University of Michigan Lupus Program, Division of Rheumatology, Department of Internal Medicine, University of Michigan, Ann Arbor, Michigan, USA.
Curr Opin Rheumatol. 2024 May 1;36(3):169-175. doi: 10.1097/BOR.0000000000001003. Epub 2024 Feb 1.
The approval of belimumab and anifrolumab has expanded the scope of treatment for systemic lupus erythematosus (SLE) patients. However, many patients remain refractory to currently available therapies and suffer from drug toxicities. This review will discuss approved and target-specific therapeutics in development that bring hope for better SLE treatments.
Since the last review on this subject in the journal, the FDA has approved anifrolumab and belimumab for SLE and lupus nephritis (LN), respectively. A fully humanized anti-CD20, obinutuzumab, met the primary end point in a phase II trial in LN. A Tyk2 inhibitor, deucravacitinib, and an antibody targeting plasmacytoid dendritic cells, litifilimab, met the primary end point in phase II trials in SLE and cutaneous lupus erythematosus (CLE). Ustekinumab and baricitinib met the primary end point in phase II but not in phase III trials.
While many drug candidates which met the end points in phase II trials have failed phase III trials, the number of target-specific therapies for SLE has continued to expand.
贝鲁单抗和阿尼鲁单抗的批准扩大了系统性红斑狼疮 (SLE) 患者的治疗范围。然而,许多患者仍然对现有治疗方法产生抗药性,并遭受药物毒性的影响。本综述将讨论正在开发中的已批准和针对特定靶点的治疗方法,这些方法为更好的 SLE 治疗带来了希望。
自该主题上次在该期刊上发表综述以来,FDA 已分别批准阿尼鲁单抗和贝鲁单抗用于治疗 SLE 和狼疮肾炎 (LN)。一种完全人源化抗 CD20 抗体奥滨尤妥珠单抗在 LN 的 II 期试验中达到了主要终点。一种 Tyk2 抑制剂德瓦鲁单抗和一种针对浆细胞样树突状细胞的抗体利替利单抗在 SLE 和皮肤红斑狼疮 (CLE) 的 II 期试验中达到了主要终点。乌司奴单抗和巴利昔单抗在 II 期试验中达到了主要终点,但在 III 期试验中没有达到。
虽然许多在 II 期试验中达到终点的药物候选物在 III 期试验中失败,但针对 SLE 的靶向治疗方法的数量继续扩大。