JEADV:Risankizumab长期治疗银屑病面积和严重程度指数以及相关的生活质量改善研究

2022-03-04 医路坦克 MedSci原创

银屑病是一种慢性、免疫介导的全身性炎症性疾病,本文研究了risankizumab治疗的中度至重度斑块状银屑病患者与ustekinumab相比,绝对PASI阈值的实现和健康相关生活质量指标的差异。

银屑病是一种慢性、免疫介导的全身性炎症性疾病,全世界约有1亿人患有银屑病。银屑病对患者的生活质量有深远的负面影响,增加早期死亡和合并疾病(包括心血管疾病、高血压、高脂血症、糖尿病和抑郁症)的流行风险。

IL-23是一种关键的调节细胞因子,对致病性T辅助17(Th17)细胞的分化、激活和存活至关重要。在银屑病中,IL-23/Th17途径被激活,推动皮肤斑块形成和慢性炎症。一项最近的临床试验表明,通过针对p19亚单位的抗体选择性抑制IL-23产生了与减少皮肤炎症细胞因子表达相关的高而持久的疗效。特异性抑制IL-23可能比生物制剂提供更多的安全益处。IL-17产生细胞,参与粘膜皮肤防御和屏障组织完整性。

Risankizumab是一种人源化IgG1单克隆抗体,与p19亚基有高亲和力,并特异性抑制IL-23。

在本报告中,我们使用来自2个关键的3期随机对照试验(RCT),UltIMMa-1的综合数据,评估了使用risankizumab治疗的中度至重度斑块状银屑病患者与ustekinumab相比绝对PASI阈值的实现和HRQoL的改善。和UltIMMa-2,并使用正在进行的开放标签扩展(OLE)研究LIMMitless的数据评估risankizumab的长期(>52周至172周)疗效。

在重复的随机对照试验UltIMMa-1和UltIMMa-2中,随机分为150 mg risankizumab或45或90 mg ustekinumab的患者的数据被分析,以获得PASI的绝对阈值PASI≤3,PASI≤1和PASI=0,达到这些阈值的时间,并结合PASI和DLQI终点。在开放标签扩展研究LIMMitless中,最初随机接受risankizumab并继续使用risankizumab的患者的数据被分析,以获得绝对PASI水平、平均DLQI评分和DLQI 0/1。

与ustekinumab相比,使用risankizumab治疗的患者比例显着增加,达到PASI≤3,PASI≤1,PASI 0,以及绝对PASI和DLQI([PASI≤3和DLQI≤5] 或[PASI≤1和DLQI 0/1])。首次达到PASI的中位时间≤3,PASI≤1,与ustekinumab治疗的患者相比,risankizumab的PASI=0显着降低。在接受长期risankizumab治疗的患者中,超过90%达到PASI≤3虽然第172周和超过80%达到DLQI 0/1。低绝对PASI评分对应于连续risankizumab治疗第172周的低平均绝对DLQI评分。

表1  基线人口统计和疾病特征

RZB,risankizumab;SD,标准差;BMI,体重指数;PASI,银屑病面积严重程度指数;sPGA,静态医师的全球评估;BSA,体表面积;TNFi,肿瘤坏死因子抑制剂;IL-17i,白细胞介素-17抑制剂。随机分组按重量分层(≤100公斤或>100公斤)和之前的TNFi暴露。b诊断或疑似银屑病关节炎。

 

表2.达到PASI绝对阈值的时间(天)

RZB,risankizumab;UST,ustekinumab;PASI,银屑病面积严重指数

 

通过绝对PASI阈值和患者HRQoL的改善测量,Risankizumab治疗显示出高比率的快速和持久功效。

文献来源:Gooderham M,  Pinter A,  Ferris LK,Long-Term, Durable, Absolute Psoriasis Area and Severity Index and Health-Related Quality of Life Improvements with Risankizumab Treatment: A Post-Hoc Integrated Analysis of Patients with Moderate-to-Severe Plaque Psoriasis.J Eur Acad Dermatol Venereol 2022 Feb 16

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