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Safety of cyclooxygenase-2 inhibitors in osteoarthritis: Outcomes of a systematic review and meta-analysis

Safety of cyclooxygenase-2 inhibitors in osteoarthritis: Outcomes of a systematic review and meta-analysis
Safety of cyclooxygenase-2 inhibitors in osteoarthritis: Outcomes of a systematic review and meta-analysis

Objective: Our aim was to assess the safety of cyclooxygenase-2 (COX-2) inhibitors in the management of osteoarthritis (OA) in a systematic review and meta-analysis of randomized, placebo-controlled trials. Methods: A comprehensive literature search was undertaken in the databases MEDLINE, Cochrane Central Register of Controlled Trials (Ovid CENTRAL) and Scopus. Randomized, double-blind, placebo-controlled, parallel-group trials that assessed adverse events (AEs) with COX-2 inhibitors in patients with OA were eligible for inclusion. Two authors appraised titles, abstracts and full-text papers for suitability and then assessed the studies for random sequence generation, allocation concealment, blinding of participants and personnel, blinding of outcome assessment, incomplete outcome data and selective outcomes reporting. The primary outcomes of interest were gastrointestinal disorders, cardiac disorders, vascular disorders, nervous system disorders, skin and subcutaneous tissue disorders, hepatobiliary disorders, renal and urinary disorders, as well as overall severe and serious AEs, drug-related AEs and mortality. Secondary outcomes were withdrawals due to AEs (i.e. the number of participants who stopped the treatment due to an AE) and total number of AEs (i.e. the number of patients who experienced any AE at least once). Results: Database searches identified 2149 records from which, after exclusions, 40 trials were included in the meta-analysis. The use of COX-2 inhibitors in OA was associated with a significant increased risk of drug-related AEs compared with placebo (relative risk (RR) 1.26, 95% CI 1.09–1.46; I 2 = 24%). The risk of upper gastrointestinal complications (including dyspepsia, gastritis and heartburn) was significantly increased with COX-2 inhibitors versus placebo (RR 1.19, 95% CI 1.03–1.38; I 2 = 0%), particularly for abdominal pain, which increased by 40% with COX-2 inhibitors (RR 1.40, 95% CI 1.08–1.80; I 2 = 0%). The risk of hypertension increased by 45% overall (RR 1.45, 95% CI 1.01–2.10; I 2 = 25%); however, when rofecoxib was removed from the analysis the risk of hypertension in the COX-2 inhibitor group was no longer significant (RR 1.21, 95% CI 0.80–1.83; I 2 = 20%). The overall risk of heart failure and edema was increased by nearly 70% with COX-2 inhibitors versus placebo (RR 1.68, 95% CI 1.22–2.31; 0%) and this level of risk did not change appreciably when rofecoxib was excluded (RR 1.67, 95% CI 1.21–2.29; 0%). Conclusions: In our analysis, COX-2 inhibitors were associated with an increased risk of upper gastrointestinal AEs, especially abdominal pain. We also found an increased risk of cardiovascular AEs with COX-2 inhibitors, namely hypertension, heart failure and edema.

1170-229X
25-44
Curtis, Elizabeth
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Fuggle, Nicholas
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Shaw, Sarah
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Spooner, Laura
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Ntani, Georgia
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Parsons, Camille
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Corp, Nadia
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Honvo, Germain
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Baird, Janis
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Maggi, Stefania
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Dennison, Elaine
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Bruyère, Olivier
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Reginster, Jean Yves
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Cooper, Cyrus
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Curtis, Elizabeth
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Fuggle, Nicholas
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Shaw, Sarah
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Spooner, Laura
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Ntani, Georgia
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Parsons, Camille
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Corp, Nadia
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Honvo, Germain
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Baird, Janis
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Maggi, Stefania
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Dennison, Elaine
ee647287-edb4-4392-8361-e59fd505b1d1
Bruyère, Olivier
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Reginster, Jean Yves
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Cooper, Cyrus
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Curtis, Elizabeth, Fuggle, Nicholas, Shaw, Sarah, Spooner, Laura, Ntani, Georgia, Parsons, Camille, Corp, Nadia, Honvo, Germain, Baird, Janis, Maggi, Stefania, Dennison, Elaine, Bruyère, Olivier, Reginster, Jean Yves and Cooper, Cyrus (2019) Safety of cyclooxygenase-2 inhibitors in osteoarthritis: Outcomes of a systematic review and meta-analysis. Drugs and Aging, 36, 25-44. (doi:10.1007/s40266-019-00664-x).

Record type: Review

Abstract

Objective: Our aim was to assess the safety of cyclooxygenase-2 (COX-2) inhibitors in the management of osteoarthritis (OA) in a systematic review and meta-analysis of randomized, placebo-controlled trials. Methods: A comprehensive literature search was undertaken in the databases MEDLINE, Cochrane Central Register of Controlled Trials (Ovid CENTRAL) and Scopus. Randomized, double-blind, placebo-controlled, parallel-group trials that assessed adverse events (AEs) with COX-2 inhibitors in patients with OA were eligible for inclusion. Two authors appraised titles, abstracts and full-text papers for suitability and then assessed the studies for random sequence generation, allocation concealment, blinding of participants and personnel, blinding of outcome assessment, incomplete outcome data and selective outcomes reporting. The primary outcomes of interest were gastrointestinal disorders, cardiac disorders, vascular disorders, nervous system disorders, skin and subcutaneous tissue disorders, hepatobiliary disorders, renal and urinary disorders, as well as overall severe and serious AEs, drug-related AEs and mortality. Secondary outcomes were withdrawals due to AEs (i.e. the number of participants who stopped the treatment due to an AE) and total number of AEs (i.e. the number of patients who experienced any AE at least once). Results: Database searches identified 2149 records from which, after exclusions, 40 trials were included in the meta-analysis. The use of COX-2 inhibitors in OA was associated with a significant increased risk of drug-related AEs compared with placebo (relative risk (RR) 1.26, 95% CI 1.09–1.46; I 2 = 24%). The risk of upper gastrointestinal complications (including dyspepsia, gastritis and heartburn) was significantly increased with COX-2 inhibitors versus placebo (RR 1.19, 95% CI 1.03–1.38; I 2 = 0%), particularly for abdominal pain, which increased by 40% with COX-2 inhibitors (RR 1.40, 95% CI 1.08–1.80; I 2 = 0%). The risk of hypertension increased by 45% overall (RR 1.45, 95% CI 1.01–2.10; I 2 = 25%); however, when rofecoxib was removed from the analysis the risk of hypertension in the COX-2 inhibitor group was no longer significant (RR 1.21, 95% CI 0.80–1.83; I 2 = 20%). The overall risk of heart failure and edema was increased by nearly 70% with COX-2 inhibitors versus placebo (RR 1.68, 95% CI 1.22–2.31; 0%) and this level of risk did not change appreciably when rofecoxib was excluded (RR 1.67, 95% CI 1.21–2.29; 0%). Conclusions: In our analysis, COX-2 inhibitors were associated with an increased risk of upper gastrointestinal AEs, especially abdominal pain. We also found an increased risk of cardiovascular AEs with COX-2 inhibitors, namely hypertension, heart failure and edema.

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e-pub ahead of print date: 9 May 2019

Identifiers

Local EPrints ID: 431435
URI: http://eprints.soton.ac.uk/id/eprint/431435
ISSN: 1170-229X
PURE UUID: 4127241b-9710-46f5-801c-a85d648b164b
ORCID for Elizabeth Curtis: ORCID iD orcid.org/0000-0002-5147-0550
ORCID for Sarah Shaw: ORCID iD orcid.org/0000-0002-2206-6858
ORCID for Janis Baird: ORCID iD orcid.org/0000-0002-4039-4361
ORCID for Elaine Dennison: ORCID iD orcid.org/0000-0002-3048-4961
ORCID for Cyrus Cooper: ORCID iD orcid.org/0000-0003-3510-0709

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Date deposited: 03 Jun 2019 16:30
Last modified: 26 Nov 2021 03:09

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Contributors

Author: Nicholas Fuggle
Author: Sarah Shaw ORCID iD
Author: Laura Spooner
Author: Georgia Ntani
Author: Camille Parsons
Author: Nadia Corp
Author: Germain Honvo
Author: Janis Baird ORCID iD
Author: Stefania Maggi
Author: Elaine Dennison ORCID iD
Author: Olivier Bruyère
Author: Jean Yves Reginster
Author: Cyrus Cooper ORCID iD

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