Comparative efficacy and safety of acetaminophen, topical and oral non-steroidal anti-inflammatory drugs for knee osteoarthritis: evidence from a network meta-analysis of randomized controlled trials and real-world data

C Zeng¹, M Doherty², M S M Persson², Z Yang³, A Sarmanova⁴, Y Zhang⁵, J Wei⁶, J Kaur², X Li⁷, G Lei⁸, W Zhang⁹

Affiliations

¹ Department of Orthopaedics, Xiangya Hospital, Central South University, Changsha, China; Division of Rheumatology, Allergy, and Immunology, Department of Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, USA; The Mongan Institute, Massachusetts General Hospital, Harvard Medical School, Boston, USA.
² Academic Rheumatology, Clinical Sciences Building, University of Nottingham, City Hospital, Nottingham, UK; Arthritis Research UK Pain Centre, Nottingham, UK.
³ Department of Epidemiology and Health Statistics, Xiangya School of Public Health, Central South University, Changsha, China.
⁴ Musculoskeletal Research Unit, Bristol Medical School, University of Bristol, Bristol, UK.
⁵ Division of Rheumatology, Allergy, and Immunology, Department of Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, USA; The Mongan Institute, Massachusetts General Hospital, Harvard Medical School, Boston, USA.
⁶ Division of Rheumatology, Allergy, and Immunology, Department of Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, USA; The Mongan Institute, Massachusetts General Hospital, Harvard Medical School, Boston, USA; Health Management Center, Xiangya Hospital, Central South University, Changsha, China.
⁷ Hunan Key Laboratory of Joint Degeneration and Injury, Changsha, China.
⁸ Department of Orthopaedics, Xiangya Hospital, Central South University, Changsha, China; Hunan Key Laboratory of Joint Degeneration and Injury, Changsha, China; Hunan Engineering Research Center of Osteoarthritis, Changsha, China; National Clinical Research Center of Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, China. Electronic address: lei_guanghua@csu.edu.cn.
⁹ Academic Rheumatology, Clinical Sciences Building, University of Nottingham, City Hospital, Nottingham, UK; Arthritis Research UK Pain Centre, Nottingham, UK. Electronic address: weiya.zhang@nottingham.ac.uk.

PMID: 34174454
DOI: 10.1016/j.joca.2021.06.004

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Comparative Study

Comparative efficacy and safety of acetaminophen, topical and oral non-steroidal anti-inflammatory drugs for knee osteoarthritis: evidence from a network meta-analysis of randomized controlled trials and real-world data

C Zeng et al. Osteoarthritis Cartilage. 2021 Sep.

Free article

. 2021 Sep;29(9):1242-1251.

doi: 10.1016/j.joca.2021.06.004. Epub 2021 Jun 24.

Authors

C Zeng¹, M Doherty², M S M Persson², Z Yang³, A Sarmanova⁴, Y Zhang⁵, J Wei⁶, J Kaur², X Li⁷, G Lei⁸, W Zhang⁹

Affiliations

¹ Department of Orthopaedics, Xiangya Hospital, Central South University, Changsha, China; Division of Rheumatology, Allergy, and Immunology, Department of Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, USA; The Mongan Institute, Massachusetts General Hospital, Harvard Medical School, Boston, USA.
² Academic Rheumatology, Clinical Sciences Building, University of Nottingham, City Hospital, Nottingham, UK; Arthritis Research UK Pain Centre, Nottingham, UK.
³ Department of Epidemiology and Health Statistics, Xiangya School of Public Health, Central South University, Changsha, China.
⁴ Musculoskeletal Research Unit, Bristol Medical School, University of Bristol, Bristol, UK.
⁵ Division of Rheumatology, Allergy, and Immunology, Department of Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, USA; The Mongan Institute, Massachusetts General Hospital, Harvard Medical School, Boston, USA.
⁶ Division of Rheumatology, Allergy, and Immunology, Department of Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, USA; The Mongan Institute, Massachusetts General Hospital, Harvard Medical School, Boston, USA; Health Management Center, Xiangya Hospital, Central South University, Changsha, China.
⁷ Hunan Key Laboratory of Joint Degeneration and Injury, Changsha, China.
⁸ Department of Orthopaedics, Xiangya Hospital, Central South University, Changsha, China; Hunan Key Laboratory of Joint Degeneration and Injury, Changsha, China; Hunan Engineering Research Center of Osteoarthritis, Changsha, China; National Clinical Research Center of Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, China. Electronic address: lei_guanghua@csu.edu.cn.
⁹ Academic Rheumatology, Clinical Sciences Building, University of Nottingham, City Hospital, Nottingham, UK; Arthritis Research UK Pain Centre, Nottingham, UK. Electronic address: weiya.zhang@nottingham.ac.uk.

PMID: 34174454
DOI: 10.1016/j.joca.2021.06.004

Abstract

Objective: Current global guidelines regarding the first-line analgesics (acetaminophen, topical or oral non-steroidal anti-inflammatory drugs [NSAIDs]) for knee osteoarthritis remain controversial and their comparative risk-benefit profiles have yet to be adequately assessed.

Design: Pubmed, Embase, Cochrane Library, and Web of Science were searched from database inception to March 2021 for randomized controlled trials (RCTs) comparing acetaminophen, topical NSAIDs and oral NSAIDs directly or indirectly in knee osteoarthritis. Bayesian network meta-analyses were conducted. A propensity-score matched cohort study was also conducted among patients with knee osteoarthritis in The Health Improvement Network database.

Results: 122 RCTs (47,113 participants) were networked. Topical NSAIDs were superior to acetaminophen (standardized mean difference [SMD] = -0.29, 95% credible interval [CrI]: -0.52 to -0.06) and not statistically different from oral NSAIDs (SMD = 0.03, 95% CrI: -0.16 to 0.22) for function. It had lower risk of gastrointestinal adverse effects (AEs) than acetaminophen (risk ratio [RR] = 0.52, 95%CrI: 0.35 to 0.76) and oral NSAIDs (RR = 0.46, 95%CrI: 0.34 to 0.61) in RCTs. In real-world data, topical NSAIDs showed lower risks of all-cause mortality (hazard ratio [HR] = 0.59, 95% confidence interval [CI]: 0.52 to 0.68), cardiovascular diseases (HR = 0.73, 95%CI: 0.63 to 0.85) and gastrointestinal bleeding (HR = 0.53, 95%CI: 0.41 to 0.69) than acetaminophen during the one-year follow-up (n = 22,158 participants/group). A better safety profile was also observed for topical than oral NSAIDs (n = 14,218 participants/group).

Conclusions: Topical NSAIDs are more effective than acetaminophen but not oral NSAIDs for function improvement in people with knee osteoarthritis. Topical NSAIDs are safer than acetaminophen or oral NSAIDs in trials and real-world data.

Keywords: Acetaminophen; Cohort; Meta-analysis; NSAIDs; Oral; Osteoarthritis; Topical.

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Are topical non-steroidal anti-inflammatory drugs (NSAIDs) safer than oral NSAIDs? Or are the adverse effects of topical NSAIDs comparable to those of oral NSAIDs?
Toda K. Toda K. Osteoarthritis Cartilage. 2021 Nov;29(11):1624-1625. doi: 10.1016/j.joca.2021.08.010. Epub 2021 Sep 14. Osteoarthritis Cartilage. 2021. PMID: 34506943 No abstract available.

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Comparative efficacy and safety of acetaminophen, topical and oral non-steroidal anti-inflammatory drugs for knee osteoarthritis: evidence from a network meta-analysis of randomized controlled trials and real-world data

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Comparative efficacy and safety of acetaminophen, topical and oral non-steroidal anti-inflammatory drugs for knee osteoarthritis: evidence from a network meta-analysis of randomized controlled trials and real-world data

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