Hochberg M C
Departments of Medicine and Epidemiology and Public Health, University of Maryland School of Medicine and the Medical Care Clinical Center, VA Maryland Health Care System, Baltimore, MD, USA.
Osteoarthritis Cartilage. 2015 Jan;23 Suppl 1:S18-21. doi: 10.1016/j.joca.2014.10.005.
Reports of serious joint adverse events (AEs) due to osteonecrosis were noted during randomized placebo-controlled clinical trials of monoclonal antibodies to nerve growth factor (NGF), including tanezumab and fulranumab.
All available medical records from subjects with reported cases of osteonecrosis, as well as records of subjects who underwent joint replacement during these studies, were reviewed by an independent adjudication committee that was established by each company; the committees were different for each company and included distinct individual experts. Cases were categorized as having definite osteonecrosis, normal or rapid progression of osteoarthritis (OA), another diagnosis or unable to determine the underlying diagnosis.
The vast majority of investigator reported cases of osteonecrosis were adjudicated as either normal or rapid progression of OA. Indeed, the syndrome of rapid progression of OA associated with chondrolysis and bone destruction appears to be a safety signal that is associated with not only increasing doses of anti-NGF antibodies but also concomitant therapy with nonsteroidal anti-inflammatory drugs.
These results have implications for future clinical trials of anti-NGF agents in OA and other painful conditions.
在神经生长因子（NGF）单克隆抗体（包括他尼珠单抗和氟罗那单抗）的随机安慰剂对照临床试验中，发现了因骨坏死导致严重关节不良事件（AE）的报告。
各公司设立的独立判定委员会对所有报告有骨坏死病例受试者的可用医疗记录以及这些研究期间接受关节置换的受试者记录进行了审查；各公司的委员会不同，且包括不同的专家个体。病例被分类为确诊骨坏死、骨关节炎（OA）正常或快速进展、其他诊断或无法确定潜在诊断。
绝大多数研究者报告的骨坏死病例被判定为OA正常或快速进展。实际上，与软骨溶解和骨破坏相关的OA快速进展综合征似乎是一个安全信号，不仅与抗NGF抗体剂量增加有关，还与非甾体抗炎药的联合治疗有关。
这些结果对OA和其他疼痛性疾病中抗NGF药物的未来临床试验具有启示意义。
