Targeting Nerve Growth Factor for Pain Management in Osteoarthritis—Clinical Efficacy and Safety

Dietz, Brett W.; Nakamura, Mary C.; Bell, Matthew; Lane, Nancy E.

doi:10.1016/j.rdc.2020.12.003

Cited by 13 publications

(10 citation statements)

References 58 publications

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“…42 These drugs may reduce the concentration of free NGF, prevent NGF from binding to TrkA, or prevent TrkA from being activated and thus play a role in pain treatment. 12,24 Our meta-analysis showed that the incidence of AEs in the treatment group was higher than that in the control group, but the incidence of SAEs was similar between the 2 groups.…”

Section: Discussionmentioning

confidence: 77%

“…The most common AEs associated with the use of anti-NGF antibodies include peripheral edema, joint and limb pain, and peripheral neuropathy. 12,33,35,41 Less than 10% of patients have neuropathy. 12 Symptoms of abnormal peripheral sensation are usually mild to moderate, transient in nature, and without continuous changes on neurological examination, and most AEs disappeared before the end of the study by Dietz et al 12 Early clinical trial studies have shown that rapidly progressive OA is a potential SAE.…”

Section: Discussionmentioning

confidence: 99%

“…12,33,35,41 Less than 10% of patients have neuropathy. 12 Symptoms of abnormal peripheral sensation are usually mild to moderate, transient in nature, and without continuous changes on neurological examination, and most AEs disappeared before the end of the study by Dietz et al 12 Early clinical trial studies have shown that rapidly progressive OA is a potential SAE. 3,17,35 The United States Food and Drug Administration concluded that tanezumab was unrelated to an increased risk of osteonecrosis.…”

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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Efficacy and Safety of Anti–Nerve Growth Factor Antibody Therapy for Hip and Knee Osteoarthritis: A Meta-analysis

Gao

Huang

et al. 2022

Orthopaedic Journal of Sports Medicine

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Background: The efficacy and safety of anti–nerve growth factor (NGF) antibody therapy used for osteoarthritis (OA) pain are controversial. Purpose: To evaluate the efficacy and safety of anti-NGF antibody therapy via a meta-analysis of randomized controlled trials (RCTs). Study Design: Systematic review; Level of evidence, 1. Methods: PubMed, the Cochrane Central Register of Controlled Trials, Embase, and the Web of Science databases were searched for RCTs assessing anti-NGF antibody treatments for hip and knee OA. A total of 623 records were retrieved from the databases. A random-effects model was used to assess primary and secondary outcomes. Bias was assessed using the Cochrane Collaboration tool, funnel plots, and the Egger test. Subgroup analyses were used to assess the efficacy and safety of the independent variables. Sensitivity analysis was conducted to evaluate the effectiveness of tanezumab and the effectiveness of anti-NGF antibodies compared to active comparator drugs. We present the effects of dose, administration mode, and treatment duration on the efficacy and safety of anti-NGF antibody therapy. Results: There were 19 RCTs included in our meta-analysis. Anti-NGF antibody treatment showed significant improvements on the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) for pain, physical function, and stiffness as well as on a patient global assessment (PGA). The overall standardized mean differences were as follows: WOMAC pain (–0.31 [95% CI, –0.36 to –0.26]; Z = 11.75; P < .001; I 2 = 38%), WOMAC physical function (−0.36 [95% CI, –0.41 to –0.30]; Z = 12.67; P < .001; I 2 = 44%), WOMAC stiffness (–3.59 [95% CI, –4.87 to –2.30]; Z = 5.47; P < .001; I 2 = 98%), and PGA (−0.28 [95% CI, –0.34 to –0.22]; Z = 9.39; P < .001; I 2 = 50%). Anti-NGF antibody treatment resulted in a greater incidence of adverse events (risk ratio, 1.09 [95% CI, 1.06 to 1.12]; Z = 5.60; P < .001; I 2 = 0%). The incidence of serious adverse events was similar between the treatment and control groups (risk ratio, 1.15 [95% CI, 0.98 to 1.34]; Z = 1.71; P = .09; I 2 = 0%). Conclusion: Anti-NGF antibody treatment significantly relieved pain and improved function in patients with hip and knee OA. However, no conclusion could be drawn regarding the optimal treatment plan for anti-NGF antibodies when all 3 variables (dose, administration mode, and treatment duration) were combined in the analyses.

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Section: Discussionmentioning

confidence: 77%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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Efficacy and Safety of Anti–Nerve Growth Factor Antibody Therapy for Hip and Knee Osteoarthritis: A Meta-analysis

Gao

Huang

et al. 2022

Orthopaedic Journal of Sports Medicine

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“…Nerve growth factor (NGF) has been suggested as a therapeutic target for osteoarthritis pain, and clinical trials with antibodies that neutralize NGF reported positive results in terms of pain relief (11,12). Using rodent models of osteoarthritis, we and others have shown that a unique subset of nociceptors ('silent nociceptors') become responsive to mechanical stimuli (indicating peripheral sensitization) during the course of disease (13)(14)(15)(16).…”

Section: Main Text: Introductionmentioning

confidence: 99%

Piezo2 expressing nociceptors mediate mechanical sensitization in experimental osteoarthritis

Obeidat

Wood

Ishihara

et al. 2022

Preprint

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Osteoarthritis is a very common painful joint disease, for which few treatment options exist. New non-opioid targets are needed for addressing osteoarthritis pain, which is mechanical in nature and associated with daily activities such as walking and climbing stairs. Piezo2 has been implicated in development of mechanical pain, but the mechanisms by which this occurs remain poorly understood. We observed that in two different murine models of osteoarthritis (destabilization of the medial meniscus and natural aging), nociceptor-specific Piezo2 conditional knock-out mice developed osteoarthritic joint damage, but were protected from associated mechanical sensitization. Since nerve growth factor (NGF) is known to mediate nociceptor sensitization, and antibodies that neutralize NGF are effective as a treatment for osteoarthritis pain, we explored the effects of intra-articularly injected NGF on the development of mechanical joint pain. Wild-type mice developed knee swelling and mechanical pain in response to intra-articular NGF, while nociceptor-specific Piezo2 conditional knock-out mice were protected from these effects. Single cell RNA sequencing and in situ hybridization of mouse and human lumbar dorsal root ganglia (DRG) revealed that a subset of nociceptors co-express Piezo2 and Ntrk1 (the gene that encodes the NGF receptor TrkA). These results indicate that Piezo2 plays a key role in nociceptor sensitization processes in the osteoarthritic joint, and targeting Piezo2 may represent a novel therapy for osteoarthritis pain control.

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Neurotrophic Factors in the Pathogenesis and Treatment of Diabetic Neuropathy

Calcutt

2023

Contemporary Diabetes

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Targeting Nerve Growth Factor for Pain Management in Osteoarthritis—Clinical Efficacy and Safety

Cited by 13 publications

References 58 publications

Efficacy and Safety of Anti–Nerve Growth Factor Antibody Therapy for Hip and Knee Osteoarthritis: A Meta-analysis

Efficacy and Safety of Anti–Nerve Growth Factor Antibody Therapy for Hip and Knee Osteoarthritis: A Meta-analysis

Piezo2 expressing nociceptors mediate mechanical sensitization in experimental osteoarthritis

Neurotrophic Factors in the Pathogenesis and Treatment of Diabetic Neuropathy

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