{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,17]],"date-time":"2026-10-17T23:51:40Z","timestamp":1792281100321,"version":"4.4.0"},"reference-count":34,"publisher":"Oxford University Press (OUP)","issue":"3","license":[{"start":{"date-parts":[[2020,11,3]],"date-time":"2020-11-03T00:00:00Z","timestamp":1604361600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/journals\/pages\/open_access\/funder_policies\/chorus\/standard_publication_model"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2021,3,18]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:sec>\n                  <jats:title>Objectives<\/jats:title>\n                  <jats:p>To evaluate the safety of low-dose tanezumab in the treatment of knee or hip osteoarthritis (OA).<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>Databases were searched up to September 2019 for phase III randomized controlled trials (RCTs). Eleven phase III RCTs comprising 11,455 patients were eligible. The pooled estimates of safety outcomes were assessed and expressed using relative risks (RRs) and 95% confidence intervals with a random-effects model.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>Tanezumab significantly increased the incidence of rapidly progressive OA (RPOA; RR\u2009=\u20099.07, 95% CI = 1.21\u201367.90, P\u2009=\u20090.03) and abnormal peripheral sensation (APS; RR\u2009=\u20092.68, 95% CI = 1.64\u20134.37, P\u2009&amp;lt;\u20090.00001) compared with placebo. No significant difference was found in terms of incidence of total joint replacement (TJR; RR\u2009=\u20091.13, 95% CI = 0.76\u20131.68, P\u2009=\u20090.55) or withdrawal due to adverse effects (AEs; RR\u2009=\u20091.26, 95% CI = 0.79\u20132.00, P\u2009=\u20090.33). The tanezumab group showed a statistically higher incidence of RPOA (RR\u2009=\u20093.96, 95% CI = 2.23\u20137.04, P\u2009&amp;lt;\u20090.00001) and APS (RR\u2009=\u20091.2, 95% CI = 1.44\u20132.56, P\u2009&amp;lt;\u20090.00001) compared with the nonsteroidal anti-inflammatory drugs and opioids group. No significant difference was found in terms of TJR (RR\u2009=\u20091.51, 95% CI = 0.65\u20133.47, P\u2009=\u20090.33) and withdrawal (RR\u2009=\u20090.54, 95% CI = 0.20\u20131.40, P\u2009=\u20090.20). Subgroup analysis revealed that 2.5\u2009mg of tanezumab did not show an advantage over 5\u2009mg of tanezumab in reducing AEs.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusions<\/jats:title>\n                  <jats:p>These results demonstrate that RPOA and APS should be the most concerning AEs when using tanezumab in OA patients. Additional data are needed to define the optimal dose to minimize risk and to determine the optimal subjects to receive this treatment.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1093\/pm\/pnaa260","type":"journal-article","created":{"date-parts":[[2020,7,7]],"date-time":"2020-07-07T19:11:01Z","timestamp":1594149061000},"page":"585-595","source":"Crossref","is-referenced-by-count":13,"title":["Safety of Low-Dose Tanezumab in the Treatment of Hip or Knee Osteoarthritis: A Systemic Review and Meta-analysis of Randomized Phase III Clinical Trials"],"prefix":"10.1093","volume":"22","author":[{"given":"Yang","family":"Yu","sequence":"first","affiliation":[{"name":"Department of Orthopaedics, The First Affiliated Hospital of Zhengzhou University, Zhengzhou University, Zhengzhou, Henan Province, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shi-Tao","family":"Lu","sequence":"additional","affiliation":[{"name":"Department of Orthopaedics, The First Affiliated Hospital of Zhengzhou University, Zhengzhou University, Zhengzhou, Henan Province, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jin-Peng","family":"Sun","sequence":"additional","affiliation":[{"name":"Department of Orthopaedics, The First Affiliated Hospital of Zhengzhou University, Zhengzhou University, Zhengzhou, Henan Province, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wei","family":"Zhou","sequence":"additional","affiliation":[{"name":"Department of Orthopaedics, The First Affiliated Hospital of Zhengzhou University, Zhengzhou University, Zhengzhou, Henan Province, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2020,11,3]]},"reference":[{"issue":"10182","key":"2021031817231993500_pnaa260-B1","doi-asserted-by":"crossref","first-page":"1745","DOI":"10.1016\/S0140-6736(19)30417-9","article-title":"Osteoarthritis","volume":"393","author":"Hunter","year":"2019","journal-title":"Lancet"},{"issue":"2","key":"2021031817231993500_pnaa260-B2","doi-asserted-by":"crossref","first-page":"312","DOI":"10.1016\/j.berh.2018.10.007","article-title":"Update on the epidemiology, risk factors and disease outcomes of osteoarthritis","volume":"32","author":"O'Neill","year":"2018","journal-title":"Best Pract Res Clin Rheumatol"},{"issue":"2","key":"2021031817231993500_pnaa260-B3","doi-asserted-by":"crossref","first-page":"63","DOI":"10.1097\/00045391-200007020-00004","article-title":"Renal and related cardiovascular effects of conventional and COX-2-specific NSAIDs and non-NSAID analgesics","volume":"7","author":"Whelton","year":"2000","journal-title":"Am J Ther"},{"issue":"1","key":"2021031817231993500_pnaa260-B4","doi-asserted-by":"crossref","first-page":"307","DOI":"10.1146\/annurev-neuro-072116-031121","article-title":"Nerve growth factor and pain mechanisms","volume":"40","author":"Denk","year":"2017","journal-title":"Annu Rev Neurosci"},{"issue":"7","key":"2021031817231993500_pnaa260-B5","doi-asserted-by":"crossref","first-page":"2223","DOI":"10.1002\/art.34385","article-title":"Neuroplasticity of sensory and sympathetic nerve fibers in a mouse model of a painful arthritic joint","volume":"64","author":"Ghilardi","year":"2012","journal-title":"Arthritis Rheum"},{"issue":"7","key":"2021031817231993500_pnaa260-B6","doi-asserted-by":"crossref","first-page":"400","DOI":"10.1038\/nrrheum.2013.44","article-title":"Biologic agents in osteoarthritis: Hopes and disappointments","volume":"9","author":"Chevalier","year":"2013","journal-title":"Nat Rev Rheumatol"},{"issue":"2","key":"2021031817231993500_pnaa260-B7","first-page":"374","article-title":"Efficacy and safety of tanezumab on osteoarthritis knee and hip pains: A meta-analysis of randomized controlled trials","volume":"18","author":"Chen","year":"2017","journal-title":"Pain Med"},{"issue":"6","key":"2021031817231993500_pnaa260-B8","doi-asserted-by":"crossref","first-page":"e0157105","DOI":"10.1371\/journal.pone.0157105","article-title":"Tanezumab for patients with osteoarthritis of the knee: A meta-analysis","volume":"11","author":"Kan","year":"2016","journal-title":"PLoS One"},{"key":"2021031817231993500_pnaa260-B9","doi-asserted-by":"crossref","first-page":"S8","DOI":"10.1016\/j.joca.2014.10.003","article-title":"A systematic review of the efficacy and general safety of antibodies to NGF in the treatment of OA of the hip or knee","volume":"23(Suppl 1","author":"Schnitzer","year":"2015","journal-title":"Osteoarthritis Cartilage"},{"issue":"2","key":"2021031817231993500_pnaa260-B10","doi-asserted-by":"crossref","first-page":"382","DOI":"10.1002\/art.39492","article-title":"When is osteonecrosis not osteonecrosis? 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