Comparison of upper gastrointestinal toxicity of rofecoxib and naproxen in patients with rheumatoid arthritis (original) (raw)
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Gastroenterology, 2002
Background & Aims: Epidemiologic data indicate that the risk of nonsteroidal anti-inflammatory drug (NSAID)related gastrointestinal (GI) clinical events varies based on patients' clinical characteristics. The authors determined risk factors for NSAID-related clinical upper GI events and the event rates, absolute risk reductions, and numbers needed to treat for individual risk factors for a nonselective NSAID and a selective cyclooxygenase 2 inhibitor in a double-blind outcomes trial. Methods: Eight thousand seventy-six rheumatoid arthritis patients aged >50 years (or >40 on corticosteroid therapy) were randomly assigned to rofecoxib 50 mg daily or naproxen 500 mg twice daily for a median of 9 months. The development of clinical upper GI events (bleeding, perforation, obstruction, and symptomatic ulcer identified on clinically indicated work-up) was assessed. Results: Significant risk factors included prior upper GI events, age >65, and severe rheumatoid arthritis (RR, 2.3-3.9). Patients administered naproxen who had prior upper GI complications or who were aged >75 years had 18.84 or 14.46 events per 100 patient-years, and the risk of events remained constant over time. The reduction in events with rofecoxib was similar in high-and low-risk subgroups (RR, 0.31-0.68). The number needed to treat with rofecoxib instead of naproxen to avert 1 GI event was 10-12 in highest risk patients (prior event, age >75 years, or severe rheumatoid arthritis), 17-33 in patients with other risk factors, and 42-106 in low-risk patients. Conclusions: NSAID-related GI events increase dramatically with risk factors such as prior events or older age. Ten to twelve high-risk patients need to be treated with a protective strategy such as the selective cyclooxygenase 2 inhibitor, rofecoxib, to avert a clinical GI event.
Clinical Therapeutics, 1999
Nonsteroidal anti-inflammatory drugs (NSAIDs) inhibit both cyclooxygenase (COX)-1 and COX-2 isoenzymes and are effective in the treatment of inflammatory disorders. This 8-week, double-masked, placebo-controlled trial was undertaken to assess the safety profile, tolerability, and effective dose range of once-daily rofecoxib, a COX-2-specific inhibitor, in the treatment of rheumatoid arthritis (RA). After a 3- to 15-day washout of prior NSAID therapy,
Clinical experience with cyclooxygenase-2 inhibitors
Inflammation Research, 1999
Rheumatoid arthritis (RA) and osteoarthritis (OA) are chronic conditions requiring long-term therapy for pain relief. Currently prescribed non-steroidal anti-inflammatory drugs (NSAIDs) provide symptomatic efficacy, but are frequently associated with gastrointestinal (GI) toxicities such as dyspepsia and ulcerations. In a small but significant number of cases, complications including perforations and massive bleeding develop and these may be fatal. A desirable therapeutic strategy would maintain efficacy while minimizing gastric intolerance. Two potential approaches have been suggested: (i) administration of NSAIDs in combination with gastroprotective compounds; or (ii) administration of potentially safer anti-inflammatory compounds which act via selective inhibition of cyclooxygenase-2 (COX-2). The selective COX-2 inhibitors rofecoxib and celecoxib consistently demonstrate efficacy comparable to conventional NSAIDs in patients with RA and OA, but have a significantly reduced propensity to cause GI toxicity. In many cases, the gastric effects of therapeutically active doses of COX-2 inhibitors are indistinguishable from placebo. The safety benefits of COX-2 inhibitors given alone appear similar to combined therapy with conventional NSAIDs and gastroprotective agents. Findings warrant the consideration of COX-2 inhibitors as first-line therapy in patients requiring long-term pain relief.
Arthritis Research & Therapy - ARTHRITIS RES THER, 2003
BackgroundNonsteroidal anti-inflammatory drug (NSAID) gastropathy is recognized as a major cause of hospitalizations and deaths, with more than 100,000 annual hospitalizations and more than 10,000 annual deaths in the United States alone. Trends in this epidemic over time have not been examined.ObjectiveWe studied the possibility that new preventive approaches to NSAID gastropathy may have reduced the magnitude of this epidemic.MethodsWe studied 5598 patients with rheumatoid arthritis from longitudinal data banks previously employed to help establish the epidemiology of NSAID gastropathy. Consecutively enrolled patients were followed with bi-annual Health Assessment Questionnaire assessments and medical record audits between 1981 and 2000. Annual rates of hospitalization involving gastrointestinal (GI) bleeding, obstruction, or perforation were calculated and curves fitted using spline regression.ResultsAnnual GI hospitalization rates rose from 0.6% in 1981 to a peak of 1.5% in 1992, t ...
Alimentary Pharmacology & Therapeutics, 2018
Aim: To evaluate GI safety of celecoxib compared with 2 nonselective (ns) NSAIDs, as a secondary objective of a large trial examining multiorgan safety. Methods: This randomised, double-blind controlled trial analysed 24 081 patients. Osteoarthritis or rheumatoid arthritis patients, needing ongoing NSAID treatment, were randomised to receive celecoxib 100-200 mg b.d., ibuprofen 600-800 mg t.d.s. or naproxen 375-500 mg b.d. plus esomeprazole, and low-dose aspirin or corticosteroids if already prescribed. Clinically significant GI events (CSGIE-bleeding, obstruction, perforation events from stomach downwards or symptomatic ulcers) and iron deficiency anaemia (IDA) were adjudicated blindly. Results: Mean treatment and follow-up durations were 20.3 and 34.1 months. While on treatment or 30 days after, CSGIE occurred in 0.34%, 0.74% and 0.66% taking celecoxib, ibuprofen and naproxen. Hazard ratios (HR) were 0.43 (95% CI 0.27-0.68, P = 0.0003) celecoxib vs ibuprofen and 0.51 (0.32-0.81, P = 0.004) vs naproxen. There was also less IDA on celecoxib: HR 0.43 (0.27-0.68, P = 0.0003) vs ibuprofen; 0.40 (0.25-0.62, P < 0.0001) vs naproxen. Even taken with low-dose aspirin, fewer CSGIE occurred on celecoxib than ibuprofen (HR 0.52 [0.29-0.94], P = 0.03), and less IDA vs naproxen (0.42 [0.23-0.77, P = 0.005]). Corticosteroid use increased total GI events and CSGIE. H. pylori serological status had no influence. Conclusions: Arthritis patients taking NSAIDs plus esomeprazole have infrequent clinically significant gastrointestinal events. Co-prescribed with esomeprazole, celecoxib has better overall GI safety than ibuprofen or naproxen at these doses, despite treatment with low-dose aspirin or corticosteroids. For the full list of investigators see Appendix S2. The Handling Editor for this article was Professor Colin Howden, and it was accepted for publication after full peer-review.