Nerve growth factor blockade for the management of osteoarthritis pain: what can we learn from clinical trials and preclinical models?
Anti-nerve growth factor (NGF) antibodies hold tremendous potential for the management of osteoarthritis pain, but clinical trials have revealed serious adverse effects that are incompletely understood. This review discusses clinical trial results along with preclinical studies that have assessed NGF blockade in experimental osteoarthritis, in order to provide insight for future studies.



Systematic reviews have revealed that anti-NGF therapy, including tanezumab, is efficacious in improving pain and function, but serious adverse events, including rapidly progressive osteoarthritis and osteonecrosis, resulted in a moratorium on trials that was only recently lifted. Within the past year, preclinical testing has revealed effects of NGF blockade on both pain behaviors and joint structure in experimental models of osteoarthritis. Similar to clinical trial results, these studies in laboratory animals demonstrated analgesic efficacy of NGF blockade. Interestingly, several animal studies have suggested detrimental effects on joint integrity as a result of treatment, particularly when treatment is started early in the disease, when joint damage is mild to moderate.



NGF blockade continues to represent a promising new approach for the treatment of osteoarthritis pain, but the actual benefits and risks remain to be fully elucidated. Preclinical models may suggest patient populations that could be best served while limiting side-effects, but future work should further investigate the mechanisms of benefits and unwanted side-effects.
Division of Rheumatology, Department of Internal Medicine, Rush University Medical Center, Chicago, Illinois, USA.
Rachel E
RE
Miller
Joel A
JA
Block
Anne-Marie
AM
Malfait
D018712:Analgesics, Non-Narcotic / Q000009:adverse effects / Q000627:therapeutic use*; D000818:Animals; D061067:Antibodies, Monoclonal, Humanized / Q000009:adverse effects / Q000627:therapeutic use; D001169:Arthritis, Experimental / Q000150:complications / Q000188:drug therapy*; D002986:Clinical Trials as Topic / Q000379:methods; D004353:Drug Evaluation, Preclinical / Q000379:methods; D006801:Humans; D020932:Nerve Growth Factor / Q000037:antagonists & inhibitors*; D010003:Osteoarthritis / Q000150:complications / Q000188:drug therapy*; D010020:Osteonecrosis / Q000139:chemically induced; D010146:Pain / Q000188:drug therapy* / Q000209:etiology; D059408:Pain Management / Q000379:methods
D018712:Analgesics, Non-Narcotic; D061067:Antibodies, Monoclonal, Humanized; D020932:Nerve Growth Factor; C549319:tanezumab
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