Roemer Frank W, Hochberg Marc C, Carrino John A, Kompel Andrew J, Diaz Luis, Hayashi Daichi, Crema Michel D, Guermazi Ali
Department of Radiology, Universitätsklinikum Erlangen & Friedrich-Alexander-Universität (FAU) Erlangen-Nürnberg, Maximiliansplatz 3, 91054 Erlangen, Germany.
Chobanian & Avedisian School of Medicine, Boston University, Boston, MA, USA.
Ther Adv Musculoskelet Dis. 2023 May 29;15:1759720X231171768. doi: 10.1177/1759720X231171768. eCollection 2023.
Nerve growth factor (a-NGF) inhibitors have been developed for pain treatment including symptomatic osteoarthritis (OA) and have proven analgesic efficacy and improvement in functional outcomes in patients with OA. However, despite initial promising data, a-NGF clinical trials focusing on OA treatment had been suspended in 2010. Reasons were based on concerns regarding accelerated OA progression but were resumed in 2015 including detailed safety mitigation based on imaging. In 2021, an FDA advisory committee voted against approving tanezumab (one of the a-NGF compounds being evaluated) and declared that the risk evaluation and mitigation strategy was not sufficient to mitigate potential safety risks. Future clinical trials evaluating the efficacy of a-NGF or comparable molecules will need to define strict eligibility criteria and will have to include strategies to monitor safety closely. While disease-modifying effects are not the focus of a-NGF treatments, imaging plays an important role to evaluate eligibility of potential participants and to monitor safety during the course of these studies. Aim is to identify subjects with on-going safety findings at the time of inclusion, define those potential participants that are at increased risk for accelerated OA progression and to withdraw subjects from on-going studies in a timely fashion that exhibit imaging-confirmed structural safety events such as rapid progressive OA. OA efficacy- and a-NGF studies apply imaging for different purposes. In OA efficacy trials image acquisition and evaluation aims at maximizing sensitivity in order to capture structural effects between treated and non-treated participants in longitudinal fashion. In contrast, the aim of imaging in a-NGF trials is to enable detection of structural tissue alterations that either increase the risk of a negative outcome (eligibility) or may result in termination of treatment (safety).
神经生长因子（α-NGF）抑制剂已被开发用于疼痛治疗，包括症状性骨关节炎（OA），并且已证明对OA患者具有镇痛效果并能改善功能结局。然而，尽管最初的数据很有前景，但专注于OA治疗的α-NGF临床试验在2010年被暂停。原因是担心OA进展加速，但在2015年恢复，包括基于成像的详细安全性缓解措施。2021年，美国食品药品监督管理局（FDA）的一个咨询委员会投票反对批准他尼珠单抗（正在评估的α-NGF化合物之一），并宣称风险评估和缓解策略不足以减轻潜在的安全风险。未来评估α-NGF或类似分子疗效的临床试验将需要定义严格的入选标准，并且必须包括密切监测安全性的策略。虽然疾病修饰作用不是α-NGF治疗的重点，但成像在评估潜在参与者的入选资格以及在这些研究过程中监测安全性方面起着重要作用。目的是在纳入时识别有持续安全发现的受试者，确定那些有加速OA进展风险增加的潜在参与者，并及时从正在进行的研究中撤出那些表现出成像证实的结构安全事件（如快速进展性OA）的受试者。OA疗效和α-NGF研究将成像用于不同目的。在OA疗效试验中，图像采集和评估旨在最大化敏感性，以便以纵向方式捕捉治疗组和未治疗组参与者之间的结构效应。相比之下，α-NGF试验中成像的目的是能够检测出结构组织改变，这些改变要么增加负面结果（入选资格）的风险，要么可能导致治疗终止（安全性）。
