PMID- 31073926 OWN - NLM STAT- MEDLINE DCOM- 20190708 LR - 20210317 IS - 1179-1969 (Electronic) IS - 1170-229X (Print) IS - 1170-229X (Linking) VI - 36 IP - Suppl 1 DP - 2019 Apr TI - Safety of Opioids in Osteoarthritis: Outcomes of a Systematic Review and Meta-Analysis. PG - 129-143 LID - 10.1007/s40266-019-00666-9 [doi] AB - 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. FAU - Fuggle, Nicholas AU - Fuggle N AD - MRC Lifecourse Epidemiology Unit, University of Southampton, Southampton General Hospital, Tremona Road, Southampton, SO16 6YD, UK. FAU - Curtis, Elizabeth AU - Curtis E AUID- ORCID: 0000-0002-5147-0550 AD - MRC Lifecourse Epidemiology Unit, University of Southampton, Southampton General Hospital, Tremona Road, Southampton, SO16 6YD, UK. FAU - Shaw, Sarah AU - Shaw S AD - MRC Lifecourse Epidemiology Unit, University of Southampton, Southampton General Hospital, Tremona Road, Southampton, SO16 6YD, UK. FAU - Spooner, Laura AU - Spooner L AD - Portsmouth Hospitals NHS Trust, Portsmouth, UK. FAU - Bruyere, Olivier AU - Bruyere O AD - Department of Public Health, Epidemiology and Health Economics, University of Liege, Liege, Belgium. AD - WHO Collaborating Centre for Public Heath Aspects of Musculoskeletal Health and Aging, Liege, Belgium. FAU - Ntani, Georgia AU - Ntani G AD - MRC Lifecourse Epidemiology Unit, University of Southampton, Southampton General Hospital, Tremona Road, Southampton, SO16 6YD, UK. FAU - Parsons, Camille AU - Parsons C AD - MRC Lifecourse Epidemiology Unit, University of Southampton, Southampton General Hospital, Tremona Road, Southampton, SO16 6YD, UK. FAU - Conaghan, Philip G AU - Conaghan PG AD - Leeds Institute of Rheumatic and Musculoskeletal Medicine, University of Leeds and NIHR Leeds Biomedical Research Centre, Leeds Teaching Hospitals NHS Trust, Leeds, UK. FAU - Corp, Nadia AU - Corp N AD - Arthritis Research UK Primary Care Centre, Institute for Primary Care and Health Sciences, Keele University, Keele, UK. FAU - Honvo, Germain AU - Honvo G AD - Department of Public Health, Epidemiology and Health Economics, University of Liege, Liege, Belgium. AD - WHO Collaborating Centre for Public Heath Aspects of Musculoskeletal Health and Aging, Liege, Belgium. FAU - Uebelhart, Daniel AU - Uebelhart D AD - Division of Musculoskeletal, Internal Medicine and Oncological Rehabilitation, Department of Orthopaedics and Traumatology, Hopital du Valais (HVS), Centre Hospitalier du Valais Romand (CHVR), CVP, Crans-Montana, Switzerland. FAU - Baird, Janis AU - Baird J AD - MRC Lifecourse Epidemiology Unit, University of Southampton, Southampton General Hospital, Tremona Road, Southampton, SO16 6YD, UK. FAU - Dennison, Elaine AU - Dennison E AD - MRC Lifecourse Epidemiology Unit, University of Southampton, Southampton General Hospital, Tremona Road, Southampton, SO16 6YD, UK. FAU - Reginster, Jean-Yves AU - Reginster JY AUID- ORCID: 0000-0001-6290-752X AD - Department of Public Health, Epidemiology and Health Economics, University of Liege, Liege, Belgium. AD - WHO Collaborating Centre for Public Heath Aspects of Musculoskeletal Health and Aging, Liege, Belgium. AD - Biochemistry Department, College of Science, King Saud University, Riyadh, Kingdom of Saudi Arabia. FAU - Cooper, Cyrus AU - Cooper C AUID- ORCID: 0000-0003-3510-0709 AD - MRC Lifecourse Epidemiology Unit, University of Southampton, Southampton General Hospital, Tremona Road, Southampton, SO16 6YD, UK. cc@mrc.soton.ac.uk. AD - WHO Collaborating Centre for Public Heath Aspects of Musculoskeletal Health and Aging, Liege, Belgium. cc@mrc.soton.ac.uk. AD - National Institute for Health Research (NIHR) Musculoskeletal Biomedical Research Unit, University of Oxford, Oxford, UK. cc@mrc.soton.ac.uk. LA - eng GR - 21231/VAC_/Versus Arthritis/United Kingdom GR - MC_U147585819/MRC_/Medical Research Council/United Kingdom GR - MC_UP_A620_1014/MRC_/Medical Research Council/United Kingdom GR - MC_UP_A620_1017/MRC_/Medical Research Council/United Kingdom GR - 19583/VAC_/Versus Arthritis/United Kingdom GR - MC_UU_12011/4/MRC_/Medical Research Council/United Kingdom GR - G0400491/MRC_/Medical Research Council/United Kingdom GR - MC_U147585824/MRC_/Medical Research Council/United Kingdom GR - 10/33/04/DH_/Department of Health/United Kingdom GR - MC_UU_12011/1/MRC_/Medical Research Council/United Kingdom PT - Journal Article PT - Meta-Analysis PT - Research Support, Non-U.S. Gov't PT - Systematic Review PL - New Zealand TA - Drugs Aging JT - Drugs & aging JID - 9102074 RN - 0 (Analgesics, Opioid) RN - 0 (Delayed-Action Preparations) SB - IM MH - Analgesics, Opioid/administration & dosage/*adverse effects/therapeutic use MH - Delayed-Action Preparations MH - Drug-Related Side Effects and Adverse Reactions/epidemiology/*etiology MH - Humans MH - Osteoarthritis/*drug therapy MH - Randomized Controlled Trials as Topic MH - Treatment Outcome PMC - PMC6509215 COIS- Olivier Bruyere reports grants from Biophytis, IBSA, MEDA, Servier, SMB and Theramex, outside of the submitted work. Cyrus Cooper reports personal fees from Alliance for Better Bone Health, Amgen, Eli Lilly, GlaxoSmithKline, Medtronic, Merck, Novartis, Pfizer, Roche, Servier, Takeda and UCB, outside of the submitted work. Jean-Yves Reginster reports grants from IBSA-Genevrier, Mylan, CNIEL and Radius Health (through institution); consulting fees from IBSA-Genevrier, Mylan, CNIEL, Radius Health and Pierre Fabre; fees for participation in review activities from IBSA-Genevrier, MYLAN, CNIEL, Radius Health and Teva; and payment for lectures from AgNovos, CERIN, CNIEL, Dairy Research Council (DRC), Echolight, IBSA-Genevrier, Mylan, Pfizer Consumer Health, Teva and Theramex, outside of the submitted work. Elizabeth Curtis reports lecture fees and travel support from Eli Lilly, Pfizer and UCB, outside of the submitted work. Nicholas Fuggle reports travel support from Eli Lilly and Pfizer, outside of the submitted work. Elaine Dennison reports personal fees for lectures or advisory boards from UCB and Pfizer, outside of the submitted work. Nadia Corp reports partial funding of employment at Keele University from Versus Arthritis (registered charity), as well as travel support from Versus Arthritis, outside of the submitted work. Philip G. Conaghan reports consultancy fees or speakers' bureau fees from Abbvie, BMS, Flexion Therapeutics, GlaxoSmithKline, Merck Serono, Novartis, Pfizer, Roche and Samumed, outside of the submitted work. Germain Honvo, Daniel Uebelhart, Sarah Shaw, Laura Spooner, Georgia Ntani, Camille Parsons and Janis Baird have no discloses to report. EDAT- 2019/05/11 06:00 MHDA- 2019/07/10 06:00 PMCR- 2019/05/09 CRDT- 2019/05/11 06:00 PHST- 2019/05/11 06:00 [entrez] PHST- 2019/05/11 06:00 [pubmed] PHST- 2019/07/10 06:00 [medline] PHST- 2019/05/09 00:00 [pmc-release] AID - 10.1007/s40266-019-00666-9 [pii] AID - 666 [pii] AID - 10.1007/s40266-019-00666-9 [doi] PST - ppublish SO - Drugs Aging. 2019 Apr;36(Suppl 1):129-143. doi: 10.1007/s40266-019-00666-9.