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Safety of opioids in osteoarthritis: Outcomes of systematic review and meta-analysis

Safety of opioids in osteoarthritis: Outcomes of systematic review and meta-analysis
Safety of opioids in osteoarthritis: Outcomes of systematic review and meta-analysis
Objective: We aimed to assess the safety of opioids 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 MEDLINE, Cochrane Central Register of Controlled Trials (Ovid CENTRAL), and Scopus electronic databases. Randomized, double-blind, placebo-controlled, parallel-group trials that assessed adverse events (AEs) with opioids 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 (GI) disorders, cardiac disorders, vascular disorders, nervous system disorders, skin and subcutaneous tissue disorders, renal and urinary disorders, respiratory, thoracic and mediastinal disorders, as well as overall severe and serious AEs and drug-related AEs. 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 2189 records, from which, after exclusions, 17 papers were included in the meta-analysis. More disorders of the lower GI tract (constipation, fecaloma) were reported with both immediate-release (IR) and extended-release (ER) formulations of opioids versus placebo: IR opioids (relative risk [RR] 5.20, 95% confidence interval [CI] 3.42–7.89); ER opioids (RR 4.22, 95% CI 3.44–5.17). The risk of upper GI AEs increased fourfold with ER opioids compared with placebo (RR 4.03, 95% CI 0.87–18.62), and the risk of nausea, vomiting or loss of appetite increased four- to fivefold with both formulations: IR opioids (RR 3.39, 95% CI 2.22–5.18); ER opioids (RR 4.03, 95% CI 3.37–4.83). An increased risk of dermatologic AEs (rash and pruritis; IR opioids: RR 3.60, 95% CI 1.74–7.43; ER opioids: RR 7.87, 95% CI 5.20–11.89) and central nervous system disorders (dizziness, headache, fatigue, somnolence, insomnia; IR opioids: RR 2.76, 95% CI 1.90–4.02; ER opioids: RR 2.76, 95% CI 2.19–3.47) was found with all opioid formulations versus placebo.

Conclusions: Our results confirm that there are considerable safety and tolerability issues surrounding the use of opioids in OA, and support the recommendation of international and national guidelines to use opioids in OA after other analgesic options, and for short time periods.
1170-229X
129-143
Fuggle, Nicholas
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Curtis, Elizabeth
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Shaw, Sarah
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Spooner, Laura
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Bruyère, Olivier
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Ntani, Georgia
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Parsons, Camille
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Conaghan, Philip
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Corp, Nadia
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Honvo, Germain
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Uebelhart, Daniel
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Baird, Janis
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Dennison, Elaine
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Reginster, Jean-Yves
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Cooper, Cyrus
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Fuggle, Nicholas
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Curtis, Elizabeth
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Shaw, Sarah
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Spooner, Laura
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Bruyère, Olivier
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Ntani, Georgia
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Parsons, Camille
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Conaghan, Philip
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Corp, Nadia
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Honvo, Germain
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Uebelhart, Daniel
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Baird, Janis
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Dennison, Elaine
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Reginster, Jean-Yves
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Cooper, Cyrus
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Fuggle, Nicholas, Curtis, Elizabeth, Shaw, Sarah, Spooner, Laura, Bruyère, Olivier, Ntani, Georgia, Parsons, Camille, Conaghan, Philip, Corp, Nadia, Honvo, Germain, Uebelhart, Daniel, Baird, Janis, Dennison, Elaine, Reginster, Jean-Yves and Cooper, Cyrus (2019) Safety of opioids in osteoarthritis: Outcomes of systematic review and meta-analysis. Drugs & Aging, 36 (Supplement 1), 129-143. (doi:10.1007/s40266-019-00666-9).

Record type: Article

Abstract

Objective: We aimed to assess the safety of opioids 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 MEDLINE, Cochrane Central Register of Controlled Trials (Ovid CENTRAL), and Scopus electronic databases. Randomized, double-blind, placebo-controlled, parallel-group trials that assessed adverse events (AEs) with opioids 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 (GI) disorders, cardiac disorders, vascular disorders, nervous system disorders, skin and subcutaneous tissue disorders, renal and urinary disorders, respiratory, thoracic and mediastinal disorders, as well as overall severe and serious AEs and drug-related AEs. 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 2189 records, from which, after exclusions, 17 papers were included in the meta-analysis. More disorders of the lower GI tract (constipation, fecaloma) were reported with both immediate-release (IR) and extended-release (ER) formulations of opioids versus placebo: IR opioids (relative risk [RR] 5.20, 95% confidence interval [CI] 3.42–7.89); ER opioids (RR 4.22, 95% CI 3.44–5.17). The risk of upper GI AEs increased fourfold with ER opioids compared with placebo (RR 4.03, 95% CI 0.87–18.62), and the risk of nausea, vomiting or loss of appetite increased four- to fivefold with both formulations: IR opioids (RR 3.39, 95% CI 2.22–5.18); ER opioids (RR 4.03, 95% CI 3.37–4.83). An increased risk of dermatologic AEs (rash and pruritis; IR opioids: RR 3.60, 95% CI 1.74–7.43; ER opioids: RR 7.87, 95% CI 5.20–11.89) and central nervous system disorders (dizziness, headache, fatigue, somnolence, insomnia; IR opioids: RR 2.76, 95% CI 1.90–4.02; ER opioids: RR 2.76, 95% CI 2.19–3.47) was found with all opioid formulations versus placebo.

Conclusions: Our results confirm that there are considerable safety and tolerability issues surrounding the use of opioids in OA, and support the recommendation of international and national guidelines to use opioids in OA after other analgesic options, and for short time periods.

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Accepted/In Press date: 1 May 2019
e-pub ahead of print date: 9 May 2019

Identifiers

Local EPrints ID: 431597
URI: http://eprints.soton.ac.uk/id/eprint/431597
ISSN: 1170-229X
PURE UUID: 5ad4a72e-8096-440b-87a6-883c4bb191f7
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

Catalogue record

Date deposited: 10 Jun 2019 16:30
Last modified: 26 Nov 2021 06:12

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Contributors

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

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