Comparing the incidence of adverse events following topical versus oral non-steroidal anti-inflammatory drugs for knee osteoarthritis: a systematic review and meta-analysis
DOI:
https://doi.org/10.18203/2394-6040.ijcmph20243449Keywords:
Knee osteoarthritis, NSAIDs, Topical NSAIDs, Oral NSAIDs, Adverse events, Meta-analysisAbstract
Knee osteoarthritis is a prevalent condition that significantly impairs the quality of life, often managed with non-steroidal anti-inflammatory drugs (NSAIDs). While oral NSAIDs are widely used for their systemic effects, they are associated with a higher risk of adverse events (AEs). Topical NSAIDs offer localized approach with potentially fewer systemic side effects, making them an alternative. This meta-analysis compared the incidence of overall AEs associated with topical versus oral NSAIDs in patients with knee osteoarthritis. A systematic search was conducted in PubMed, Cochrane Library, and Embase for studies comparing AEs in patients with knee osteoarthritis treated with topical versus oral NSAIDs. Eight studies with a total of 2,181 participants were included. The pooled odds ratio (OR) for overall AEs was calculated, and heterogeneity among studies was assessed using I² statistic. Publication bias was evaluated using a funnel plot. The meta-analysis demonstrated that topical NSAIDs were associated with lower incidence of AEs compared to oral NSAIDs, with a pooled OR of 0.62 (95% CI: 0.38 to 1.00). This suggests that patients treated with topical NSAIDs were 38% less likely to experience AEs than those treated with oral NSAIDs (p=0.05). Significant heterogeneity was observed among the studies (I²=80%). The funnel plot indicated potential publication bias. Topical NSAIDs offer safer alternative to oral NSAIDs for managing knee osteoarthritis, particularly in reducing the risk of AEs. While the findings are promising, the high degree of heterogeneity and potential publication bias underscore the need for further research to confirm these results.
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References
Sharma L. Osteoarthritis of the knee. N Engl J Med. 2021;384(1):51-9.
Katz JN, Arant KR, Loeser RF. Diagnosis and treatment of hip and knee osteoarthritis: a review. JAMA. 2021;325(6):568-78.
Primorac D, Molnar V, Rod E, Jeleč Ž, Čukelj F, Matišić V, et al. Knee osteoarthritis: a review of pathogenesis and state-of-the-art non-operative therapeutic considerations. Genes. 2020;11(8):854.
Driban JB, Harkey MS, Barbe MF, Ward RJ, MacKay JW, Davis JE, et al. Risk factors and the natural history of accelerated knee osteoarthritis: a narrative review. BMC Musculoskelet Disord. 2020;21:1.
Horecka A, Hordyjewska A, Blicharski T, Kurzepa J. Osteoarthritis of the knee—Biochemical aspect of applied therapies: A review. Bosnian J Basic Med Sci. 2022;22(4):488.
Magni A, Agostoni P, Bonezzi C, Massazza G, Menè P, Savarino V, et al. Management of osteoarthritis: expert opinion on NSAIDs. Pain Ther. 2021;10(2):783-808.
Vincent TL. Peripheral pain mechanisms in osteoarthritis. Pain. 2020;161:S138-46.
Bariguian Revel F, Fayet M, Hagen M. Topical diclofenac, an efficacious treatment for osteoarthritis: a narrative review. Rheumatol Ther. 2020;7(2):217-36.
Richard MJ, Driban JB, McAlindon TE. Pharmaceutical treatment of osteoarthritis. Osteoarthr Cartil. 2023;31(4):458-66.
Richard MJ, Driban JB, McAlindon TE. Pharmaceutical treatment of osteoarthritis. Osteoarthr Cartil. 2023;31(4):458-66.
Lee JK, Abbas AA, Cheah TE, Simanjuntak RN, Sockalingam S, Roohi S. Topical nonsteroidal anti‐inflammatory drugs for management of osteoarthritis pain: A consensus recommendation. J Orthop Res. 2023;41(9):1916-24.
Cao P, Li Y, Tang Y, Ding C, Hunter DJ. Pharmacotherapy for knee osteoarthritis: current and emerging therapies. Exp Opinion Pharmacother. 2020;21(7):797-809.
Page MJ, McKenzie JE, Bossuyt PM, Boutron I, Hoffmann TC, Mulrow CD, et al. Updating guidance for reporting systematic reviews: development of the PRISMA 2020 statement. J Clin Epidemiol. 2021;134:103-12.
Tugwell PS, Wells GA, Shainhouse JZ. Equivalence study of a topical diclofenac solution (pennsaid) compared with oral diclofenac in symptomatic treatment of osteoarthritis of the knee: a randomized controlled trial. J Rheumatol. 2004;31(10):2002-12.
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.
Underwood M, Ashby D, Cross P, Hennessy E, Letley L, Martin J, et al. Advice to use topical or oral ibuprofen for chronic knee pain in older people: randomised controlled trial and patient preference study. BMJ. 2008;336(7636):138-42.
Simon LS, Grierson LM, Naseer Z, Bookman AA, Zev Shainhouse J. Efficacy and safety of topical diclofenac containing dimethyl sulfoxide (DMSO) compared with those of topical placebo, DMSO vehicle and oral diclofenac for knee osteoarthritis. Pain. 2009;143(3):238-45.
Tiso RL, Tong-Ngork S, Fredlund KL. Oral versus topical Ibuprofen for chronic knee pain: a prospective randomized pilot study. Pain Physician. 2010;13(5):457.
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.
Mu R, Bao CD, Chen ZW, Zheng Y, Wang GC, Zhao DB, et al. Efficacy and safety of loxoprofen hydrogel patch versus loxoprofen tablet in patients with knee osteoarthritis: a randomized controlled non-inferiority trial. Clin Rheumatol. 2016;35:165-73.
Shinde VA, Kalikar M, Jagtap S, Dakhale GN, Bankar M, Bajait CS, et al. Efficacy and safety of oral diclofenac sustained release versus transdermal diclofenac patch in chronic musculoskeletal pain: a randomized, open label trial. J Pharmacol Pharmacother. 2017;8(4):166-71.
Page MJ, Sterne JA, Higgins JP, Egger M. Investigating and dealing with publication bias and other reporting biases in meta‐analyses of health research: A review. Res Synthesis Method. 2021;12(2):248-59.
Doleman B, Freeman SC, Lund JN, Williams JP, Sutton AJ. Funnel plots may show asymmetry in the absence of publication bias with continuous outcomes dependent on baseline risk: presentation of a new publication bias test. Res Synthesis Method. 2020;11(4):522-34.