Clinical research study
Celecoxib Versus Naproxen and Diclofenac in Osteoarthritis Patients: SUCCESS-I Study

https://doi.org/10.1016/j.amjmed.2005.09.054Get rights and content

Abstract

Purpose

To evaluate the efficacy and upper gastrointestinal (UGI) safety of celecoxib, compared with nonspecific nonsteroidal anti-inflammatory drugs (NSAIDs), among patients with osteoarthritis.

Methods

A total of 13 274 osteoarthritis patients from 39 countries were randomly assigned to double-blind treatment with either celecoxib 100 mg twice daily (BID), celecoxib 200 mg BID, or nonselective NSAID therapy (diclofenac 50 mg BID or naproxen 500 mg BID) for 12 weeks. Standard validated measures were used to assess osteoarthritis efficacy. Serious UGI events were evaluated by 2 blinded, independent, gastrointestinal events committees.

Results

Results from all primary efficacy assessments showed that both dosages of celecoxib were as effective as NSAIDs in treating osteoarthritis. Significantly more ulcer complications occurred within the nonselective NSAID group (0.8/100 patient-years) compared with the celecoxib group (0.1/100 patient-years) (odds ratio = 7.02; 95% confidence interval [CI], 1.46 to 33.80; P =.008). There were fewer ulcer complications in the celecoxib group compared with the NSAID group, both in patients taking concomitant aspirin and those not taking aspirin, but the difference reached statistical significance only in the latter comparison. The number of cardiovascular thromboembolic events was low and not statistically different between the groups (eg, myocardial infarction rates: celecoxib 10 events [0.55/100 patient-years] vs NSAIDs 1 event [0.11/100 patient-years], (P =.11), but the study was not powered to detect such differences.

Conclusions

In the treatment of osteoarthritis, celecoxib is as effective as the nonspecific NSAIDs naproxen and diclofenac, but has significantly fewer serious upper gastrointestinal events.

Section snippets

Patients

The SUCCESS-1 study was specifically designed with inclusion and exclusion criteria that would yield a study population representative of osteoarthritis patients in community-based, outpatient, clinical practices in each of the participating countries. Eligible patients were aged 18 years or older; had osteoarthritis of the hip, knee, or hand (meeting American College of Rheumatology classification criteria) of at least 6 months duration before randomization; required daily anti-inflammatory

Results

A total of 13 274 patients from 1142 study centers in 39 countries were randomized. Of these patients, 13 194 received at least 1 dose of study medication (intention-to-treat cohort): 4393 celecoxib 100 mg twice daily, 4407 celecoxib 200 mg twice daily, 905 naproxen 500 mg twice daily, and 3489 diclofenac 50 mg twice daily. Geographically, 6511 patients were from Europe and South Africa, 2873 from Latin America, 2736 from the U.S. and Canada, 681 from Asia, and 393 from Australia and New Zealand.

Discussion

We found that celecoxib 100 mg twice daily was comparable to naproxen and diclofenac for relief of the signs and symptoms of osteoarthritis of the knee, hip, or hand. Additionally, celecoxib 100 mg twice daily and 200 mg twice daily were similar in efficacy. We found a significant reduction in serious upper gastrointestinal events in celecoxib-treated patients compared with patients on naproxen or diclofenac.

These results are important considering that differing conclusions with regard to

Acknowledgments

We are indebted to the SUCCESS-1 investigators for their participation in the study, Suzanne P. Boots for her dedication and invaluable assistance in managing the study, and Lorraine R. Baer, PharmD for editorial contributions and assistance in the preparation of the manuscript.

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  • Cited by (0)

    This study was supported by a grant from Pharmacia Corporation and Pfizer, Inc. The study design as well as data analysis and interpretation were performed by the study design committee, of which the sponsor was a member. The study sponsors were responsible for data collection and management, in collaboration with the authors. Two independent Gastrointestinal Events adjudication committees performed the data analysis and interpretation of gastrointestinal events. The authors had full access to all the data and had final responsibility for data analysis, interpretation, manuscript preparation and the decision to submit for publication.

    Conflict of Interest Statement: Gurkirpal Singh received research support from Searle, Pharmacia, Pfizer, Merck, Boehringer Ingelheim, TAP Pharmaceuticals, Wyeth, Altana, Glaxo Smith Kline, Novartis, and Centocor; consultancies, travel grants, speakers bureau from Searle, Pharmacia, Pfizer, Merck and Boehringer Ingelheim. John G. Fort and Carl Wallmark were employees of Pharmacia/Pfizer and own stock in Pfizer, Inc. Jay L. Goldstein: consultancies, honoraria, travel grants, travel expenses, speakers bureau, and research grants from Searle, Pharmacia, Pfizer, TAP Pharmaceuticals, and Astra-Zeneca. Roger A. Levy: Investigator and Speakers bureau (Pfizer, Aventis, Wyeth and Schering-Plough); Advisory board (Pfizer and Novartis). Patrick S. Hanrahan: travel grants from Pfizer. Alfonso E. Bello: former employee of Pharmacia/Pfizer. Lilia Andrade-Ortega: Advisory board (Pfizer); travel grants (Schering Plough). Naurang M. Agrawal: honoraria (Pharmacia and Pfizer); advisory board (Pfizer). Glenn M. Eisen: consultancies and honoraria (Pfizer). William F. Stenson: consultancies (Pharmacia and Pfizer). George Triadafilopoulos: research support from Pfizer, Astra-Zeneca and TAP Pharmaceuticals; consultant to Pfizer, Merck, Boerhinger-Ingelheim, Astra-Zeneca, TAP Pharmaceuticals, Janssen and Wyeth; honoraria and travel support for lectures and meetings from Pfizer, Merck, Boerhinger-Ingelheim, Astra-Zeneca, TAP Pharmaceuticals, Janssen and Wyeth.

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