Cleveland Clinic Lou Ruvo Center for Brain Health, Las Vegas, NV, USA.
Lundbeck, Deerfield, IL, USA.
J Alzheimers Dis. 2019;67(3):779-794. doi: 10.3233/JAD-180766.
Although Alzheimer's disease (AD) is the world's leading cause of dementia and the population of patients with AD continues to grow, no new therapies have been approved in more than a decade. Many clinical trials of single-agent therapies have failed to affect disease progression or symptoms compared with placebo. The complex pathophysiology of AD may necessitate combination treatments rather than monotherapy. The goal of this narrative literature review is to describe types of combination therapy, review the current clinical evidence for combination therapy regimens (both symptomatic and disease-modifying) in the treatment of AD, describe innovative clinical trial study designs that may be effective in testing combination therapy, and discuss the regulatory and drug development landscape for combination therapy. Successful combination therapies in other complex disorders, such as human immunodeficiency virus, may provide useful examples of a potential path forward for AD treatment.
尽管阿尔茨海默病(AD)是全球导致痴呆的主要原因,且 AD 患者人数持续增长,但在过去十年中,尚无新疗法获得批准。与安慰剂相比,许多针对单一药物疗法的临床试验未能影响疾病进展或症状。AD 的复杂病理生理学可能需要联合治疗而不是单一药物治疗。本叙述性文献综述的目的是描述联合治疗的类型,综述 AD 治疗中联合治疗方案(包括症状性和疾病修饰性)的当前临床证据,描述可能对测试联合治疗有效的创新临床试验研究设计,并讨论联合治疗的监管和药物开发前景。在人类免疫缺陷病毒等其他复杂疾病中成功的联合疗法可能为 AD 治疗提供一个潜在的前进方向。