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Targeted Therapy for Primary Sjögren’s Syndrome: Where are We Now?
BioDrugs ( IF 5.4 ) Pub Date : 2021-11-03 , DOI: 10.1007/s40259-021-00505-7
Bin Wang 1 , Shiju Chen 1 , Yan Li 1 , Jingxiu Xuan 1 , Yuan Liu 1 , Guixiu Shi 1, 2
Affiliation  

Primary Sjögren's syndrome (pSS) is an autoimmune exocrinopathy characterized by dryness symptoms. This review briefly describes recent advances in the targeted therapies for pSS. Biologics evaluated for pSS treatment mainly include B cell-depleting agents, inhibitors of B cell activation, and agents that target co-signaling molecules or proinflammatory cytokines. Small molecule inhibitors that target signaling pathways have also been evaluated. However, current evidence for the efficacy of targeted therapies in pSS is still sparse. Although ianalumab (an anti–B cell-activating factor [BAFF]-receptor antibody) and iscalimab (an anti-CD40 antibody) are promising biologics for pSS, their efficacy still needs to be evaluated in larger clinical trials. For other biologics, clinical trials have found no differences versus placebo in the change from baseline in European League Against Rheumatism Sjögren's Syndrome Disease Activity Index (ESSDAI) score and fatigue score. Possible causes of the disappointing outcomes mainly include the inefficacy of those evaluated biologics in treating pSS, the high heterogeneous nature of pSS, irreversible exocrine glandular failure at advanced disease stages, inappropriate recruitment strategy in clinical trials, and outcome measures. Early diagnosis and glandular function-centered outcome measures may help to improve the current situation in the systemic therapy of pSS.



中文翻译:

原发性干燥综合征的靶向治疗:我们现在在哪里?

原发性干燥综合征 (pSS) 是一种以干燥症状为特征的自身免疫性外分泌病。本综述简要介绍了 pSS 靶向治疗的最新进展。用于 pSS 治疗的生物制剂主要包括 B 细胞耗竭剂、B 细胞活化抑制剂和靶向共信号分子或促炎细胞因子的药物。还评估了靶向信号通路的小分子抑制剂。然而,目前关于靶向治疗在 pSS 中的疗效的证据仍然很少。尽管 ianalumab(一种抗 B 细胞激活因子 [BAFF] 受体抗体)和 iscalimab(一种抗 CD40 抗体)是治疗 pSS 的有前途的生物制剂,但它们的疗效仍需要在更大规模的临床试验中进行评估。对于其他生物制剂,临床试验发现与安慰剂相比,欧洲抗风湿病联盟干燥综合征疾病活动指数 (ESSDAI) 评分和疲劳评分从基线的变化没有差异。结果令人失望的可能原因主要包括那些被评估的生物制剂治疗 pSS 的无效性、pSS 的高度异质性、晚期疾病阶段不可逆的外分泌腺功能衰竭、临床试验中不适当的招募策略和结果测量。早期诊断和以腺功能为中心的结果测量可能有助于改善 pSS 全身治疗的现状。结果令人失望的可能原因主要包括那些被评估的生物制剂治疗 pSS 的无效性、pSS 的高度异质性、晚期疾病阶段不可逆的外分泌腺功能衰竭、临床试验中不适当的招募策略和结果测量。早期诊断和以腺功能为中心的结果测量可能有助于改善 pSS 全身治疗的现状。结果令人失望的可能原因主要包括那些被评估的生物制剂治疗 pSS 的无效性、pSS 的高度异质性、晚期疾病阶段不可逆的外分泌腺功能衰竭、临床试验中不适当的招募策略和结果测量。早期诊断和以腺功能为中心的结果测量可能有助于改善 pSS 全身治疗的现状。

更新日期:2021-11-03
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