Subcutaneous tanezumab for osteoarthritis of the hip or knee: efficacy and safety results from a 24-week randomised phase III study with a 24-week follow-up period

Bérenbaum, Francis; Blanco, Francisco J.; Guermazi, Ali; Miki, Kenji; Yamabe, Takaharu; Viktrup, Lars; Junor, Rod; Carey, William; Brown, Mark T.; West, Christine R.; Verburg, Kenneth M.

doi:10.1136/annrheumdis-2019-216296

Cited by 116 publications

(180 citation statements)

References 31 publications

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“…Evidence suggests that NGF is a potential target for controlling OA pain. 4,17 Favorable effects 18,28,29 on relationships between estrogen and OA symptoms have been reported. In this paper, we showed that E2 reduces chondrocytes NGF expression significantly, even after stimulation by TGF-β1 or IL-1β.…”

Section: Discussionmentioning

confidence: 99%

“…Inhibitors targeting NGF to relieve OA pain were developed, applied to clinical trials and obtained clinically significant effect. [4][5][6] Nerve growth factor (NGF) is a member of the neurotrophic factors family, which was regarded as a promoter of sensory neuron survival, axonal growth and neurotransmission initially. 7 But later, its crucial role in nociceptor development and pain generation was made out.…”

Section: Introductionmentioning

confidence: 99%

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Estrogen Regulation of the Expression of Pain Factor NGF in Rat Chondrocytes

Shang¹,

Zhang²,

Jin³

et al. 2021

JPR

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Objective: Pain is the main symptom of osteoarthritis (OA). Nerve growth factor (NGF) plays a crucial role in the generation of OA pain. And estrogen-alone used resulted in a sustained joint pain reduction in postmenopausal women. So we aim to find whether estrogen alters chondrocytes' NGF level, affecting OA pain. Methods: Primary chondrocytes and cartilage explants isolated from Sprague Dawley rat knees were cultured with physiological concentrations of estrogen (17β-Estradiol ≥ 98%, E2), Estrogen Receptor α (ERα) inhibitor and stimulants. Then, chondrocytes NGF mRNA expression and protein release were analyzed by a quantitative real-time polymerase chain reaction (qPCR) and enzyme-linked immunosorbent assay (ELISA) respectively. Additionally, cultures were pre-incubated with MEK-ERK inhibitor to identify the signaling pathway that estrogen alters NGF mRNA and protein levels. Results: We found that chondrocytes NGF expression and release were decreased by E2. E2 also reduced chondrocytes IL-1β-stimulated or TGF-β1-stimulated NGF expression. Phosphorylated extracellular signal-regulated kinasep1/2 (p-ERK1/2) signals were detected stronger than the control group by Western Blotting (WB). When we cultured chondrocytes with PD98059 (MEK-ERK inhibitor, PD), NGF mRNA expression was added to 1.41Ct (2.07±0.1 fold). Conclusion:We showed that E2 reduces chondrocytes NGF expression significantly, even after stimulation by TGF-β1 or IL-1β. MEK-ERK signaling is involved in this process.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Estrogen Regulation of the Expression of Pain Factor NGF in Rat Chondrocytes

Shang¹,

Zhang²,

Jin³

et al. 2021

JPR

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“…Recently, another phase III clinical trial evaluated 849 patients with hip and/or knee OA who had not responded to or could not tolerate standard-of-care analgesics. Patients received SC Tanezumab 2.5 mg or 5 mg or placebo every 8 weeks (Berenbaum et al, 2020). The results showed that Tanezumab 5 mg statistically significantly improved pain, physical function and PGA, and Tanezumab 2.5 mg significantly improved pain and physical function, but did not improve PGA (Berenbaum et al, 2020).…”

Section: Monoclonal Antibodies Neutralizing Nerve Growth Factormentioning

confidence: 99%

New Trends in Pharmacological Treatments for Osteoarthritis

et al. 2021

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Osteoarthritis (OA) is the leading cause of function loss and disability among the elderly, with significant burden on the individual and society. It is a severe disease for its high disability rates, morbidity, costs, and increased mortality. Multifactorial etiologies contribute to the occurrence and development of OA. The heterogeneous condition poses a challenge for the development of effective treatment for OA; however, emerging treatments are promising to bring benefits for OA management in the future. This narrative review will discuss recent developments of agents for the treatment of OA, including potential disease-modifying osteoarthritis drugs (DMOADs) and novel therapeutics for pain relief. This review will focus more on drugs that have been in clinical trials, as well as attractive drugs with potential applications in preclinical research. In the past few years, it has been realized that a complex interaction of multifactorial mechanisms is involved in the pathophysiology of OA. The authors believe there is no miracle therapeutic strategy fitting for all patients. OA phenotyping would be helpful for therapy selection. A variety of potential therapeutics targeting inflammation mechanisms, cellular senescence, cartilage metabolism, subchondral bone remodeling, and the peripheral nociceptive pathways are expected to reshape the landscape of OA treatment over the next few years. Precise randomized controlled trials (RCTs) are expected to identify the safety and efficacy of novel therapies targeting specific mechanisms in OA patients with specific phenotypes.

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“…Results from the double-blind, randomized Phase 3 NCT02709486 study of the analgesic efficacy and safety of the SC administration of tanezumab 2.5 mg or 5 mg vs. placebo in patients with OA of the hip or knee were recently reported. 59 In this study, 849 patients received tanezumab or matching placebo (tanezumab 2.5 mg n = 283, tanezumab 5 mg n = 284, placebo n = 282) every 8 weeks for 24 weeks (three doses). The three primary endpoints were (1) change from baseline to Week 24 in Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Pain, (2) WOMAC Physical Function, and (3) Patient’s Global Assessment of OA (PGA-OA).…”

Section: Antibody Therapeutics Undergoing First Regulatory Review Inmentioning

confidence: 99%

Antibodies to watch in 2021

Kaplon

Reichert²

2021

mAbs

274

205

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In this 12 th annual installment of the Antibodies to Watch article series, we discuss key events in antibody therapeutics development that occurred in 2020 and forecast events that might occur in 2021. The coronavirus disease 2019 (COVID-19) pandemic posed an array of challenges and opportunities to the healthcare system in 2020, and it will continue to do so in 2021. Remarkably, by late November 2020, two anti-SARS-CoV antibody products, bamlanivimab and the casirivimab and imdevimab cocktail, were authorized for emergency use by the US Food and Drug Administration (FDA) and the repurposed antibodies levilimab and itolizumab had been registered for emergency use as treatments for COVID-19 in Russia and India, respectively. Despite the pandemic, 10 antibody therapeutics had been granted the first approval in the US or EU in 2020, as of November, and 2 more (tanezumab and margetuximab) may be granted approvals in December 2020.* In addition, prolgolimab and olokizumab had been granted first approvals in Russia and cetuximab saratolacan sodium was first approved in Japan. The number of approvals in 2021 may set a record, as marketing applications for 16 investigational antibody therapeutics are already undergoing regulatory review by either the FDA or the European Medicines Agency. Of these 16 mAbs, 11 are possible treatments for non-cancer indications and 5 are potential treatments for cancer. Based on the information publicly available as of November 2020, 44 antibody therapeutics are in late-stage clinical studies for non-cancer indications, including 6 for COVID-19, and marketing applications for at least 6 (leronlimab, tezepelumab, faricimab, ligelizumab, garetosmab, and fasinumab) are planned in 2021. In addition, 44 antibody therapeutics are in late-stage clinical studies for cancer indications. Of these 44, marketing application submissions for 13 may be submitted by the end of 2021. *Note added in proof on key events announced during December 1-21, 2020: margetuximab-cmkb and ansuvimab-zykl were approved by FDA on December 16 and 21, 2020, respectively; biologics license applications were submitted for ublituximab and amivantamab.

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Subcutaneous tanezumab for osteoarthritis of the hip or knee: efficacy and safety results from a 24-week randomised phase III study with a 24-week follow-up period

Cited by 116 publications

References 31 publications

Estrogen Regulation of the Expression of Pain Factor NGF in Rat Chondrocytes

Estrogen Regulation of the Expression of Pain Factor NGF in Rat Chondrocytes

New Trends in Pharmacological Treatments for Osteoarthritis

Antibodies to watch in 2021

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