normal UGI mucosa were randomized to receive SC-69124A 40 mg BID intravenously (n=3I), ketorolac 15 mg QID intravenously (n=31), or placebo (n = 32) for 7 days. (Ketorolac subjects received placebo for the first 2 days.) On Day 8, subjects underwent UGI endoscopy. Gastric and duodenal mucosae were examined separately, and results were compared using the Cochran-Mantel-Haenszel test. None of the differences between SC-69124A and placebo was statistically significant. The incidence of gastric ulcers was statistically significantly higher for ketorolac than for either SC-69124A or placebo. No duodenal ulcers occurred in either the SC-69124A or the placebo group. The incidences of erosions/ulcers were significantly higher for ketorolac than for either placebo or SC-69124A, in both the stomach and duodenum. SC-69124A was safe and well tolerated. In this study, the UGI mucosal effects of SC-69124A at its full therapeutic dose of 40 mg BID in elderly subjects over 7 days were generally similar to those of placebo. Ketorolac, at the low therapeutic dose of 15 mg QID, produced significant UGI damage after 5 days. Placebo Ulcer Incidence Gastroduodenal Gall1rfc Duodenal Erosion I Ulcer Incidence Gastric Duodenal

SC·69124A 40mg BID Ketorolac 15mg010

0(0%) 0(0%) 0(0%)

0(0%) 0(0%) 0(0%)

7(23%)' 5(16%)' 2(6%)

2(6%) 0(0%)

4(14%) 3(10%)

28(90%)' 14(45%)'

, P<0.05 vs SG-69124A and placebo.

Background and aim: The role of H. pylori in the development of NSAIDinduced gastropathy is not clear because correctly randomized, doubleblind studies are lacking. Methods: This trial was carried out in Germany, Austria and the Czech Republic. Included were patients with rheumatic disorders requiring NSAID treatment for at least 5 weeks and positive tests for HP (serology, rapid urease test and gastric histology). Excluded were patients already on NSAID treatment, with past or present peptic ulcers, and with therapy-requiring dyspepsia. Gastroscopy (with biopsies) was repeated after 5 weeks. NSAID treatment consisted of diclofenac 50 mg b.i.d. (increased to 50 mg t.i.d, plus tramadol up to 100 mg b.i.d. as needed). Randomly assigned treatment was omeprazole 20 mg o.d. for 5 weeks (0-0); omeprazole 20 mg b.i.d. plus amoxicillin 1000 mg plus clarithromycin 500 mg b.i.d. for I week, followed by placebo for 4 weeks (OAC-P); OAC for I week followed by omeprazole 20 mg for 4 weeks (OAC-O); or placebo for 5 weeks (P-P). The main outcome criterion was the incidence of ulcers (~3 rom). Results: Of 2264 patients screened, 732 were randomized and evaluated. Ulcers were observed in 14 patients (9 DU and 5 GU)(table). No ulcer complications were seen. All ulcers in the poP group occurred in patients with persisting HP whereas all ulcers after/ during active treatment were HP-ve. Therapy-requiring dyspepsia was less frequent in patients with active treatment. Conclusions: OAC treatment of HP alone protects against ulcers and dyspepsia during NSAID treatment. Co-therapy with omeprazole does not further improve the effect. Treatment of HP infection is a valid alternative to omeprazole prophylaxis.

Treatment (n) (a)Ulcer (b)>10 Erosions (e)Dyspepsiat Hawkey crlteriont

OAC·P(l79)

OAC·0(191)

0·0(173)

p.p (189)

2'(1%) 0 23' (13%) 25"(14%)

2'(1%) 1 (1%) 27' (14%) 28' (15%)

0" 3(2%) 25'(14%) 26'(15%)

10(5%) 4(2%) 43(23%) 50(26%)

vs. placebc: ' p
1457 ERADICATION OF HELICOBACTER PYLORI COULD NOT PREVENT DEVELOPMENT OF GASTROINTESTINAL COMPLI· CATIONS IN PATIENTS REQUIRING LONG-TERM LOW·DOSE ASPIRIN. Kam-Chuen Lai, Shiu-Kum Lam, Wai-Mo Hui, Chun-Yu Wong, Wayne Hu, Wai-Man Wong, On-On Chan, Man-Fung Yuen, Univ of Hong Kong, Hong Kong, P. R. China. Background: Eradication of H. pylori has been shown to reduce development of endoscopic gastroduodenal ulcers in patients newly started on NSAIDs. Aim: We aimed to study whether eradication of H. pylori could reduce long-term upper gastrointestinal complications of patients started on low-dose aspirin. Methods: Patients that required low-dose aspirin ~rophy­ laxis were recruited. Infection with H. pylori was determined by I C-urea breath test. Patients infected with H. pylori were given aspirin 100 mg daily and randomised to receive either (a) eradication therapy with omeprazole 20 mg, clarithromycin 500 mg and amoxycillin 1 gm 2x/day for 1 week Gp A or (b) no eradication treatment - Gp B. Patients without H. pylori infection were given aspirin 100 mg daily only - Group C. Patients were followed up regularly for the development of GI complications (including nonulcer dyspepsia-NUD, painful ulcer, ulcer bleeding and ulcer perforation) while aspirin was continued without maintenance therapy in all 3 groups. Results: 115 patients had finished at least 6 months follow-up. Seven patients that were non-compliant to the protocol were excluded from analysis. See table. Conclusion: (l) Low rates of serious upper gastrointestinal complications were seen in all 3 groups (2) Anti-helicobacter