Blauvelt Andrew, Pariser David M, Tyring Stephen, Bagel Jerry, Alexis Andrew F, Soung Jennifer, Armstrong April W, Muscianisi Elisa, Kianifard Farid, Steadman Jennifer, Sarkar Rajendra Prasad, Garcet Sandra, Krueger James G
Oregon Medical Research Center, Portland, OR, USA.
Department of Dermatology, Eastern Virginia Medical School, Norfolk, VA, USA.
J Dermatol Sci. 2023 Jan;109(1):12-21. doi: 10.1016/j.jdermsci.2023.01.003. Epub 2023 Jan 9.
The IL-17A inhibitor secukinumab has demonstrated consistent efficacy and safety in patients with moderate-to-severe plaque psoriasis, with normalization of molecular and histopathologic psoriasis markers.
To investigate treatment effects of secukinumab on clinical signs and psoriatic inflammation markers over 52 weeks in patients with psoriasis.
In the ObePso-S study (NCT03055494), patients with psoriasis were randomized 2:1 to receive secukinumab 300 mg (n = 54) or placebo (n = 28), stratified by body weight (<90 or ≥90 kg), for 52 weeks. At Week 12, patients receiving placebo were switched to secukinumab. Psoriasis Area and Severity Index improvement of 90% (PASI90) and Investigator's Global Assessment modified 2011 0/1 responses were assessed at Weeks 12 and 52. Immunohistochemistry for keratin 16 (K16) and gene expression profiles were evaluated in lesional and non-lesional skin biopsies collected at baseline, Week 12, and Week 52.
Of patients receiving secukinumab, 55.8% and 59.6% achieved PASI90 at Weeks 12 and 52, respectively. K16 was absent in 93.1% of Week 12 PASI90 responders and 93.6% of Week 52 PASI90 responders, which mirrored the down-regulated expression of psoriatic inflammation. Week 52 PASI90 non-responders experienced regression of clinical and inflammatory marker responses toward baseline levels. Lower control of inflammatory gene expression at Week 12 was associated with suboptimal clinical responses at Week 52.
Sustained clinical responses with secukinumab were associated with rapid and sustained normalization of K16 and inflammatory gene expression in most patients. Molecular anti-inflammatory effects of secukinumab at Week 12 were associated with clinical responses at Week 52.
白细胞介素-17A抑制剂司库奇尤单抗在中度至重度斑块状银屑病患者中已显示出持续的疗效和安全性，银屑病的分子和组织病理学标志物恢复正常。
研究司库奇尤单抗在52周内对银屑病患者临床症状和银屑病炎症标志物的治疗效果。
在ObePso-S研究（NCT03055494）中，银屑病患者按体重（<90或≥90 kg）分层，以2:1的比例随机接受司库奇尤单抗300 mg（n = 54）或安慰剂（n = 28）治疗52周。在第12周时，接受安慰剂治疗的患者换用司库奇尤单抗。在第12周和第52周评估银屑病面积和严重程度指数改善90%（PASI90）以及2011年改良的研究者整体评估0/1反应。在基线、第12周和第52周采集的皮损和非皮损皮肤活检样本中，对角蛋白16（K16）进行免疫组织化学检测并评估基因表达谱。
接受司库奇尤单抗治疗的患者中，分别有55.8%和59.6%在第12周和第52周达到PASI90。在第12周达到PASI90的患者中有93.1%以及在第52周达到PASI9日的患者中有93.6%的K16呈阴性，这反映了银屑病炎症表达的下调。第52周未达到PASI90的患者临床和炎症标志物反应向基线水平回归。第12周炎症基因表达控制较差与第52周临床反应欠佳相关。
司库奇尤单抗持续的临床反应与大多数患者K16和炎症基因表达迅速且持续恢复正常有关。司库奇尤单抗在第12周的分子抗炎作用与第52周的临床反应相关。
