Department of Chemical, Biochemical & Environmental Engineering, University of Maryland, Baltimore County, Baltimore, MD, USA.
Department of Medicine, Division of Rheumatology & Clinical Immunology, University of Maryland School of Medicine, Baltimore, MD, USA.
Trends Mol Med. 2021 Feb;27(2):152-171. doi: 10.1016/j.molmed.2020.09.009. Epub 2020 Oct 9.
Systemic lupus erythematosus (SLE) is a multisystem, chronic autoimmune disease where treatment varies by patient and disease activity. Strong preclinical results and clinical correlates have motivated development of many drugs, but many of these have failed to achieve efficacy in clinical trials. FDA approval of belimumab in 2011 was the first successful SLE drug in nearly six decades. In this article, we review insights into the molecular and clinical heterogeneity of SLE from transcriptomics studies and detail their potential impact on drug development and clinical practices. We critically examine the pipeline of SLE drugs, including past failures and their associated lessons and current promising approaches. Finally, we identify opportunities for integrating these findings and drug development with new multidisciplinary advances to enhance future SLE treatment.
系统性红斑狼疮 (SLE) 是一种多系统、慢性自身免疫性疾病，其治疗因患者和疾病活动而异。强有力的临床前结果和临床相关性促使许多药物得到了发展，但其中许多药物在临床试验中都未能显示出疗效。2011 年 FDA 批准贝利尤单抗是近六十年来首个成功治疗 SLE 的药物。本文我们通过转录组学研究综述了 SLE 分子和临床异质性的相关见解，并详细阐述了它们对药物开发和临床实践的潜在影响。我们批判性地审视了 SLE 药物的研发管道，包括过去的失败及其相关经验教训，以及当前有前景的方法。最后，我们确定了将这些发现和药物开发与新的多学科进展相结合的机会，以增强未来 SLE 的治疗效果。
