Gastrointestinal Tolerability and Effectiveness of Rofecoxib versus Naproxen in the Treatment of Osteoarthritis: A Randomized, Controlled Trial

Jeffrey R Lisse, Monica Perlman, Gunnar Johansson, James R. Shoemaker, Joy Schechtman, Carol S. Skalky, Mary E. Dixon, Adam B. Polis, Arthur J. Mollen, Gregory P. Geba

Research output: Contribution to journalArticle

131 Citations (Scopus)

Abstract

Background: Gastrointestinal (GI) toxicity mediated by dual cyclooxygenase (COX)-1 and COX-2 inhibition of nonsteroidal anti-inflammatory drugs (NSAIDs) can cause serious alterations of mucosal integrity or, more commonly, intolerable GI symptoms that may necessitate discontinuation of therapy. Unlike NSAIDs, rofecoxib targets only the COX-2 isoform. Objective: To assess the tolerability of rofecoxib compared with naproxen for treatment of osteoarthritis. Design: Randomized, controlled trial. Setting: 600 office and clinical research sites. Patients: 5557 patients (mean age, 63 years) with a baseline diagnosis of osteoarthritis of the knee, hip, hand, or spine. Intervention: Rofecoxib, 25 mg/d, or naproxen, 500 mg twice daily. Use of routine medications, including aspirin, was permitted. Measurements: Discontinuation due to GI adverse events (primary end point) and use of concomitant medication to treat GI symptoms (secondary end point). Efficacy was determined by patient-reported global assessment of disease status and the Australian/Canadian Osteoarthritis Hand Index, as well as discontinuations due to lack of efficacy. Patients were evaluated at baseline and at weeks 6 and 12. Results: Rates of cumulative discontinuation due to GI adverse events were statistically significantly lower in the rofecoxib group than in the naproxen group (5.9% vs. 8.1%; relative risk, 0.74 [95% CI, 0.60 to 0.92]; P= 0.005), as were rates of cumulative use of medication to treat GI symptoms (9.1% vs. 11. 2%; relative risk, 0.79 [CI, 0.66 to 0.96]; P = 0.014]). Subgroup analysis of patients who used low-dose aspirin (13%) and those who previously discontinued using arthritis medication because of GI symptoms (15%) demonstrated a relative risk similar to the overall sample for discontinuation due to GI adverse events (relative risk, 0.56 [CI, 0.31 to 1.01] and 0.53 [CI, 0.34 to 0.84], respectively). No statistically significant difference was observed between treatments for efficacy in treating osteoarthritis or for occurrence of other adverse events. Conclusions: In patients with osteoarthritis treated for 12 weeks, rofecoxib, 25 mg/d, was as effective as naproxen, 500 mg twice daily, but had statistically significantly superior GI tolerability and led to less use of concomitant GI medications. Benefits of rofecoxib in subgroup analyses were consistent with findings in the overall sample.

Original languageEnglish (US)
Pages (from-to)539-546+I29
JournalAnnals of Internal Medicine
Volume139
Issue number7
StatePublished - Oct 7 2003
Externally publishedYes

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Naproxen
Osteoarthritis
Randomized Controlled Trials
Cyclooxygenase 2
Aspirin
Anti-Inflammatory Agents
Therapeutics
Hand
Cyclooxygenase 1
Hip Osteoarthritis
Knee Osteoarthritis
Pharmaceutical Preparations
Arthritis
rofecoxib
Protein Isoforms
Spine
Research

ASJC Scopus subject areas

  • Medicine(all)

Cite this

Lisse, J. R., Perlman, M., Johansson, G., Shoemaker, J. R., Schechtman, J., Skalky, C. S., ... Geba, G. P. (2003). Gastrointestinal Tolerability and Effectiveness of Rofecoxib versus Naproxen in the Treatment of Osteoarthritis: A Randomized, Controlled Trial. Annals of Internal Medicine, 139(7), 539-546+I29.

Gastrointestinal Tolerability and Effectiveness of Rofecoxib versus Naproxen in the Treatment of Osteoarthritis : A Randomized, Controlled Trial. / Lisse, Jeffrey R; Perlman, Monica; Johansson, Gunnar; Shoemaker, James R.; Schechtman, Joy; Skalky, Carol S.; Dixon, Mary E.; Polis, Adam B.; Mollen, Arthur J.; Geba, Gregory P.

In: Annals of Internal Medicine, Vol. 139, No. 7, 07.10.2003, p. 539-546+I29.

Research output: Contribution to journalArticle

Lisse, JR, Perlman, M, Johansson, G, Shoemaker, JR, Schechtman, J, Skalky, CS, Dixon, ME, Polis, AB, Mollen, AJ & Geba, GP 2003, 'Gastrointestinal Tolerability and Effectiveness of Rofecoxib versus Naproxen in the Treatment of Osteoarthritis: A Randomized, Controlled Trial', Annals of Internal Medicine, vol. 139, no. 7, pp. 539-546+I29.
Lisse, Jeffrey R ; Perlman, Monica ; Johansson, Gunnar ; Shoemaker, James R. ; Schechtman, Joy ; Skalky, Carol S. ; Dixon, Mary E. ; Polis, Adam B. ; Mollen, Arthur J. ; Geba, Gregory P. / Gastrointestinal Tolerability and Effectiveness of Rofecoxib versus Naproxen in the Treatment of Osteoarthritis : A Randomized, Controlled Trial. In: Annals of Internal Medicine. 2003 ; Vol. 139, No. 7. pp. 539-546+I29.
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abstract = "Background: Gastrointestinal (GI) toxicity mediated by dual cyclooxygenase (COX)-1 and COX-2 inhibition of nonsteroidal anti-inflammatory drugs (NSAIDs) can cause serious alterations of mucosal integrity or, more commonly, intolerable GI symptoms that may necessitate discontinuation of therapy. Unlike NSAIDs, rofecoxib targets only the COX-2 isoform. Objective: To assess the tolerability of rofecoxib compared with naproxen for treatment of osteoarthritis. Design: Randomized, controlled trial. Setting: 600 office and clinical research sites. Patients: 5557 patients (mean age, 63 years) with a baseline diagnosis of osteoarthritis of the knee, hip, hand, or spine. Intervention: Rofecoxib, 25 mg/d, or naproxen, 500 mg twice daily. Use of routine medications, including aspirin, was permitted. Measurements: Discontinuation due to GI adverse events (primary end point) and use of concomitant medication to treat GI symptoms (secondary end point). Efficacy was determined by patient-reported global assessment of disease status and the Australian/Canadian Osteoarthritis Hand Index, as well as discontinuations due to lack of efficacy. Patients were evaluated at baseline and at weeks 6 and 12. Results: Rates of cumulative discontinuation due to GI adverse events were statistically significantly lower in the rofecoxib group than in the naproxen group (5.9{\%} vs. 8.1{\%}; relative risk, 0.74 [95{\%} CI, 0.60 to 0.92]; P= 0.005), as were rates of cumulative use of medication to treat GI symptoms (9.1{\%} vs. 11. 2{\%}; relative risk, 0.79 [CI, 0.66 to 0.96]; P = 0.014]). Subgroup analysis of patients who used low-dose aspirin (13{\%}) and those who previously discontinued using arthritis medication because of GI symptoms (15{\%}) demonstrated a relative risk similar to the overall sample for discontinuation due to GI adverse events (relative risk, 0.56 [CI, 0.31 to 1.01] and 0.53 [CI, 0.34 to 0.84], respectively). No statistically significant difference was observed between treatments for efficacy in treating osteoarthritis or for occurrence of other adverse events. Conclusions: In patients with osteoarthritis treated for 12 weeks, rofecoxib, 25 mg/d, was as effective as naproxen, 500 mg twice daily, but had statistically significantly superior GI tolerability and led to less use of concomitant GI medications. Benefits of rofecoxib in subgroup analyses were consistent with findings in the overall sample.",
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T1 - Gastrointestinal Tolerability and Effectiveness of Rofecoxib versus Naproxen in the Treatment of Osteoarthritis

T2 - A Randomized, Controlled Trial

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AU - Perlman, Monica

AU - Johansson, Gunnar

AU - Shoemaker, James R.

AU - Schechtman, Joy

AU - Skalky, Carol S.

AU - Dixon, Mary E.

AU - Polis, Adam B.

AU - Mollen, Arthur J.

AU - Geba, Gregory P.

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N2 - Background: Gastrointestinal (GI) toxicity mediated by dual cyclooxygenase (COX)-1 and COX-2 inhibition of nonsteroidal anti-inflammatory drugs (NSAIDs) can cause serious alterations of mucosal integrity or, more commonly, intolerable GI symptoms that may necessitate discontinuation of therapy. Unlike NSAIDs, rofecoxib targets only the COX-2 isoform. Objective: To assess the tolerability of rofecoxib compared with naproxen for treatment of osteoarthritis. Design: Randomized, controlled trial. Setting: 600 office and clinical research sites. Patients: 5557 patients (mean age, 63 years) with a baseline diagnosis of osteoarthritis of the knee, hip, hand, or spine. Intervention: Rofecoxib, 25 mg/d, or naproxen, 500 mg twice daily. Use of routine medications, including aspirin, was permitted. Measurements: Discontinuation due to GI adverse events (primary end point) and use of concomitant medication to treat GI symptoms (secondary end point). Efficacy was determined by patient-reported global assessment of disease status and the Australian/Canadian Osteoarthritis Hand Index, as well as discontinuations due to lack of efficacy. Patients were evaluated at baseline and at weeks 6 and 12. Results: Rates of cumulative discontinuation due to GI adverse events were statistically significantly lower in the rofecoxib group than in the naproxen group (5.9% vs. 8.1%; relative risk, 0.74 [95% CI, 0.60 to 0.92]; P= 0.005), as were rates of cumulative use of medication to treat GI symptoms (9.1% vs. 11. 2%; relative risk, 0.79 [CI, 0.66 to 0.96]; P = 0.014]). Subgroup analysis of patients who used low-dose aspirin (13%) and those who previously discontinued using arthritis medication because of GI symptoms (15%) demonstrated a relative risk similar to the overall sample for discontinuation due to GI adverse events (relative risk, 0.56 [CI, 0.31 to 1.01] and 0.53 [CI, 0.34 to 0.84], respectively). No statistically significant difference was observed between treatments for efficacy in treating osteoarthritis or for occurrence of other adverse events. Conclusions: In patients with osteoarthritis treated for 12 weeks, rofecoxib, 25 mg/d, was as effective as naproxen, 500 mg twice daily, but had statistically significantly superior GI tolerability and led to less use of concomitant GI medications. Benefits of rofecoxib in subgroup analyses were consistent with findings in the overall sample.

AB - Background: Gastrointestinal (GI) toxicity mediated by dual cyclooxygenase (COX)-1 and COX-2 inhibition of nonsteroidal anti-inflammatory drugs (NSAIDs) can cause serious alterations of mucosal integrity or, more commonly, intolerable GI symptoms that may necessitate discontinuation of therapy. Unlike NSAIDs, rofecoxib targets only the COX-2 isoform. Objective: To assess the tolerability of rofecoxib compared with naproxen for treatment of osteoarthritis. Design: Randomized, controlled trial. Setting: 600 office and clinical research sites. Patients: 5557 patients (mean age, 63 years) with a baseline diagnosis of osteoarthritis of the knee, hip, hand, or spine. Intervention: Rofecoxib, 25 mg/d, or naproxen, 500 mg twice daily. Use of routine medications, including aspirin, was permitted. Measurements: Discontinuation due to GI adverse events (primary end point) and use of concomitant medication to treat GI symptoms (secondary end point). Efficacy was determined by patient-reported global assessment of disease status and the Australian/Canadian Osteoarthritis Hand Index, as well as discontinuations due to lack of efficacy. Patients were evaluated at baseline and at weeks 6 and 12. Results: Rates of cumulative discontinuation due to GI adverse events were statistically significantly lower in the rofecoxib group than in the naproxen group (5.9% vs. 8.1%; relative risk, 0.74 [95% CI, 0.60 to 0.92]; P= 0.005), as were rates of cumulative use of medication to treat GI symptoms (9.1% vs. 11. 2%; relative risk, 0.79 [CI, 0.66 to 0.96]; P = 0.014]). Subgroup analysis of patients who used low-dose aspirin (13%) and those who previously discontinued using arthritis medication because of GI symptoms (15%) demonstrated a relative risk similar to the overall sample for discontinuation due to GI adverse events (relative risk, 0.56 [CI, 0.31 to 1.01] and 0.53 [CI, 0.34 to 0.84], respectively). No statistically significant difference was observed between treatments for efficacy in treating osteoarthritis or for occurrence of other adverse events. Conclusions: In patients with osteoarthritis treated for 12 weeks, rofecoxib, 25 mg/d, was as effective as naproxen, 500 mg twice daily, but had statistically significantly superior GI tolerability and led to less use of concomitant GI medications. Benefits of rofecoxib in subgroup analyses were consistent with findings in the overall sample.

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