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Open Access 01-04-2019 | Osteoarthrosis | Systematic Review

Safety of Cyclooxygenase-2 Inhibitors in Osteoarthritis: Outcomes of a Systematic Review and Meta-Analysis

Authors: Elizabeth Curtis, Nicholas Fuggle, Sarah Shaw, Laura Spooner, Georgia Ntani, Camille Parsons, Nadia Corp, Germain Honvo, Janis Baird, Stefania Maggi, Elaine Dennison, Olivier Bruyère, Jean-Yves Reginster, Cyrus Cooper

Published in: Drugs & Aging | Special Issue 1/2019

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; I² = 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; I² = 0%), particularly for abdominal pain, which increased by 40% with COX-2 inhibitors (RR 1.40, 95% CI 1.08–1.80; I² = 0%). The risk of hypertension increased by 45% overall (RR 1.45, 95% CI 1.01–2.10; I² = 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; I² = 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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Harirforoosh S, Asghar W, Jamali F. Adverse effects of nonsteroidal antiinflammatory drugs: an update of gastrointestinal, cardiovascular and renal complications. J Pharm Pharm Sci. 2013;16(5):821–47.CrossRefPubMed

Donnelly MT, Hawkey CJ. Review article: COX-II inhibitors—a new generation of safer NSAIDs? Aliment Pharmacol Ther. 1997;11(2):227–36.CrossRefPubMed

Bresalier RS, Sandler RS, Quan H, Bolognese JA, Oxenius B, Horgan K, et al. Cardiovascular events associated with rofecoxib in a colorectal adenoma chemoprevention trial. N Engl J Med. 2005;352(11):1092–102. https://doi.org/10.1056/NEJMoa050493.CrossRefPubMed

Ott E, Nussmeier NA, Duke PC, Feneck RO, Alston RP, Snabes MC, et al. Efficacy and safety of the cyclooxygenase 2 inhibitors parecoxib and valdecoxib in patients undergoing coronary artery bypass surgery. J Thorac Cardiovasc Surg. 2003;125(6):1481–92.CrossRefPubMed

Nussmeier NA, Whelton AA, Brown MT, Langford RM, Hoeft A, Parlow JL, et al. Complications of the COX-2 inhibitors parecoxib and valdecoxib after cardiac surgery. N Engl J Med. 2005;352(11):1081–91. https://doi.org/10.1056/NEJMoa050330.CrossRefPubMed

Pillans PI, Ghiculescu RA, Lampe G, Wilson R, Wong R, Macdonald GA. Severe acute liver injury associated with lumiracoxib. J Gastroenterol Hepatol. 2012;27(6):1102–5. https://doi.org/10.1111/j.1440-1746.2011.07036.x.CrossRefPubMed

Patrignani P, Tacconelli S, Bruno A, Sostres C, Lanas A. Managing the adverse effects of nonsteroidal anti-inflammatory drugs. Expert Rev Clin Pharmacol. 2011;4(5):605–21. https://doi.org/10.1586/ecp.11.36.CrossRefPubMed

Yang M, Wang HT, Zhao M, Meng WB, Ou JQ, He JH, et al. Network meta-analysis comparing relatively selective COX-2 inhibitors versus coxibs for the prevention of NSAID-induced gastrointestinal injury. Medicine (Baltimore). 2015;94(40):e1592. https://doi.org/10.1097/MD.0000000000001592.CrossRef

van Walsem A, Pandhi S, Nixon RM, Guyot P, Karabis A, Moore RA. Relative benefit-risk comparing diclofenac to other traditional non-steroidal anti-inflammatory drugs and cyclooxygenase-2 inhibitors in patients with osteoarthritis or rheumatoid arthritis: a network meta-analysis. Arthritis Res Ther. 2015;17:66. https://doi.org/10.1186/s13075-015-0554-0.CrossRefPubMedPubMedCentral

10.

Essex MN, Zhang RY, Berger MF, Upadhyay S, Park PW. Safety of celecoxib compared with placebo and non-selective NSAIDs: cumulative meta-analysis of 89 randomized controlled trials. Expert Opin Drug Saf. 2013;12(4):465–77. https://doi.org/10.1517/14740338.2013.780595.CrossRefPubMed

11.

Coxib and traditional NSAID Trialists’ (CNT) Collaboration, Bhala N, Emberson J, Merhi A, Abramson S, Arber N, et al. Vascular and upper gastrointestinal effects of non-steroidal anti-inflammatory drugs: meta-analyses of individual participant data from randomised trials. Lancet. 2013;382(9894):769–79. https://doi.org/10.1016/s0140-6736(13)60900-9.CrossRef

12.

Trelle S, Reichenbach S, Wandel S, Hildebrand P, Tschannen B, Villiger PM, et al. Cardiovascular safety of non-steroidal anti-inflammatory drugs: network meta-analysis. BMJ. 2011;342:c7086. https://doi.org/10.1136/bmj.c7086.CrossRefPubMedPubMedCentral

13.

Zhang J, Ding EL, Song Y. Adverse effects of cyclooxygenase 2 inhibitors on renal and arrhythmia events: meta-analysis of randomized trials. JAMA. 2006;296(13):1619–32. https://doi.org/10.1001/jama.296.13.jrv60015.CrossRefPubMed

14.

McGettigan P, Henry D. Cardiovascular risk and inhibition of cyclooxygenase: a systematic review of the observational studies of selective and nonselective inhibitors of cyclooxygenase 2. JAMA. 2006;296(13):1633–44. https://doi.org/10.1001/jama.296.13.jrv60011.CrossRefPubMed

15.

Higgins JPT, Green S. Cochrane handbook for systematic reviews of interventions. Version 5.1.0 (updated March 2011). The Cochrane Collaboration. http://www.handbook.cochrane.org.

16.

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. https://doi.org/10.1016/j.jclinepi.2009.06.005.CrossRefPubMed

17.

DerSimonian R, Laird N. Meta-analysis in clinical trials. Control Clin Trials. 1986;7(3):177–88.CrossRefPubMed

18.

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. https://doi.org/10.1002/sim.2528.CrossRefPubMed

19.

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. https://doi.org/10.1002/sim.4040.CrossRefPubMed

20.

Normand SL. Meta-analysis: formulating, evaluating, combining, and reporting. Stat Med. 1999;18(3):321–59.CrossRefPubMed

21.

Higgins JP, Thompson SG, Deeks JJ, Altman DG. Measuring inconsistency in meta-analyses. BMJ. 2003;327(7414):557–60. https://doi.org/10.1136/bmj.327.7414.557.CrossRefPubMedPubMedCentral

22.

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. https://doi.org/10.1016/j.jclinepi.2010.04.026.CrossRefPubMed

23.

GRADEpro GDT. GRADEpro Guideline Development Tool [Software]. McMaster University, 2015 (developed by Evidence Prime, Inc.). Evidence Prime, Inc. http://gradepro.org.

24.

Bensen WG, Fiechtner JJ, McMillen JI, Zhao WW, Yu SS, Woods EM, et al. Treatment of osteoarthritis with celecoxib, a cyclooxygenase-2 inhibitor: a randomized controlled trial. Mayo Clin Proc. 1999;74(11):1095–105. https://doi.org/10.4065/74.11.1095.CrossRefPubMed

25.

Bingham CO 3rd, Sebba AI, Rubin BR, Ruoff GE, Kremer J, Bird S, et al. Efficacy and safety of etoricoxib 30 mg and celecoxib 200 mg in the treatment of osteoarthritis in two identically designed, randomized, placebo-controlled, non-inferiority studies. Rheumatology (Oxford). 2007;46(3):496–507. https://doi.org/10.1093/rheumatology/kel296.CrossRef

26.

Cannon CP, Chen C, Curtis SP, Viscusi J, Ahmed T, Dibattiste PM. A comparison of cardiovascular biomarkers in patients treated for three months with etoricoxib, celecoxib, ibuprofen, and placebo. Arch Drug Inf. 2008;1(1):4–13. https://doi.org/10.1111/j.1753-5174.2007.00002.x.CrossRefPubMedPubMedCentral

27.

Conaghan PG, Dickson J, Bolten W, Cevc G, Rother M. A multicentre, randomized, placebo- and active-controlled trial comparing the efficacy and safety of topical ketoprofen in Transfersome gel (IDEA-033) with ketoprofen-free vehicle (TDT 064) and oral celecoxib for knee pain associated with osteoarthritis. Rheumatology (Oxford). 2013;52(7):1303–12. https://doi.org/10.1093/rheumatology/ket133.CrossRef

28.

Cryer BL, Sostek MB, Fort JG, Svensson O, Hwang C, Hochberg MC. A fixed-dose combination of naproxen and esomeprazole magnesium has comparable upper gastrointestinal tolerability to celecoxib in patients with osteoarthritis of the knee: results from two randomized, parallel-group, placebo-controlled trials. Ann Med. 2011;43(8):594–605. https://doi.org/10.3109/07853890.2011.625971.CrossRefPubMed

29.

Day R, Morrison B, Luza A, Castaneda O, Strusberg A, Nahir M, et al. A randomized trial of the efficacy and tolerability of the COX-2 inhibitor rofecoxib vs ibuprofen in patients with osteoarthritis. Rofecoxib/Ibuprofen Comparator Study Group. Arch Intern Med. 2000;160(12):1781–7.CrossRefPubMed

30.

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. https://doi.org/10.1097/MJT.0b013e3181cec307.CrossRefPubMed

31.

Ehrich EW, Schnitzer TJ, McIlwain H, Levy R, Wolfe F, Weisman M, et al. Effect of specific COX-2 inhibition in osteoarthritis of the knee: a 6 week double blind, placebo controlled pilot study of rofecoxib. Rofecoxib Osteoarthritis Pilot Study Group. J Rheumatol. 1999;26(11):2438–47.PubMed

32.

Essex MN, O’Connell M, Bhadra Brown P. Response to nonsteroidal anti-inflammatory drugs in African Americans with osteoarthritis of the knee. J Int Med Res. 2012;40(6):2251–66. https://doi.org/10.1177/030006051204000623.CrossRefPubMed

33.

Essex MN, Behar R, O’Connell MA, Brown PB. Efficacy and tolerability of celecoxib and naproxen versus placebo in Hispanic patients with knee osteoarthritis. Int J Gen Med. 2014;7:227–35. https://doi.org/10.2147/ijgm.s61297.CrossRefPubMedPubMedCentral

34.

Essex MN, O’Connell MA, Behar R, Bao W. Efficacy and safety of nonsteroidal anti-inflammatory drugs in Asian patients with knee osteoarthritis: summary of a randomized, placebo-controlled study. Int J Rheum Dis. 2016;19(3):262–70. https://doi.org/10.1111/1756-185x.12667.CrossRefPubMed

35.

Fleischmann R, Sheldon E, Maldonado-Cocco J, Dutta D, Yu S, Sloan VS. Lumiracoxib is effective in the treatment of osteoarthritis of the knee: a prospective randomized 13-week study versus placebo and celecoxib. Clin Rheumatol. 2006;25(1):42–53. https://doi.org/10.1007/s10067-005-1126-5.CrossRefPubMed

36.

Ghosh S, Paul S, Das N, Bhattacharyya TK. A study on the effects of diclofenac sodium and etoricoxib in the treatment of osteoarthritis. J Indian Med Assoc. 2007;105(5):260–2.PubMed

37.

Gordo AC, Walker C, Armada B, Zhou D. Efficacy of celecoxib versus ibuprofen for the treatment of patients with osteoarthritis of the knee: a randomized double-blind, non-inferiority trial. J Int Med Res. 2017;45(1):59–74. https://doi.org/10.1177/0300060516673707.CrossRefPubMedPubMedCentral

38.

Gottesdiener K, Schnitzer T, Fisher C, Bockow B, Markenson J, Ko A, et al. Results of a randomized, dose-ranging trial of etoricoxib in patients with osteoarthritis. Rheumatology (Oxford). 2002;41(9):1052–61.CrossRef

39.

Karlsson J, Pivodic A, Aguirre D, Schnitzer TJ. Efficacy, safety, and tolerability of the cyclooxygenase-inhibiting nitric oxide donator naproxcinod in treating osteoarthritis of the hip or knee. J Rheumatol. 2009;36(6):1290–7. https://doi.org/10.3899/jrheum.081011.CrossRefPubMed

40.

Kivitz AJ, Moskowitz RW, Woods E, Hubbard RC, Verburg KM, Lefkowith JB, et al. Comparative efficacy and safety of celecoxib and naproxen in the treatment of osteoarthritis of the hip. J Int Med Res. 2001;29(6):467–79. https://doi.org/10.1177/147323000102900602.CrossRefPubMed

41.

Laine L, Harper S, Simon T, Bath R, Johanson J, Schwartz H, et al. A randomized trial comparing the effect of rofecoxib, a cyclooxygenase 2-specific inhibitor, with that of ibuprofen on the gastroduodenal mucosa of patients with osteoarthritis. Rofecoxib Osteoarthritis Endoscopy Study Group. Gastroenterology. 1999;117(4):776–83.CrossRefPubMed

42.

Lehmann R, Brzosko M, Kopsa P, Nischik R, Kreisse A, Thurston H, et al. Efficacy and tolerability of lumiracoxib 100 mg once daily in knee osteoarthritis: a 13-week, randomized, double-blind study vs. placebo and celecoxib. Curr Med Res Opin. 2005;21(4):517–26. https://doi.org/10.1185/030079905x38196.CrossRefPubMed

43.

Leung AT, Malmstrom K, Gallacher AE, Sarembock B, Poor G, Beaulieu A, et al. Efficacy and tolerability profile of etoricoxib in patients with osteoarthritis: a randomized, double-blind, placebo and active-comparator controlled 12-week efficacy trial. Curr Med Res Opin. 2002;18(2):49–58. https://doi.org/10.1185/030079902125000282.CrossRefPubMed

44.

McKenna F, Borenstein D, Wendt H, Wallemark C, Lefkowith JB, Geis GS. Celecoxib versus diclofenac in the management of osteoarthritis of the knee. Scand J Rheumatol. 2001;30(1):11–8.CrossRefPubMed

45.

Puopolo A, Boice JA, Fidelholtz JL, Littlejohn TW, Miranda P, Berrocal A, et al. A randomized placebo-controlled trial comparing the efficacy of etoricoxib 30 mg and ibuprofen 2400 mg for the treatment of patients with osteoarthritis. Osteoarthr Cartil. 2007;15(12):1348–56. https://doi.org/10.1016/j.joca.2007.05.022.CrossRef

46.

Reginster JY, Malmstrom K, Mehta A, Bergman G, Ko AT, Curtis SP, et al. Evaluation of the efficacy and safety of etoricoxib compared with naproxen in two, 138-week randomised studies of patients with osteoarthritis. Ann Rheum Dis. 2007;66(7):945–51. https://doi.org/10.1136/ard.2006.059162.CrossRefPubMed

47.

Rother M, Lavins BJ, Kneer W, Lehnhardt K, Seidel EJ, Mazgareanu S. Efficacy and safety of epicutaneous ketoprofen in Transfersome (IDEA-033) versus oral celecoxib and placebo in osteoarthritis of the knee: multicentre randomised controlled trial. Ann Rheum Dis. 2007;66(9):1178–83. https://doi.org/10.1136/ard.2006.065128.CrossRefPubMedPubMedCentral

48.

Saag K, van der Heijde D, Fisher C, Samara A, DeTora L, Bolognese J, et al. Rofecoxib, a new cyclooxygenase 2 inhibitor, shows sustained efficacy, comparable with other nonsteroidal anti-inflammatory drugs: a 6-week and a 1-year trial in patients with osteoarthritis. Osteoarthritis Studies Group. Arch Fam Med. 2000;9(10):1124–34.CrossRefPubMed

49.

Sawitzke AD, Shi H, Finco MF, Dunlop DD, Harris CL, Singer NG, et al. Clinical efficacy and safety of glucosamine, chondroitin sulphate, their combination, celecoxib or placebo taken to treat osteoarthritis of the knee: 2-year results from GAIT. Ann Rheum Dis. 2010;69(8):1459–64. https://doi.org/10.1136/ard.2009.120469.CrossRefPubMed

50.

Schnitzer TJ, Kivitz AJ, Lipetz RS, Sanders N, Hee A. Comparison of the COX-inhibiting nitric oxide donator AZD3582 and rofecoxib in treating the signs and symptoms of Osteoarthritis of the knee. Arthritis Rheumatol. 2005;53(6):827–37. https://doi.org/10.1002/art.21586.CrossRef

51.

Schnitzer TJ, Dattani ID, Seriolo B, Schneider H, Moore A, Tseng L, et al. A 13-week, multicenter, randomized, double-blind study of lumiracoxib in hip osteoarthritis. Clin Rheumatol. 2011;30(11):1433–46. https://doi.org/10.1007/s10067-011-1776-4.CrossRefPubMed

52.

Sheldon E, Beaulieu A, Paster Z, Dutta D, Yu S, Sloan VS. Efficacy and tolerability of lumiracoxib in the treatment of osteoarthritis of the knee: a 13-week, randomized, double-blind comparison with celecoxib and placebo. Clin Ther. 2005;27(1):64–77. https://doi.org/10.1016/j.clinthera.2005.01.002.CrossRefPubMed

53.

Smugar SS, Schnitzer TJ, Weaver AL, Rubin BR, Polis AB, Tershakovec AM. Rofecoxib 12.5 mg, rofecoxib 25 mg, and celecoxib 200 mg in the treatment of symptomatic osteoarthritis: results of two similarly designed studies. Curr Med Res Opin. 2006;22(7):1353–67. https://doi.org/10.1185/030079906x104876.CrossRefPubMed

54.

Tannenbaum H, Berenbaum F, Reginster JY, Zacher J, Robinson J, Poor G, et al. Lumiracoxib is effective in the treatment of osteoarthritis of the knee: a 13 week, randomised, double blind study versus placebo and celecoxib. Ann Rheum Dis. 2004;63(11):1419–26. https://doi.org/10.1136/ard.2003.015974.CrossRefPubMedPubMedCentral

55.

Truitt KE, Sperling RS, Ettinger WH Jr, Greenwald M, DeTora L, Zeng Q, et al. A multicenter, randomized, controlled trial to evaluate the safety profile, tolerability, and efficacy of rofecoxib in advanced elderly patients with osteoarthritis. Aging (Milano). 2001;13(2):112–21.

56.

Weaver AL, Messner RP, Storms WW, Polis AB, Najarian DK, Petruschke RA, et al. Treatment of patients with osteoarthritis with rofecoxib compared with nabumetone. J Clin Rheumatol. 2006;12(1):17–25. https://doi.org/10.1097/01.rhu.0000200384.79405.33.CrossRefPubMed

57.

Wiesenhutter CW, Boice JA, Ko A, Sheldon EA, Murphy FT, Wittmer BA, et al. Evaluation of the comparative efficacy of etoricoxib and ibuprofen for treatment of patients with osteoarthritis: a randomized, double-blind, placebo-controlled trial. Mayo Clin Proc. 2005;80(4):470–9.CrossRefPubMed

58.

Williams GW, Ettlinger RE, Ruderman EM, Hubbard RC, Lonien ME, Yu SS, et al. Treatment of osteoarthritis with a once-daily dosing regimen of celecoxib: a randomized, controlled trial. J Clin Rheumatol. 2000;6(2):65–74.CrossRefPubMed

59.

Mallen SR, Essex MN, Zhang R. Gastrointestinal tolerability of NSAIDs in elderly patients: a pooled analysis of 21 randomized clinical trials with celecoxib and nonselective NSAIDs. Curr Med Res Opin. 2011;27(7):1359–66. https://doi.org/10.1185/03007995.2011.581274.CrossRefPubMed

60.

Sudano I, Flammer AJ, Roas S, Enseleit F, Noll G, Ruschitzka F. Nonsteroidal antiinflammatory drugs, acetaminophen, and hypertension. Curr Hypertens Rep. 2012;14(4):304–9. https://doi.org/10.1007/s11906-012-0274-7.CrossRefPubMed

61.

Sowers JR, White WB, Pitt B, Whelton A, Simon LS, Winer N, et al. The Effects of cyclooxygenase-2 inhibitors and nonsteroidal anti-inflammatory therapy on 24-hour blood pressure in patients with hypertension, osteoarthritis, and type 2 diabetes mellitus. Arch Intern Med. 2005;165(2):161–8. https://doi.org/10.1001/archinte.165.2.161.CrossRefPubMed

62.

Lewington S, Clarke R, Qizilbash N, Peto R, Collins R, Prospective Studies C. Age-specific relevance of usual blood pressure to vascular mortality: a meta-analysis of individual data for one million adults in 61 prospective studies. Lancet. 2002;360(9349):1903–13.CrossRefPubMed

63.

Ungprasert P, Srivali N, Thongprayoon C. Nonsteroidal anti-inflammatory drugs and risk of incident heart failure: a systematic review and meta-analysis of observational studies. Clin Cardiol. 2016;39(2):111–8. https://doi.org/10.1002/clc.22502.CrossRefPubMed

64.

Mamdani M, Juurlink DN, Lee DS, Rochon PA, Kopp A, Naglie G, et al. Cyclo-oxygenase-2 inhibitors versus non-selective non-steroidal anti-inflammatory drugs and congestive heart failure outcomes in elderly patients: a population-based cohort study. Lancet. 2004;363(9423):1751–6. https://doi.org/10.1016/S0140-6736(04)16299-5.CrossRefPubMed

65.

Nissen SE, Yeomans ND, Solomon DH, Luscher TF, Libby P, Husni ME, et al. Cardiovascular safety of celecoxib, naproxen, or ibuprofen for arthritis. N Engl J Med. 2016;375(26):2519–29. https://doi.org/10.1056/NEJMoa1611593.CrossRefPubMed

66.

Solomon DH, Husni ME, Wolski KE, Wisniewski LM, Borer JS, Graham DY, et al. Differences in safety of nonsteroidal antiinflammatory drugs in patients with osteoarthritis and patients with rheumatoid arthritis: a randomized clinical trial. Arthritis Rheumatol. 2018;70(4):537–46. https://doi.org/10.1002/art.40400.CrossRefPubMed

67.

Hirayama A, Tanahashi N, Daida H, Ishiguro N, Chachin M, Sugioka T, et al. Assessing the cardiovascular risk between celecoxib and nonselective nonsteroidal antiinflammatory drugs in patients with rheumatoid arthritis and osteoarthritis. Circ J. 2014;78(1):194–205.CrossRefPubMed

68.

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. https://doi.org/10.1016/j.semarthrit.2014.05.014.CrossRefPubMed

Title: Safety of Cyclooxygenase-2 Inhibitors in Osteoarthritis: Outcomes of a Systematic Review and Meta-Analysis
Authors: Elizabeth Curtis
Nicholas Fuggle
Sarah Shaw
Laura Spooner
Georgia Ntani
Camille Parsons
Nadia Corp
Germain Honvo
Janis Baird
Stefania Maggi
Elaine Dennison
Olivier Bruyère
Jean-Yves Reginster
Cyrus Cooper
Publication date: 01-04-2019
Publisher: Springer International Publishing
Keywords: Osteoarthrosis
Edema
Osteoarthrosis
Celecoxib
Etoricoxib
Heart Failure
Diarrhea
Diarrhea
Key Symptom
Abdominal Pain
Published in: Drugs & Aging / Issue Special Issue 1/2019
Print ISSN: 1170-229X
Electronic ISSN: 1179-1969
DOI: https://doi.org/10.1007/s40266-019-00664-x

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