Safety of opioids in osteoarthritis: outcomes of a systematic review and meta-analysis.

[en] 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 metaanalysis. 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 fourto 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.

Disciplines :

Public health, health care sciences & services
General & internal medicine

Author, co-author :

FUGGLE, N

Curtis, E.

Shaw, S.

Spooner, L.

Bruyère, Olivier ; Université de Liège - ULiège > Département des sciences de la santé publique > Santé publique, Epidémiologie et Economie de la santé

Ntani, G.

Parsons, C.

Conaghan, P.G.

Corp, N.

Honvo, Germain ; Université de Liège - ULiège > Département des sciences de la santé publique > Epidémiologie clinique

More authors (5 more)

Language :

English

Title :

Safety of opioids in osteoarthritis: outcomes of a systematic review and meta-analysis.

Publication date :

2019

Journal title :

Drugs and Aging

ISSN :

1170-229X

eISSN :

1179-1969

Publisher :

Adis International, United Kingdom

Volume :

Issue :

suppl 1

Pages :

129-143

Peer reviewed :

Peer Reviewed verified by ORBi

Available on ORBi :

since 15 May 2019

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Bibliography

Pereira D, Peleteiro B, Araujo J, Branco J, Santos RA, Ramos E. The effect of osteoarthritis definition on prevalence and incidence estimates: a systematic review. Osteoarthritis Cartil. 2011;19(11):1270–85.
Vos T, Flaxman AD, Naghavi M, Lozano R, Michaud C, Ezzati M, et al. Years lived with disability (YLDs) for 1160 sequelae of 289 diseases and injuries 1990–2010: a systematic analysis for the Global Burden of Disease Study 2010. Lancet. 2012;380(9859):2163–96.
Lane NE, Brandt K, Hawker G, Peeva E, Schreyer E, Tsuji W, et al. OARSI-FDA initiative: defining the disease state of osteoarthritis. Osteoarthritis Cartil. 2011;19(5):478–82.
Stein C, Pfluger M, Yassouridis A, Hoelzl J, Lehrberger K, Welte C, et al. No tolerance to peripheral morphine analgesia in presence of opioid expression in inflamed synovia. J Clin Invest. 1996;98(3):793–9.
Thorlund JB, Turkiewicz A, Prieto-Alhambra D, Englund M. Opioid use in knee or hip osteoarthritis: a region-wide population-based cohort study. Osteoarthritis Cartilage. Epub 22 Jan 2019. 10.1016/j.joca.2019.01.005.
Desai RJ, Jin Y, Franklin PD, Lee YC, Bateman BT, Lii J et al. Association of geography and access to healthcare providers with long term prescription opioid use in Medicare patients with severe osteoarthritis: A cohort study. Arthritis Rheumatol. Epub 28 Jan 2019. 10.1002/art.40834.
da Costa BR, Nuesch E, Kasteler R, Husni E, Welch V, Rutjes AW et al. Oral or transdermal opioids for osteoarthritis of the knee or hip. Cochrane Database Syst Rev. 2014;9:CD003115.
Avouac J, Gossec L, Dougados M. Efficacy and safety of opioids for osteoarthritis: a meta-analysis of randomized controlled trials. Osteoarthritis Cartil. 2007;15(8):957–65.
Kalso E, Edwards JE, Moore RA, McQuay HJ. Opioids in chronic non-cancer pain: systematic review of efficacy and safety. Pain. 2004;112(3):372–80.
McAlindon TE, Bannuru RR, Sullivan MC, Arden NK, Berenbaum F, Bierma-Zeinstra SM, et al. OARSI guidelines for the non-surgical management of knee osteoarthritis. Osteoarthritis Cartil. 2014;22(3):363–88.
Bruyere O, Cooper C, Pelletier JP, Branco J, Brandi ML, Guillemin F, et al. An algorithm recommendation for the management of knee osteoarthritis in Europe and internationally: a report from a task force of the European Society for Clinical and Economic Aspects of Osteoporosis and Osteoarthritis (ESCEO). Semin Arthritis Rheum. 2014;44(3):253–63.
Bruyere O, Cooper C, Pelletier J-P, Maheu E, Rannou F, Branco J, et al. A consensus statement on the European Society for Clinical and Economic Aspects of Osteoporosis and Osteoarthritis (ESCEO) algorithm for the management of knee osteoarthritis—from evidence-based medicine to the real-life setting. Semin Arthritis Rheum. 2016;45(Suppl 4S):S3–11.
Hochberg MC, Altman RD, April KT, Benkhalti M, Guyatt G, McGowan J, et al. American College of Rheumatology 2012 recommendations for the use of nonpharmacologic and pharmacologic therapies in osteoarthritis of the hand, hip, and knee. Arthritis Care Res. 2012;64(4):465–74.
Nuesch E, Rutjes AW, Husni E, Welch V, Juni P. Oral or transdermal opioids for osteoarthritis of the knee or hip. Cochrane Database Syst Rev. 2009;4:CD003115.
Cepeda MS, Camargo F, Zea C, Valencia L. Tramadol for osteoarthritis. Cochrane Database Syst Rev. 2006;3:CD005522.
Gehling M, Hermann B, Tryba M. Meta-analysis of dropout rates in randomized controlled clinical trials: opioid analgesia for osteoarthritis pain. Schmerz. 2011;25(3):296–305.
Megale RZ, Deveza LA, Blyth FM, Naganathan V, Ferreira PH, McLachlan AJ, et al. Efficacy and safety of oral and transdermal opioid analgesics for musculoskeletal pain in older adults: a systematic review of randomized. Placebo-controlled trials. J Pain. 2018;19(5):475.e1–24.
Cnota PJ, Nowak H, Tagarro I, Erb K, Schurer M, Schulz HU, et al. Tramadol SR formulations: pharmacokinetic comparison of a multiple-units dose (capsule) versus a single-unit dose (tablet). Clin Drug Investig. 2005;25(7):435–43.
Santos J, Alarcao J, Fareleira F, Vaz-Carneiro A, Costa J. Tapentadol for chronic musculoskeletal pain in adults. Cochrane Database Syst Rev. 2015;5:CD009923.
Higgins JPT, Green S. Cochrane handbook for systematic reviews of interventions. Version 5.1.0 (updated March 2011). The Cochrane Collaboration; 2011. http://www.handbook.cochrane.org. Accessed 12 Feb 2019.
Moher D, Liberati A, Tetzlaff J, Altman DG; PRISMA Group. Preferred reporting items for systematic reviews and meta-analyses: the PRISMA statement. J Clin Epidemiol. 2009;62(10):1006–12.
DerSimonian R, Laird N. Meta-analysis in clinical trials. Control Clin Trials. 1986;7(3):177–88.
Bradburn MJ, Deeks JJ, Berlin JA, Russell Localio A. Much ado about nothing: a comparison of the performance of meta-analytical methods with rare events. Stat Med. 2007;26(1):53–77.
Stijnen T, Hamza TH, Ozdemir P. Random effects meta-analysis of event outcome in the framework of the generalized linear mixed model with applications in sparse data. Stat Med. 2010;29(29):3046–67.
Normand SL. Meta-analysis: formulating, evaluating, combining, and reporting. Stat Med. 1999;18(3):321–59.
Higgins JP, Thompson SG, Deeks JJ, Altman DG. Measuring inconsistency in meta-analyses. BMJ. 2003;327(7414):557–60.
Guyatt G, Oxman AD, Akl EA, Kunz R, Vist G, Brozek J et al. GRADE guidelines: 1. Introduction-GRADE evidence profiles and summary of findings tables. J Clin Epidemiol. 2011;64(4):383–94.
GRADEpro GDT: GRADEpro Guideline Development Tool [software]. McMaster University, 2015 (developed by Evidence Prime, Inc.). https://gradepro.org (Evidence Prime, Inc.). Accessed 12 Feb 2019.
Afilalo M, Etropolski MS, Kuperwasser B, Kelly K, Okamoto A, Van Hove I, et al. Efficacy and safety of Tapentadol extended release compared with oxycodone controlled release for the management of moderate to severe chronic pain related to osteoarthritis of the knee: a randomized, double-blind, placebo- and active-controlled phase III study. Clin Drug Investig. 2010;30(8):489–505.
Burch F, Fishman R, Messina N, Corser B, Radulescu F, Sarbu A, et al. A comparison of the analgesic efficacy of Tramadol Contramid OAD versus placebo in patients with pain due to osteoarthritis. J Pain Symptom Manage. 2007;34(3):328–38.
DeLemos BP, Xiang J, Benson C, Gana TJ, Pascual ML, Rosanna R, et al. Tramadol hydrochloride extended-release once-daily in the treatment of osteoarthritis of the knee and/or hip: a double-blind, randomized, dose-ranging trial. Am J Ther. 2011;18(3):216–26.
Fishman RL, Kistler CJ, Ellerbusch MT, Aparicio RT, Swami SS, Shirley ME, et al. Efficacy and safety of 12 weeks of osteoarthritic pain therapy with once-daily tramadol (Tramadol Contramid OAD). J Opioid Manag. 2007;3(5):273–80.
Fleischmann RM, Caldwell JR, Roth SH, Tesser JRP, Olson W, Kamin M. Tramadol for the treatment of joint pain associated with osteoarthritis: a randomized, double-blind, placebo-controlled trial. Curr Ther Res. 2001;62:113–28.
Friedmann N, Klutzaritz V, Webster L. Efficacy and safety of an extended-release oxycodone (Remoxy) formulation in patients with moderate to severe osteoarthritic pain. J Opioid Manag. 2011;7(3):193–202.
Gana TJ, Pascual ML, Fleming RR, Schein JR, Janagap CC, Xiang J, et al. Extended-release tramadol in the treatment of osteoarthritis: a multicenter, randomized, double-blind, placebo-controlled clinical trial. Curr Med Res Opin. 2006;22(7):1391–401.
Hale ME, Laudadio C, Yang R, Narayana A, Malamut R. Efficacy and tolerability of a hydrocodone extended-release tablet formulated with abuse-deterrence technology for the treatment of moderate-to-severe chronic pain in patients with osteoarthritis or low back pain. J Pain Res. 2015;8:623–36.
Hartrick C, Van Hove I, Stegmann JU, Oh C, Upmalis D. Efficacy and tolerability of tapentadol immediate release and oxycodone HCl immediate release in patients awaiting primary joint replacement surgery for end-stage joint disease: a 10-day, phase III, randomized, double-blind, active- and placebo-controlled study. Clin Ther. 2009;31(2):260–71.
Malonne H, Coffiner M, Sonet B, Sereno A, Vanderbist F. Efficacy and tolerability of sustained-release tramadol in the treatment of symptomatic osteoarthritis of the hip or knee: a multicenter, randomized, double-blind, placebo-controlled study. Clin Ther. 2004;26(11):1774–82.
Markenson JA, Croft J, Zhang PG, Richards P. Treatment of persistent pain associated with osteoarthritis with controlled-release oxycodone tablets in a randomized controlled clinical trial. Clin J Pain. 2005;21(6):524–35.
Matsumoto AK, Babul N, Ahdieh H. Oxymorphone extended-release tablets relieve moderate to severe pain and improve physical function in osteoarthritis: results of a randomized, double-blind, placebo- and active-controlled phase III trial. Pain Med. 2005;6(5):357–66.
Rauck R, Rapoport R, Thipphawong J. Results of a double-blind, placebo-controlled, fixed-dose assessment of once-daily OROS(R) hydromorphone ER in patients with moderate to severe pain associated with chronic osteoarthritis. Pain Pract. 2013;13(1):18–29.
Roth SH. Efficacy and safety of tramadol HCl in breakthrough musculoskeletal pain attributed to osteoarthritis. J Rheumatol. 1998;25(7):1358–63.
Spierings EL, Fidelholtz J, Wolfram G, Smith MD, Brown MT, West CR. A phase III placebo- and oxycodone-controlled study of tanezumab in adults with osteoarthritis pain of the hip or knee. Pain. 2013;154(9):1603–12.
Vojtassak J, Vojtassak J, Jacobs A, Rynn L, Waechter S, Richarz U. A phase IIIb, multicentre, randomised, parallel-group, placebo-controlled, double-blind study to investigate the efficacy and safety of OROS hydromorphone in subjects with moderate-to-severe chronic pain induced by osteoarthritis of the hip or the knee. Pain Res Treat. 2011;2011:239501.
Vorsanger G, Xiang J, Jordan D, Farrell J. Post hoc analysis of a randomized, double-blind, placebo-controlled efficacy and tolerability study of tramadol extended release for the treatment of osteoarthritis pain in geriatric patients. Clin Ther. 2007;29(Suppl):2520–35.
Grond S, Sablotzki A. Clinical pharmacology of tramadol. Clin Pharmacokinet. 2004;43(13):879–923.
Tagarro I, Herrera J, Barutell C, Diez MC, Marin M, Samper D, et al. Effect of a simple dose-escalation schedule on tramadol tolerability: assessment in the clinical setting. Clin Drug Investig. 2005;25(1):23–31.
Singh DR, Nag K, Shetti AN, Krishnaveni N. Tapentadol hydrochloride: a novel analgesic. Saudi J Anaesth. 2013;7(3):322–6.
Raffa RB, Buschmann H, Christoph T, Eichenbaum G, Englberger W, Flores CM, et al. Mechanistic and functional differentiation of tapentadol and tramadol. Expert Opin Pharmacother. 2012;13(10):1437–49.