银屑病
医学
银屑病面积及严重程度指数
药代动力学
加药
药效学
内科学
胃肠病学
白细胞介素17
安慰剂
药理学
皮肤活检
趋化因子
20立方厘米
活检
皮肤病科
炎症
病理
趋化因子受体
替代医学
作者
Ruth Oliver,James G. Krueger,Sophie Glatt,Pavan Vajjah,Catrina Mistry,Matthew J. Page,Hannah Edwards,Sandra Garcet,X Li,Benjamin Dizier,Asher Maroof,Mark Watling,A El Baghdady,Dominique Baeten,Lucian Ionescu,Stevan Shaw
摘要
Bimekizumab is a monoclonal antibody that selectively inhibits both interleukin (IL)-17A and IL-17F, which is currently under investigation for treatment of moderate-to-severe plaque psoriasis. Maintenance dosing every 4 weeks is well established with IL-17 inhibitors for psoriasis.To investigate the possible dosing interval during bimekizumab maintenance therapy to maintain clear skin, to inform phase III studies.Forty-nine patients with moderate-to-severe plaque psoriasis received bimekizumab 320 mg at weeks 0/4, followed at week 16 by bimekizumab 320 mg (n = 17) or placebo (n = 32). Efficacy, safety, pharmacokinetics, immunogenicity and biopsy transcriptomic analyses were assessed to week 28.At week 8, 47% of patients achieved a 100% improvement from baseline in Psoriasis Area and Severity Index (PASI 100), increasing to 57% at week 12 (8 weeks after the second dose) before decreasing. In those who received bimekizumab at week 16, PASI 100 rate increased to comparable peak levels at week 20, but reduced by week 28 to 41% (12 weeks after the third dose). The week 8 transcriptional signature observed in lesional psoriatic skin rapidly normalized to levels consistent with nonlesional skin, resulting in molecular remission. Keratinocyte-related gene products such as CXCL1 (C-X-C motif chemokine ligand 1), IL-8 (encoded by the CXCL8 gene), CCL20 (C-C motif chemokine 20), IL-36γ and IL-17C were profoundly normalized to levels associated with nonlesional skin.Here, inhibition of IL-17F in addition to IL-17A resulted in rapid, deep clinical responses. Additionally, profound normalization of keratinocyte biology and the psoriatic transcriptome was observed, including normalization of both IL17 and IL23 gene expression by week 8. These data provide evidence to support evaluation of bimekizumab maintenance dosing both every 8 and every 4 weeks in phase III clinical trials.
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