PDF(Pubmed)
Abstract：
UNASSIGNED: There is no US Food and Drug Administration-approved treatment for pityriasis rubra pilaris (PRP), and it is common for patients to fail to experience improvement with several systemic options. Involvement of interleukin (IL) 23 suggests a potential therapeutic target.
UNASSIGNED: To determine whether guselkumab, an IL-23p19 inhibitor, provides clinical improvement for participants with PRP and better understand gene and protein dysregulation in PRP.
UNASSIGNED: This single-arm, investigator-initiated nonrandomized trial was conducted from October 2019 to August 2022 at a single-center academic university with participants from 8 states in the US. In total, 14 adults with moderate to severe PRP were enrolled; 12 completed the trial. Age-matched and sex-matched healthy controls provided skin and blood for proteomic and transcriptomic studies. The primary outcome was observed at 24 weeks, and additional follow-up occurred at 36 weeks.
UNASSIGNED: Guselkumab is a fully human immunoglobulin G1 λ monoclonal antibody that selectively binds and inhibits the p19 subunit of IL-23. Subcutaneous injections were given at the US Food and Drug Administration-approved dosing schedule for psoriasis over a 24-week period.
UNASSIGNED: The primary outcome was the mean change in the Psoriasis Area Severity Index (PASI) score at week 24. Secondary outcomes included pruritus, Dermatology Life Quality Index score, clinical response at week 36, and association with transcriptomics and proteomics expression.
UNASSIGNED: A per-protocol analysis was performed for the cohort of 4 female and 8 male patients who had a mean (SD) age of 56.5 (18.7) years. The mean improvement in PASI score, pruritus, and Dermatology Life Quality Index score was 61.8% (P < .001), 62.3% (P = .001), and 60.2% (P < .001), respectively. Nine participants (75%) achieved a 50% improvement in PASI. Among these clinical responders, at week 36, 8 of 9 achieved PASI75, and 6 of 9 achieved PASI90. No participants had pathogenic CARD14 gene variations. There was 1 serious adverse event that was not associated with the study drug. Proteomics and gene expression profiles identified dysregulation of a predominance of inflammatory pathways (such as T helper 17 and nuclear factor κ B) in participants with PRP who later responded well to treatment with guselkumab and stronger dysregulation of keratinocyte development pathways in individuals who did not respond to guselkumab.
UNASSIGNED: The results of this nonrandomized trial suggest that guselkumab has efficacy in treating refractory moderate to severe adult PRP.
UNASSIGNED: ClinicalTrials.gov Identifier: NCT03975153.
UNASSIGNED: To determine whether guselkumab, an IL-23p19 inhibitor, provides clinical improvement for participants with PRP and better understand gene and protein dysregulation in PRP.
UNASSIGNED: This single-arm, investigator-initiated nonrandomized trial was conducted from October 2019 to August 2022 at a single-center academic university with participants from 8 states in the US. In total, 14 adults with moderate to severe PRP were enrolled; 12 completed the trial. Age-matched and sex-matched healthy controls provided skin and blood for proteomic and transcriptomic studies. The primary outcome was observed at 24 weeks, and additional follow-up occurred at 36 weeks.
UNASSIGNED: Guselkumab is a fully human immunoglobulin G1 λ monoclonal antibody that selectively binds and inhibits the p19 subunit of IL-23. Subcutaneous injections were given at the US Food and Drug Administration-approved dosing schedule for psoriasis over a 24-week period.
UNASSIGNED: The primary outcome was the mean change in the Psoriasis Area Severity Index (PASI) score at week 24. Secondary outcomes included pruritus, Dermatology Life Quality Index score, clinical response at week 36, and association with transcriptomics and proteomics expression.
UNASSIGNED: A per-protocol analysis was performed for the cohort of 4 female and 8 male patients who had a mean (SD) age of 56.5 (18.7) years. The mean improvement in PASI score, pruritus, and Dermatology Life Quality Index score was 61.8% (P < .001), 62.3% (P = .001), and 60.2% (P < .001), respectively. Nine participants (75%) achieved a 50% improvement in PASI. Among these clinical responders, at week 36, 8 of 9 achieved PASI75, and 6 of 9 achieved PASI90. No participants had pathogenic CARD14 gene variations. There was 1 serious adverse event that was not associated with the study drug. Proteomics and gene expression profiles identified dysregulation of a predominance of inflammatory pathways (such as T helper 17 and nuclear factor κ B) in participants with PRP who later responded well to treatment with guselkumab and stronger dysregulation of keratinocyte development pathways in individuals who did not respond to guselkumab.
UNASSIGNED: The results of this nonrandomized trial suggest that guselkumab has efficacy in treating refractory moderate to severe adult PRP.
UNASSIGNED: ClinicalTrials.gov Identifier: NCT03975153.
摘要：
■没有美国食品和药物管理局批准的治疗毛发红疹糠疹（PRP），患者通常无法通过几种系统选择获得改善。白细胞介素（IL）23的参与表明了一个潜在的治疗目标。
■为了确定guselkumab是否，IL-23p19抑制剂，为PRP患者提供临床改善，并更好地了解PRP中的基因和蛋白质失调。
■这种单臂，研究者发起的非随机试验于2019年10月至2022年8月在一所单中心学术大学进行,参与者来自美国8个州.总的来说,14名患有中度至重度PRP的成年人被纳入；12名完成了试验。年龄匹配和性别匹配的健康对照为蛋白质组学和转录组学研究提供皮肤和血液。主要结果在24周观察，并在36周时进行了额外的随访。
■Guselkumab是一种全人免疫球蛋白G1λ单克隆抗体，可选择性结合并抑制IL-23的p19亚基。在24周的时间内，根据美国食品和药物管理局批准的牛皮癣给药方案进行皮下注射。
■主要结果是第24周时银屑病面积严重程度指数（PASI）评分的平均变化。次要结果包括瘙痒，皮肤病生活质量指数评分,36周时的临床反应，以及与转录组学和蛋白质组学表达的关联。
■对平均(SD)年龄为56.5(18.7)岁的4名女性和8名男性患者的队列进行了符合方案分析。PASI得分的平均改善，瘙痒,皮肤病生活质量指数得分为61.8%(P<.001)，62.3%(P=.001)，和60.2%（P<.001），分别。9名参与者（75％）的PASI改善了50％。在这些临床反应者中，在第36周，9人中有8人达到PASI75，9人中有6人达到PASI90。没有参与者有致病性CARD14基因变异。有1例严重不良事件与研究药物无关。蛋白质组学和基因表达谱确定了PRP参与者的炎症途径（例如T辅助细胞17和核因子κB）的主要失调，这些参与者后来对guselkumab的治疗反应良好，对guselkumab无反应的个体角质形成细胞发育途径的失调更强。
■这项非随机试验的结果表明，guselkumab对治疗难治性中度至重度成人PRP有疗效。
■ClinicalTrials.gov标识符：NCT03975153。
■为了确定guselkumab是否，IL-23p19抑制剂，为PRP患者提供临床改善，并更好地了解PRP中的基因和蛋白质失调。
■这种单臂，研究者发起的非随机试验于2019年10月至2022年8月在一所单中心学术大学进行,参与者来自美国8个州.总的来说,14名患有中度至重度PRP的成年人被纳入；12名完成了试验。年龄匹配和性别匹配的健康对照为蛋白质组学和转录组学研究提供皮肤和血液。主要结果在24周观察，并在36周时进行了额外的随访。
■Guselkumab是一种全人免疫球蛋白G1λ单克隆抗体，可选择性结合并抑制IL-23的p19亚基。在24周的时间内，根据美国食品和药物管理局批准的牛皮癣给药方案进行皮下注射。
■主要结果是第24周时银屑病面积严重程度指数（PASI）评分的平均变化。次要结果包括瘙痒，皮肤病生活质量指数评分,36周时的临床反应，以及与转录组学和蛋白质组学表达的关联。
■对平均(SD)年龄为56.5(18.7)岁的4名女性和8名男性患者的队列进行了符合方案分析。PASI得分的平均改善，瘙痒,皮肤病生活质量指数得分为61.8%(P<.001)，62.3%(P=.001)，和60.2%（P<.001），分别。9名参与者（75％）的PASI改善了50％。在这些临床反应者中，在第36周，9人中有8人达到PASI75，9人中有6人达到PASI90。没有参与者有致病性CARD14基因变异。有1例严重不良事件与研究药物无关。蛋白质组学和基因表达谱确定了PRP参与者的炎症途径（例如T辅助细胞17和核因子κB）的主要失调，这些参与者后来对guselkumab的治疗反应良好，对guselkumab无反应的个体角质形成细胞发育途径的失调更强。
■这项非随机试验的结果表明，guselkumab对治疗难治性中度至重度成人PRP有疗效。
■ClinicalTrials.gov标识符：NCT03975153。
