Complement plays a key role in immunosurveillance and homeostasis. When dysregulated or overactivated, complement can become a pathological effector, as seen in several inflammatory disorders, including periodontal disease. Recently, clinical correlative studies and preclinical mechanistic investigations have collectively demonstrated that complement is hyperactivated during periodontitis and that targeting its central component (C3) provides therapeutic benefit in nonhuman primates (NHPs). The preclinical efficacy of a C3-targeted drug candidate combined with excellent safety and pharmacokinetic profiles supported its use in a recent Phase IIa clinical study in which C3 inhibition resolved gingival inflammation in patients with periodontal disease. We posit that C3-targeted intervention might represent a novel and transformative host-modulation therapy meriting further investigation in Phase III clinical trials for the treatment of periodontitis.

补体在免疫监视和体内平衡中发挥着关键作用。当补体失调或过度激活时，补体可能成为病理效应器，如在包括牙周病在内的多种炎症性疾病中所见。最近，临床相关研究和临床前机制研究共同证明，补体在牙周炎期间过度激活，并且针对其中心成分 (C3) 为非人灵长类动物 (NHP) 提供了治疗益处。 C3 靶向候选药物的临床前疗效以及出色的安全性和药代动力学特征支持其在最近的 IIa 期临床研究中的使用，其中 C3 抑制解决了牙周病患者的牙龈炎症。我们认为，C3 靶向干预可能代表一种新颖的、变革性的宿主调节疗法，值得在治疗牙周炎的 III 期临床试验中进一步研究。