Control of Arthritis Pain with Anti–Nerve-Growth Factor: Risk and Benefit
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Arthritis is characterized by pain and inflammation. Recently, attention has been focused on nerve-growth factor (NGF), a neurotrophin that is a key regulator of peripheral nociception because it mediates overexpression of proinflammatory neuron-derived molecules such as substance P, serotonin, and calcitonin gene-related peptide. Antibodies have been generated for NGF and its receptor that are effective in reducing pain in preclinical pain models, and clinical trials in patients with advanced knee and hip osteoarthritis and low-back pain. Results show pain reduction is rapid and sustained. Adverse events with anti-NGF included transient paraesthesia and edema, rapidly progressive OA, and, in a small number of patients treated with both anti-NGF and nonsteroidal anti-inflammatory drugs, osteonecrosis. Inhibition of the NGF-stimulated nociceptive pathway seems to be effective; however, the adverse effects require further investigation.
KeywordsNeurogenic inflammation Nerve-growth factor NGF Receptor antagonists Rheumatic diseases Arthritis Pain Risk Benefit Antagonists
Dr Seidel has served on a board for Pfizer. Dr Lane has served as a consultant for, and had travel expenses covered/reimbursed by, Pfizer.
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- 8.Reinhardt RR, Laub JB, Fricke JR, et al. Comparison of neurokinin-1 antagonist, L-745,030, to placebo, acetominophen and ibuprofen in the dental pain model. Clin Pharmacol Ther. 1998;63(2):168.Google Scholar
- 35.Nagashima H, Suzuki M, Araki S, Tanezumab Investigators. Preliminary assessment of the safety and efficacy of tanezumab in Japanese patients with moderate to severe osteoarthritis of the knee: a randomized, double-blind, dose-escalation, placebo-controlled study. Osteoarthr Cart. 2011;19(12):1405–12.CrossRefGoogle Scholar
- 36.Tiseo P, Kivitz AJ, Ervin JE, et al. REGN475/SAR164877, a nerve growth factor inhibitor, in osteoarthritis patients with moderate to severe knee pain: results of a phase 2, randomized, double-blind, placebo-controlled study. Arthr Rheum. 2010;62 Suppl 10:710.Google Scholar
- 37.Feist E, Balanescu A, Wolfram G, et al. Efficacy and safety of tanezumab added on to diclofenac in patients with knee or hip osteoarthritis (NCT00864097). Arthr Rheum. 2011;63 Suppl 10:1096.Google Scholar
- 38.Yazici Y, Ekman EF, Greenberg HS, et al. Efficacy of tanezumab compared with non-steroidal anti-inflammatory drugs in patients with knee or hip osteoarthritis (NCT00809354). Arthr Rheum. 2011;63 Suppl 10:828.Google Scholar
- 45.Ghilardi JR, Freeman KT, Jimenez-Andrade JM et al. Neuroplasticity of sensory and sympathetic nerve fibers in the painful arthritic joint. Arthr Rheum 2012; in press.Google Scholar