Department of Rheumatology and Clinical Immunology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing, China.
National Clinical Research Center for Dermatologic and Immunologic Diseases (NCRC-DID), Ministry of Science & Technology, Beijing, China.
Expert Opin Investig Drugs. 2024 Feb;33(2):105-114. doi: 10.1080/13543784.2024.2312216. Epub 2024 Jan 31.
Sjögren's syndrome is a heterogeneous autoimmune condition that impairs quality of life because of dryness, fatigue, pain, and systemic involvements. Current treatment largely depends on empirical evidence, with no effective therapy approved. Clinical trials on targeted drugs often fail to report efficacy due to common factors.
This review summarizes the pathogenesis and what caused the failure of new investigational drugs in clinical trials, highlighting solutions for more effective investigations, with greater consistency between research outcomes, clinical use, and patient needs.
Unlinked pathobiology with symptoms resulted in misidentified targets and disappointing trials. Useful stratification tools are necessary for the heterogeneous SS patients. Composite endpoints or improvements in ESSDAI scores are needed, considering the high placebo response, and the unbalance between symptom burden and disease activity. Compared to classic biologics, targeted cell therapy will be a more promising field of investigation in the coming years.
干燥综合征是一种异质性自身免疫性疾病，由于干燥、疲劳、疼痛和全身受累，影响生活质量。目前的治疗主要依赖于经验证据，没有批准有效的治疗方法。针对靶向药物的临床试验由于常见因素往往无法报告疗效。
本综述总结了发病机制以及新的临床试验中研究药物失败的原因，强调了更有效的研究解决方案，使研究结果、临床应用和患者需求之间更加一致。
症状与无关联的病理生物学导致目标错位和试验结果令人失望。对于异质性 SS 患者，有必要使用有用的分层工具。考虑到高安慰剂反应和症状负担与疾病活动之间的不平衡，需要采用复合终点或 ESSDAI 评分的改善。与经典生物制剂相比，靶向细胞治疗将是未来几年更有前途的研究领域。
