J L Goldstein

Publications (24)130.92 Total impact

• Article: Risk factors associated with a decrease ≥2 g/dL in haemoglobin and/or ≥10% haematocrit in osteoarthritis patients taking celecoxib or a nonselective NSAID plus a PPI in a large randomised controlled trial (CONDOR).

  A Lanas, J L Goldstein, F K L Chan, C M Wilcox, D A Peura, C Li, G H Sands, J M Scheiman
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  ABSTRACT: Nonsteroidal anti-inflammatory drugs are associated with gastrointestinal (GI) damage. The Celecoxib vs. Omeprazole and Diclofenac for At-Risk Osteoarthritis and Rheumatoid Arthritis Patients (CONDOR) trial showed that a haemoglobin drop ≥2 g/dL adjudicated as either of defined or presumed GI origin was the most frequent component/event for the composite GI primary end point. This adverse event is potentially clinically relevant in long-term NSAID treatment. To define potential risk factors associated with a decrease in haemoglobin/haematocrit. Post hoc analysis of the CONDOR trial was conducted in the intention-to-treat population. Clinically significant blood loss was defined as: (i) a haemoglobin drop ≥2 g/dL and/or a haematocrit drop ≥10%; and (ii) blood loss adjudicated as either of defined or presumed GI origin. Fifteen risk factors were evaluated by stepwise logistic regression. Each factor had to be significant at <0.20 α to be included in the model. A total of 64/3774 (1.7%) osteoarthritis (OA) patients had decreased haemoglobin/haematocrit and were adjudicated to the GI endpoint. Significant risk factors, at the 0.20 α level found to be associated with clinically significant blood loss in OA patients included [odds ratio (80% CI)] baseline C-reactive protein (CRP) levels [2.27 (1.46-3.53)], history of gastritis and history of GI intolerance [1.55 (1.06-2.28)], positive Helicobacter pylori at screening [1.54 (1.07-2.22)], increasing age [1.17 (1.04-1.32)] and body mass index [BMI; 1.03 (1.00-1.06)]. Monitoring for decreases in haemoglobin should be considered for all OA patients and especially those with an increased age, BMI, history of gastritis and GI intolerance, CRP levels >1 mg/dL and/or positive H. pylori status, as this may affect their clinical management.
  Alimentary Pharmacology & Therapeutics 07/2012; 36(5):485-92. · 3.77 Impact Factor
• Source

  Available from: PubMed Central

  Article: Haemoglobin decreases in NSAID users over time: an analysis of two large outcome trials.

  J L Goldstein, F K L Chan, A Lanas, C M Wilcox, D Peura, G H Sands, M F Berger, H Nguyen, J M Scheiman
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  ABSTRACT: Nonsteroidal anti-inflammatory drugs (NSAIDs) have been associated with clinically significant decreases in haemoglobin dependent and independent of acute bleeding events. To evaluate the incidence and time to a clinically meaningful decrease in haemoglobin in two double-blind, prospective randomised clinical trials comparing NSAIDs in patients with osteoarthritis (OA) or rheumatoid arthritis (RA). In CLASS, patients with OA/RA who were aged ≥ 18 years and required continuous NSAID treatment were included; patients who were Helicobacter pylori positive and/or using aspirin were not excluded. In contrast, in the CONDOR trial, comparing celecoxib alone to diclofenac sustained release (plus omeprazole), patients were aged ≥ 60 years or ≥ 18 years with a history of gastroduodenal ulcer and were H. pylori negative; aspirin or other anti-platelet users were excluded. To make a parallel post hoc analysis we limited our study to 6 months and the populations to only the non-aspirin users in CLASS and those patients receiving either celecoxib or diclofenac. A decrease in haemoglobin of ≥ 2 g/dL defined the primary end point. At 6 months, in the CLASS and CONDOR trials, 1.9% and 2.0% of patients treated with celecoxib and 3.3% and 5.7% of patients treated with diclofenac developed a ≥ 2 g/dL decrease in haemoglobin, respectively, [CLASS: odds ratio (OR) 1.80 (95% confidence interval (CI), 1.22-2.65) and CONDOR: OR 2.93 (95% CI, 2.06-4.15), respectively]. IN these two large, independent trials, clinically-meaningful decreases in haemoglobin ≥ 2 g/dL occurred in a relatively similar fashion over time despite differences in trial designs.
  Alimentary Pharmacology & Therapeutics 08/2011; 34(7):808-16. · 3.77 Impact Factor
• Article: Clinical trial: endoscopic evaluation of naproxen etemesil, a naproxen prodrug, vs. naproxen - a proof-of-concept, randomized, double-blind, active-comparator study.

  J L Goldstein, A Jungwirthová, J David, E Spindel, L Bouchner, F Pešek, S Searle, J Skopek, J Grim, I Ulč, K L Sewell
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  ABSTRACT: Nonsteroidal anti-inflammatory drugs are associated with upper gastrointestinal mucosal injury. Naproxen etemesil is a lipophilic, non-acidic, inactive prodrug of naproxen that is hydrolysed to pharmacologically active naproxen once absorbed. We hypothesized that with lesser topical exposure to naproxen from the prodrug, there would be reduced gastroduodenal mucosal injury compared with naproxen. To compare the degree of endoscopic mucosal damage of naproxen etemesil vs. naproxen. This multicentre, randomized, double-blind, double-dummy trial compared oral naproxen etemesil 1200 mg twice daily (n = 61) with naproxen 500 mg twice daily (n = 59) for 7.5 days in 120 healthy subjects (45-70 years; mean 51 years; 58% female) with baseline total modified gastroduodenal Lanza score ≤ 2 (no erosions/ulcers) on endoscopy. The primary endpoint was mean total modified gastroduodenal Lanza score on day 7. A secondary endpoint was incidence of gastric ulcers. The day 7 mean total modified gastroduodenal Lanza score was 2.8 ± 1.7 for naproxen etemesil vs. 3.5 ± 2.0 for naproxen (P = 0.03), and significantly fewer naproxen etemesil-treated subjects (3.3%) developed gastric ulcers compared with naproxen-treated subjects (15.8%) (P = 0.02). In this first proof-of-concept study, naproxen etemesil was associated with significantly lower gastroduodenal mucosal injury compared with naproxen after 7 days of exposure (Clinical trial number: NCT00750243).
  Alimentary Pharmacology & Therapeutics 11/2010; 32(9):1091-101. · 3.77 Impact Factor
• Article: Clinical trial: the incidence of NSAID-associated endoscopic gastric ulcers in patients treated with PN 400 (naproxen plus esomeprazole magnesium) vs. enteric-coated naproxen alone.

  J L Goldstein, M C Hochberg, J G Fort, Y Zhang, C Hwang, M Sostek
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  ABSTRACT: Gastroprotective co-therapy may reduce the risk of nonsteroidal anti-inflammatory drug (NSAID)-associated gastric ulcers, but adherence is suboptimal. To compare the incidence of gastric ulcers with PN 400 [enteric-coated (EC) naproxen 500 mg and immediate-release esomeprazole 20 mg], or EC naproxen. Two randomized, double-blind, multicentre studies (PN400-301, PN400-302). Patients [stratified by low-dose aspirin (< or =325 mg) use] aged > or =50 years or 18-49 years with a history of ulcer, received PN 400 BID (301, n = 218; 302, n = 210) or EC naproxen 500 mg BID (301, n = 216; 302, n = 210) for 6 months. The primary endpoint was the cumulative incidence of endoscopic gastric ulcers. The cumulative incidence of gastric ulcers was significantly lower with PN 400 vs. EC naproxen (301: 4.1% vs. 23.1%, P < 0.001; 302: 7.1% vs. 24.3%, P < 0.001). PN 400 was associated with a lower combined incidence of gastric ulcers vs. EC naproxen in low-dose aspirin users (n = 201) (3.0% vs. 28.4%, P < 0.001) and non-users (n = 653) (6.4% vs. 22.2%, P < 0.001). The incidence of, and discontinuations due to, upper gastrointestinal (UGI) AEs was significantly lower with PN 400 relative to EC naproxen (P < 0.01, both studies). PN 400 significantly reduces the incidence of gastric ulcers, regardless of low-dose aspirin use, in at-risk patients, and is associated with improved UGI tolerability relative to EC naproxen (ClinicalTrials.gov, NCT00527782).
  Alimentary Pharmacology & Therapeutics 05/2010; 32(3):401-13. · 3.77 Impact Factor
• Article: Clinical trial: healing of NSAID-associated gastric ulcers in patients continuing NSAID therapy - a randomized study comparing ranitidine with esomeprazole.

  J L Goldstein, J F Johanson, C J Hawkey, L J Suchower, K A Brown
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  ABSTRACT: The use of non-steroidal anti-inflammatory drugs (NSAID) is associated with an increased risk of gastric ulcer (GU) development. This multicentre, randomized, double-blind, parallel-group trial compared endoscopic healing rates at 4 and 8 weeks after treatment with oral esomeprazole 40 or 20 mg once daily, or ranitidine 150 mg twice daily, in patients with 1 baseline GU > or = 5 mm but no GUs or duodenal ulcers >25 mm in diameter who received continued cyclooxygenase-2-selective or non-selective NSAID therapies. The primary outcome was the percentage of patients in each treatment group who had no GUs at week 8. Four hundred and forty patients were randomized to treatment. At week 8, GU healing rates (95% CI) with esomeprazole 40 mg, esomeprazole 20 mg and ranitidine were 85.7 (79.8-91.7)%, 84.8 (78.8-90.8)% and 76.3 (69.2-83.3)%, respectively; between-group differences were not statistically significant. Week-4 GU healing rates were 70.7 (62.9-78.4)% and 72.5 (65.0-79.9)% with esomeprazole 40 and 20 mg, respectively, and were significantly higher (P < 0.01 for both doses) than those with ranitidine [55.4 (47.1-63.7)%]. In patients who require continued NSAID therapy, GU healing rates at 8 weeks numerically favoured esomeprazole but were not significantly different from ranitidine.
  Alimentary Pharmacology & Therapeutics 10/2007; 26(8):1101-11. · 3.77 Impact Factor
• Article: Small bowel mucosal injury is reduced in healthy subjects treated with celecoxib compared with ibuprofen plus omeprazole, as assessed by video capsule endoscopy.

  J L Goldstein, G M Eisen, B Lewis, I M Gralnek, J Aisenberg, P Bhadra, M F Berger
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  ABSTRACT: Small bowel mucosal injury associated with non-selective non-steroidal anti-inflammatory drugs is being increasingly recognized. To evaluate the incidence of small bowel injury in healthy subjects receiving celecoxib or ibuprofen plus omeprazole using video capsule endoscopy (VCE). Subjects with normal baseline VCE were randomly assigned to receive celecoxib 200 mg b.d., ibuprofen 800 mg t.d.s. plus omeprazole 20 mg o.d. or placebo for 2 weeks. The primary end point was mean number of small bowel mucosal breaks per subject. Secondary end points included correlation of faecal calprotectin levels with the primary outcome. After treatment, the mean number of small bowel mucosal breaks per subject and the percentage of subjects with mucosal breaks were 0.7/25.9% for ibuprofen/omeprazole compared with 0.2/6.4% for celecoxib and 0.1/7.1% placebo (both comparisons P < 0.001). There were no significant differences between celecoxib and placebo in any measure. Mean increases in faecal calprotectin levels were higher in subjects receiving ibuprofen/omeprazole compared with celecoxib (P < 0.001), but no correlation was determined between these levels and small bowel mucosal breaks. Among healthy subjects with no baseline endoscopic lesions, celecoxib was associated with significantly fewer small bowel mucosal breaks than ibuprofen/omeprazole as assessed by VCE.
  Alimentary Pharmacology & Therapeutics 05/2007; 25(10):1211-22. · 3.77 Impact Factor
• Article: Effects of Concomitant Aspirin (81 Mg Qd) on Incidence of Gastric and/or Duodenal Ulcers in Healthy Subjects Taking Celecoxib or Naproxen: A Randomized, Placebo-Controlled Trial: 58

  J L. Goldstein, J Aisenberg, M Berger, W E. Dodge
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  ABSTRACT: An abstract is unavailable. This article is available as HTML full text and PDF.
  JCR Journal of Clinical Rheumatology 07/2006; 12(4):S18. · 1.36 Impact Factor
• Article: The impact of low-dose aspirin on endoscopic gastric and duodenal ulcer rates in users of a non-selective non-steroidal anti-inflammatory drug or a cyclo-oxygenase-2-selective inhibitor.

  J L Goldstein, S C Lowry, F L Lanza, H I Schwartz, W E Dodge
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  ABSTRACT: The effect of low-dose aspirin on endoscopic ulcer incidence in cyclo-oxygenase-2-selective inhibitor or non-selective non-steroidal anti-inflammatory drug users remains controversial. To compare prospectively the incidence of endoscopic ulcers in healthy subjects receiving low-dose aspirin plus celecoxib or naproxen. In this double-blind, placebo-controlled, 1-week study, subjects (50-75 years) were randomized to receive aspirin 325 mg o.d. plus either celecoxib 200 mg o.d., naproxen 500 mg b.d., or placebo. Baseline and end of study endoscopies were performed. The primary end point was incidence of one or more gastric and duodenal ulcers. A lower incidence of gastric and duodenal ulcers was seen in celecoxib/aspirin-treated subjects (19%) vs. naproxen/aspirin (27%; RR: 0.63, 95% CI: 0.44-0.92). Both naproxen/aspirin and celecoxib/aspirin groups demonstrated a higher incidence of gastric and duodenal ulcers vs. placebo/aspirin (8%; RR: 3.7, 95% CI: 1.8-7.6 and RR: 2.6, 95% CI: 1.2-5.8, respectively). Fewer endoscopic ulcers were observed in patients treated with celecoxib/aspirin vs. naproxen/aspirin. However, celecoxib/aspirin was associated with a significantly higher incidence of gastric and duodenal ulcers than aspirin alone. Further studies are required to determine the generalizability of these findings in the aspirin users and to determine the appropriate strategy to minimize risk in susceptible patients.
  Alimentary Pharmacology & Therapeutics 06/2006; 23(10):1489-98. · 3.77 Impact Factor
• Article: Meta-analysis: upper gastrointestinal tolerability of valdecoxib, a cyclooxygenase-2-specific inhibitor, compared with nonspecific nonsteroidal anti-inflammatory drugs among patients with osteoarthritis and rheumatoid arthritis.

  G M Eisen, J L Goldstein, D B Hanna, D A Rublee
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  ABSTRACT: To compare the incidence of abdominal pain, dyspepsia and/or nausea associated with valdecoxib, nonspecific nonsteroidal anti-inflammatory drugs and placebo in patients with rheumatoid arthritis and osteoarthritis. Data from five randomized, double-blind 12-week trials were pooled. Independent risk factors for abdominal pain, dyspepsia and/or nausea were also determined. The final analysis consisted of 4394 patients. Nonspecific nonsteroidal anti-inflammatory drug users (n = 1185) received naproxen 1000 mg/day (n = 766), ibuprofen 2400 mg/day (n = 207) or diclofenac sodium 150 mg/day (n = 212). Valdecoxib users received 10 mg/day (n = 955), 20 mg/day (n = 851) or 40 mg/day (n = 430). A total of 973 patients received placebo. The nonspecific nonsteroidal anti-inflammatory drug group was most likely to report abdominal pain or dyspepsia, while the placebo group reported the highest incidence of nausea. The most important risk factors for abdominal pain, dyspepsia and/or nausea were nonspecific nonsteroidal anti-inflammatory drug use, gastrointestinal history of nonspecific nonsteroidal anti-inflammatory drug-related intolerance or gastroduodenal ulcers, osteoarthritis diagnosis, female gender and age <65 years. This pooled analysis demonstrates a clear decrease in dyspepsia and an improvement in upper gastrointestinal tolerability for patients with osteoarthritis and rheumatoid arthritis taking valdecoxib, even at supratherapeutic doses, compared with those taking nonspecific nonsteroidal anti-inflammatory drugs over 12 weeks.
  Alimentary Pharmacology & Therapeutics 04/2005; 21(5):591-8. · 3.77 Impact Factor
• Article: Reduced incidence of upper gastrointestinal ulcer complications with the COX-2 selective inhibitor, valdecoxib.

  J L Goldstein, G M Eisen, N Agrawal, W F Stenson, J D Kent, K M Verburg
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  ABSTRACT: In a predefined analysis, data were pooled from eight blinded, randomized, controlled trials, and separately from three long-term, open-label trials to determine the rate of upper gastrointestinal ulcer complications with the cyclo-oxygenase-2 selective inhibitor, valdecoxib, vs. non-selective non-steroidal anti-inflammatory drugs. In randomized, controlled trials, 7434 osteoarthritis and rheumatoid arthritis patients received placebo (n = 973), valdecoxib 5-80 mg daily (n = 4362), or a non-selective non-steroidal anti-inflammatory drug (naproxen, ibuprofen or diclofenac; n = 2099) for 12-26 weeks. In long-term, open-label trials, 2871 patients received valdecoxib 10-80 mg daily for up to 1 year. All potential events were reviewed by a blinded, independent review committee based on a priori definitions of ulcer complications (perforations, obstructions, bleeds). In randomized, controlled trials, 19 of 955 potential events were adjudicated to be ulcer complications. Valdecoxib was associated with a significantly lower ulcer complication rate than non-selective non-steroidal anti-inflammatory drugs (0.68% vs. 1.96%, all patients; 0.29% vs. 2.08%, non-aspirin users; P < 0.05). In long-term, open-label trials, seven of 310 potential events were adjudicated to be ulcer complications; the annualized incidence for valdecoxib was 0.39% (seven of 1791 patient-years) for all patients and 0.2% (three of 1472 patient-years) for non-aspirin users. Valdecoxib, including above recommended doses, is associated with a significantly lower rate of upper gastrointestinal ulcer complications than therapeutic doses of non-selective non-steroidal anti-inflammatory drugs.
  Alimentary Pharmacology & Therapeutics 10/2004; 20(5):527-38. · 3.77 Impact Factor
• Article: Application of a propensity score to adjust for channelling bias with NSAIDs.

  S V Morant, D Pettitt, T M MacDonald, T A Burke, J L Goldstein
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  ABSTRACT: To compare the relative risks of upper GI haemorrhage (UGIH) in users of Newer versus Older, non-specific NSAIDs when adjusted for channelling bias by regression on individual covariates, a propensity score and both. Cohort study of patients prescribed NSAIDs between June 1987 and January 2000. Exposure to Newer and Older non-specific NSAIDs was identified, and risk factors evaluated for each patient. Results of multiple covariate analyses and the propensity scoring technique to assess potential channelling bias in comparisons between Newer and Older non-specific NSAIDs were compared. This study included 7.1 thousand patient years (tpy) exposure to meloxicam, 1.6 tpy exposure to coxibs, and 628 tpy exposure to Older non-specific NSAIDs. Patients receiving Newer NSAIDs were older, more likely to have a history of GI symptoms, and at higher risk for GI complications. Adjusting for these risk factors reduced the relative risks of UGIH on meloxicam and coxibs versus Older non-specific NSAIDs to 0.84 (95%CI 0.60, 1.17) and 0.36 (0.14, 0.97) respectively. Channelling towards high GI risk patients occurred in the prescribing of Newer NSAIDs. Propensity scores highlighted the markedly different risk profiles of users of Newer and Older non-specific NSAID. Correcting for channelling bias, coxib exposure, but not meloxicam exposure, was associated with less UGIH than Older non-specific NSAID exposure. In the present study, corrections made by regression on a propensity score and on individual covariates were similar.
  Pharmacoepidemiology and Drug Safety 07/2004; 13(6):345-53. · 2.53 Impact Factor
• Article: Adherence to proton pump inhibitors or H2-receptor antagonists during the use of non-steroidal anti-inflammatory drugs.

  M C J M Sturkenboom, T A Burke, M J D Tangelder, J P Dieleman, S Walton, J L Goldstein
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  ABSTRACT: The efficacy of proton pump inhibitors (PPIs) or histamine-2 receptor antagonists (H2RAs) prescribed as prophylaxis for NSAID-related upper gastrointestinal (UGI) toxicity is dependent upon patient adherence. To describe patient adherence to prophylactically prescribed PPIs and H2RAs in the clinical setting. We conducted a retrospective observational cohort study using the Integrated Primary Care Information Project database. The study population consisted of incident non-specific NSAID users prescribed a PPI or H2RA specifically as prophylaxis for NSAID-related UGI toxicity. Patients were classified as non-adherent if < 75% of days of NSAID use were covered by one of these agents, and as continuing users after discontinuation of NSAID use if they had a renewed prescription for these agents after their last NSAID prescription. The study cohort comprised 784 patients: 374 with H2RAs, 405 with PPIs, and 5 with both PPI and H2RA. Eighty-five percent of H2RA users and 7% of PPI users were prescribed these drugs at doses below the minimum recommended/effective dose for NSAID-associated gastroduodenal ulcer prophylaxis. Thirty-seven percent of patients were non-adherent. The lowest rate of non-adherence was associated with the first NSAID prescription (9%), increasing to 61% for patients with >/= 3 prescriptions. In a cohort of subjects who stopped their NSAID and were followed for up to 2 years (n = 711), there was significant persistent use of acid suppressive agents; 40% of patients had at least one additional prescription for the acid suppressive agent after stopping NSAIDs, and> 30% received enough drug to cover a period longer than 2 months after stopping their NSAID. The pattern of PPI and H2RA prescriptions, when prescribed as prophylactic strategy, does not correspond with the pattern of NSAID use. Physicians should consider the medical impact of non-adherence with dual therapies and the impact of prolonged use of GPAs on treatment cost.
  Alimentary Pharmacology & Therapeutics 01/2004; 18(11-12):1137-47. · 3.77 Impact Factor
• Source

  Available from: oxfordjournals.org

  Article: Underutilization of preventive strategies in patients receiving NSAIDs.

  M C J M Sturkenboom, T A Burke, J P Dieleman, M J D Tangelder, F Lee, J L Goldstein
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  ABSTRACT: Multiple treatment guidelines for non-steroidal anti-inflammatory drugs (NSAIDs) suggest that patients with one or more risk factors for NSAID-associated upper gastrointestinal (UGI) ulcer complications should be prescribed preventive strategies such as acid-suppressive drugs, misoprostol or cyclooxygenase (COX)-2-specific inhibitors to reduce their risk of serious ulcer complications. The purpose of the present study was to evaluate the extent to which new NSAID users receive recommended preventive strategies and to assess the association between risk factors and a prescription of acid suppressive drugs or misoprostol. A retrospective observational cohort study was conducted using the Integrated Primary Care Information (IPCI) database, a longitudinal database of electronic general practitioner patient records in The Netherlands. The study population comprised all new NSAID users, defined as users of non-specific NSAIDs, COX-2-preferential NSAIDs and COX-2-specific inhibitors, during the period from January 1996 to April 2002. Subjects were excluded if they had an H2-receptor antagonist (H2RA), proton pump inhibitor (PPI) or misoprostol prescription in the 3 months prior to the first NSAID prescription. Preventive use of acid-suppressive drugs or misoprostol was identified by the coprescription for these drugs on the same day (+/-2 days) as the NSAID prescription. The drug use for each patient was validated as having a preventive indication by reviewing the physician-recorded symptoms and diagnoses. Risk factors for UGI ulcer events were defined as age >65 yr, UGI history (gastroduodenal ulcer, UGI bleeding, dyspepsia) and concomitant medications (anticoagulants, aspirin, oral corticosteroids). The study population comprised 69 648 new NSAID users. Overall, 7.9% of NSAID users received a preventive strategy (6.6% received a gastroprotective agent and an additional 1.3% received COX-2-specific inhibitors). Patients using preventive drugs had higher odds of having one or more UGI risk factors than patients without preventive drugs [adjusted odds ratio (OR) 1.78, 95% confidence interval 1.66-1.92]. Despite the greater rate of preventive drug prescriptions in patients who may have been at higher risk, 86.6% of patients with one risk factor and 81.2% with two or more risk factors received no preventive strategies. In contrast to non-specific NSAIDs, patients who received a prescription for a COX-2-specific inhibitor had significantly lower adjusted odds (OR = 0.22) of having H2RA/PPI or misoprostol coprescribed. Although patients who are treated with preventive strategies have higher odds of having gastrointestinal risk factors than those not prescribed preventive therapies, the majority (>80%) of patients with one or more gastrointestinal risk factors do not receive the recommended NSAID treatment regimen of a COX-2-specific inhibitor or NSAID + H2RA/PPI or misoprostol and are therefore undertreated.
  Rheumatology 12/2003; 42 Suppl 3:iii23-31. · 4.06 Impact Factor
• Article: Channelling bias and the incidence of gastrointestinal haemorrhage in users of meloxicam, coxibs, and older, non-specific non-steroidal anti-inflammatory drugs.

  T M MacDonald, S V Morant, J L Goldstein, T A Burke, D Pettitt
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  ABSTRACT: Although clinical trial results suggest that meloxicam has less gastrointestinal toxicity than most other non-steroidal anti-inflammatory drugs (NSAIDs), in practice it has been associated with a large number of yellow card reports of gastrointestinal complications. To estimate whether meloxicam and the coxibs, rofecoxib and celecoxib, have been channelled towards high risk patients, and to estimate the risk of hospitalisation for gastrointestinal haemorrhage associated with the use of these drugs, allowing for the effects of channelling. Using the UK General Practice Research Database, this study included 7.1 thousand patient years (tpy) exposure to meloxicam, 1.6 tpy exposure to coxibs, and 628 tpy exposure to older non-specific NSAIDs. Cohort study of patients who received a prescription for an NSAID between June 1987 and January 2001. Exposure to newer NSAIDs (meloxicam, rofecoxib, celecoxib) and to older non-specific NSAIDs was identified. Channelling was assessed on factors including: demographic variables; diagnosis of arthritis; history of NSAID use or gastrointestinal events, including gastrointestinal haemorrhage; and use of ulcer healing drugs. Most risk factors for gastrointestinal haemorrhage were more prevalent among patients prescribed the newer NSAIDs. Adjusting for these risk factors reduced the relative risks of gastrointestinal haemorrhage on meloxicam and coxibs versus older non-specific NSAIDs to 0.84 (95% confidence interval 0.60, 1.17) and 0.36 (0.14, 0.97), respectively. Channelling towards high risk gastrointestinal patients occurred in the prescribing of newer NSAIDs. After attempting to correct for channelling bias, coxib exposure, but not meloxicam exposure, was associated with a significantly lower risk of gastrointestinal haemorrhage than older non-specific NSAID exposure.
  Gut 10/2003; 52(9):1265-70. · 10.11 Impact Factor
• Article: A comparison of the upper gastrointestinal mucosal effects of valdecoxib, naproxen and placebo in healthy elderly subjects.

  J L Goldstein, A J Kivitz, K M Verburg, D P Recker, R C Palmer, J D Kent
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  ABSTRACT: In long-term outcomes studies, cyclooxygenase COX-2 specific inhibitors spare COX-1 at supratherapeutic doses and therefore demonstrate improved gastrointestinal safety over nonspecific nonsteroidal anti-inflammatory drugs (NSAIDs). However, in clinical practice, anti-inflammatory drugs are often used for short-term treatment of pain. To compare the short-term upper gastrointestinal mucosal effects of naproxen with the new COX-2 specific inhibitor, valdecoxib, or placebo, in elderly subjects. In this multicentre, double-blind, randomized, study, elderly subjects (65-76 years old), with a normal baseline esophagogastroduodenoscopy (EGD), received oral valdecoxib (a supratherapeutic 40 mg b.d. dosage, n = 62), naproxen (500 mg b.d., n = 62), or placebo (n = 62) for 6.5 days. Upper gastrointestinal mucosal injury was evaluated post-treatment by EGD (day 7). Subjects receiving naproxen (11/60, 18%) had significantly more gastroduodenal ulcers post-treatment than those receiving placebo (2/61, 3%; P < 0.01) or valdecoxib (0/60, 0%; P < 0.001). A similar significant finding was observed for gastric ulcer rates. All treatments had similar adverse event rates and clinical laboratory findings. Valdecoxib, even at supratherapeutic doses, was associated with an ulcer rate significantly lower than naproxen but similar to placebo in healthy elderly subjects, despite the short duration of therapy (6.5 days). Naproxen and valdecoxib were as well tolerated as placebo.
  Alimentary Pharmacology & Therapeutics 08/2003; 18(1):125-32. · 3.77 Impact Factor
• Article: Dyspepsia tolerability from the patients' perspective: a comparison of celecoxib with diclofenac.

  J L Goldstein, G M Eisen, T A Burke, B M Peña, J Lefkowith, G S Geis
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  ABSTRACT: To compare celecoxib (800 mg/day, n=1997) with diclofenac (150 mg/day, n=1996) on dyspepsia-related tolerability. In one of the two protocols comprising the Celecoxib Long-Term Arthritis Safety Study, a randomized double-blind trial, patients completed the Severity of Dyspepsia Assessment Questionnaire at baseline and at weeks 4, 13, 26 and 52 for the following three scales: Pain Intensity, Non-Pain Symptoms and Satisfaction with Dyspepsia-Related Health. For the Pain Intensity scale, patients given diclofenac had significantly higher (worsening dyspepsia) mean changes, defined as follow-up minus baseline, than patients given celecoxib (P < 0.001, at all assessments). The mean changes in the Pain Intensity scale (scale, 2-47; higher score is higher pain intensity) were 0.99 (95% confidence interval (CI): 0.50, 1.48) for celecoxib and 2.76 (95% CI: 2.28, 3.25) for diclofenac at 4 weeks. Satisfaction was superior with celecoxib at all assessments (P < 0.001). At 4 weeks, the mean changes in the Satisfaction scale (scale, 7-35; higher score is higher satisfaction) were 0.02 (95% CI: - 0.26, 0.29) for celecoxib and - 0.72 (95% CI: - 1.00, - 0.45) for diclofenac. Diclofenac patients had significantly higher Non-Pain Symptoms at 4 weeks (P=0.005). Celecoxib, at two to four times the recommended dose, demonstrated a superior dyspepsia-related tolerability and satisfaction compared with standard dosages of diclofenac.
  Alimentary Pharmacology & Therapeutics 04/2002; 16(4):819-27. · 3.77 Impact Factor
• Article: Reduced incidence of gastroduodenal ulcers with celecoxib, a novel cyclooxygenase-2 inhibitor, compared to naproxen in patients with arthritis.

  J L Goldstein, P Correa, W W Zhao, A M Burr, R C Hubbard, K M Verburg, G S Geis
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  ABSTRACT: Nonsteroidal anti-inflammatory drugs (NSAIDs) block prostaglandin production by inhibiting cyclooxygenase (COX); they are believed to cause gastroduodenal damage by inhibiting the COX-1 isoform and to have analgesic and anti-inflammatory effects by inhibiting the COX-2 isoform. As compared to conventional NSAIDs, celecoxib, a COX-2 specific inhibitor, has been shown in previous single posttreatment endoscopy studies to be associated with lower gastroduodenal ulcer rates. In response to concerns that such studies may under-represent ulceration rates, the present serial endoscopy study was designed to compare cumulative gastroduodenal ulcer rates associated with the use of celecoxib to those of naproxen, a conventional NSAID. In this double-blind, parallel-group, multicenter study, 537 patients with osteoarthritis (OA) or rheumatoid arthritis (RA) were randomized to treatment with celecoxib 200 mg b.i.d. (n = 270) or naproxen 500 mg b.i.d. (n = 267) for 12 wk. Gastroduodenal damage was determined from esophagogastroduodenoscopy after 4, 8, and 12 wk of therapy. Arthritis efficacy was evaluated with Patient's and Physician's Global Assessments. Gastroduodenal ulcer rates after celecoxib and naproxen treatment were 4% versus 19% in the 0-4 wk interval (p < 0.001), 2% versus 14% in the 4-8 wk interval (p < 0.001), and 2% versus 10% in the 8-12 wk interval (p < 0.001), respectively. After 12 wk of treatment, the cumulative incidence of gastroduodenal ulcers was 9% with celecoxib and 41% with naproxen. In the celecoxib group, gastroduodenal ulcers were significantly associated with Helicobacter pylori status (p < 0.05), concurrent aspirin usage (p = 0.001), and a history of ulcer (p = 0.010), but not with disease type (OA/RA), age, gender, other relevant medical histories, or concurrent corticosteroid or disease-modifying antirheumatic drugs usage (p > 0.05). Celecoxib produced a significantly lower incidence rate of both gastric (p < 0.001) and duodenal (p < 0.030) ulcers. The two agents produced similar improvements in Patient's and Physician's Global Assessments of arthritis efficacy. The incidence of adverse events and withdrawal rates did not differ significantly between treatments. As compared to naproxen (500 mg b.i.d.), use of celecoxib (200 mg b.i.d.), a COX-2 specific agent, at the recommended RA dose and twice the most frequently prescribed OA dose, was associated with lower rates of gastric, duodenal, and gastroduodenal ulcers but had comparable efficacy, in patients with OA and RA.
  The American Journal of Gastroenterology 04/2001; 96(4):1019-27. · 7.28 Impact Factor
• Article: A framework for evaluating the clinical consequences of initial therapy with NSAIDs, NSAIDs plus gastroprotective agents, or celecoxib in the treatment of arthritis.

  T A Burke, R A Zabinski, D Pettitt, N Maniadakis, C J Maurath, J L Goldstein
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  ABSTRACT: The purpose of this study is to provide a framework for estimating the economic efficiency of nonselective nonsteroidal anti-inflammatory drugs (NSAIDs), concomitant gastroprotective agents (GPAs) to reduce the risk of NSAID toxicity, and celecoxib, a specific cyclo-oxygenase-2 inhibitor. Concomitant GPA therapies considered include one of the following: proton pump inhibitors (PPIs) plus NSAIDs, histamine H2 receptor antagonists (H2RAs) plus NSAIDs, misoprostol plus NSAIDs, and a single tablet formulation of diclofenac/misoprostol. The study employs a decision-tree framework to establish probabilities of upper gastrointestinal (GI) adverse events occurring over a 6-month time frame. Celecoxib clinical trial data are used to establish probabilities of upper GI events for celecoxib and NSAIDs, and published literature is used to predict upper GI events for the other concomitant therapies. Upper GI adverse events included in the decision-tree are as follows: GI discomfort, symptomatic ulcer, serious GI complications (with and without death), and anaemia with occult bleeding. Clinical probabilities indicate celecoxib has significant tolerability and safety advantages compared with nonselective NSAIDs. Celecoxib also reduces the risk of GI adverse events to a similar or superior degree when compared with reductions observed with NSAIDs with concomitant GPAs. Use of celecoxib is expected to significantly reduce the economic costs of GI toxicity and its associated morbidity.
  PharmacoEconomics 02/2001; 19 Suppl 1:33-47. · 2.66 Impact Factor
• Source

  Available from: oxfordjournals.org

  Article: Overview of the arthritis Cost Consequence Evaluation System (ACCES): a pharmacoeconomic model for celecoxib.

  D Pettitt, J L Goldstein, A McGuire, J S Schwartz, T Burke, N Maniadakis
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  ABSTRACT: Pharmacoeconomic analyses have become useful and essential tools for health care decision makers who increasingly require such analyses prior to placing a drug on a national, regional or hospital formulary. Previous health economic models of non-steroidal anti-inflammatory drugs (NSAIDs) have been restricted to evaluating a narrow range of agents within specific health care delivery systems using medical information derived from homogeneous clinical trial data. This paper summarizes the Arthritis Cost Consequence Evaluation System (ACCES)--a pharmacoeconomic model that has been developed to predict and evaluate the costs and consequences associated with the use of celecoxib in patients with arthritis, compared with other NSAIDs and NSAIDs plus gastroprotective agents. The advantage of this model is that it can be customized to reflect local practice patterns, resource utilization and costs, as well as provide context-specific health economic information to a variety of providers and/or decision makers.
  Rheumatology 01/2001; 39 Suppl 2:33-42; discussion 57-9. · 4.06 Impact Factor
• Article: Gastrointestinal toxicity with celecoxib vs nonsteroidal anti-inflammatory drugs for osteoarthritis and rheumatoid arthritis: the CLASS study: A randomized controlled trial. Celecoxib Long-term Arthritis Safety Study.

  F E Silverstein, G Faich, J L Goldstein, L S Simon, T Pincus, A Whelton, R Makuch, G Eisen, N M Agrawal, W F Stenson, A M Burr, W W Zhao, J D Kent, J B Lefkowith, K M Verburg, G S Geis
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  ABSTRACT: Conventional nonsteroidal anti-inflammatory drugs (NSAIDs) are associated with a spectrum of toxic effects, notably gastrointestinal (GI) effects, because of inhibition of cyclooxygenase (COX)-1. Whether COX-2-specific inhibitors are associated with fewer clinical GI toxic effects is unknown. To determine whether celecoxib, a COX-2-specific inhibitor, is associated with a lower incidence of significant upper GI toxic effects and other adverse effects compared with conventional NSAIDs. The Celecoxib Long-term Arthritis Safety Study (CLASS), a double-blind, randomized controlled trial conducted from September 1998 to March 2000. Three hundred eighty-six clinical sites in the United States and Canada. A total of 8059 patients (>/=18 years old) with osteoarthritis (OA) or rheumatoid arthritis (RA) were enrolled in the study, and 7968 received at least 1 dose of study drug. A total of 4573 patients (57%) received treatment for 6 months. Patients were randomly assigned to receive celecoxib, 400 mg twice per day (2 and 4 times the maximum RA and OA dosages, respectively; n = 3987); ibuprofen, 800 mg 3 times per day (n = 1985); or diclofenac, 75 mg twice per day (n = 1996). Aspirin use for cardiovascular prophylaxis (</=325 mg/d) was permitted. Incidence of prospectively defined symptomatic upper GI ulcers and ulcer complications (bleeding, perforation, and obstruction) and other adverse effects during the 6-month treatment period. For all patients, the annualized incidence rates of upper GI ulcer complications alone and combined with symptomatic ulcers for celecoxib vs NSAIDs were 0.76% vs 1.45% (P =.09) and 2. 08% vs 3.54% (P =.02), respectively. For patients not taking aspirin, the annualized incidence rates of upper GI ulcer complications alone and combined with symptomatic ulcers for celecoxib vs NSAIDs were 0.44% vs 1.27% (P =.04) and 1.40% vs 2.91% (P =.02). For patients taking aspirin, the annualized incidence rates of upper GI ulcer complications alone and combined with symptomatic ulcers for celecoxib vs NSAIDs were 2.01% vs 2.12% (P =.92) and 4.70% vs 6.00% (P =.49). Fewer celecoxib-treated patients than NSAID-treated patients experienced chronic GI blood loss, GI intolerance, hepatotoxicity, or renal toxicity. No difference was noted in the incidence of cardiovascular events between celecoxib and NSAIDs, irrespective of aspirin use. In this study, celecoxib, at dosages greater than those indicated clinically, was associated with a lower incidence of symptomatic ulcers and ulcer complications combined, as well as other clinically important toxic effects, compared with NSAIDs at standard dosages. The decrease in upper GI toxicity was strongest among patients not taking aspirin concomitantly. JAMA. 2000;284:1247-1255
  JAMA The Journal of the American Medical Association 10/2000; 284(10):1247-55. · 30.03 Impact Factor