Department of Dermatology, and Interdisciplinary Center for Inflammatory Diseases, Heidelberg University Hospital, Heidelberg, Germany.
Translational Research in Inflammatory Skin Diseases, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
J Eur Acad Dermatol Venereol. 2023 Oct;37(10):2016-2027. doi: 10.1111/jdv.19236. Epub 2023 Jul 18.
Guselkumab is an interleukin (IL)-23 inhibitor with demonstrated efficacy in patients with psoriasis.
Evaluate the impact of early disease intervention on clinical responses following 28 weeks of guselkumab treatment in patients with moderate-to-severe plaque psoriasis. Correlate clinical response and disease duration data with serum biomarker data.
GUIDE is a phase IIIb randomized, double-blind, parallel-group, multicentre study of adults with moderate-to-severe plaque psoriasis. In study part 1, patients with a short disease duration (SDD [≤2 years]) or a long disease duration (LDD [>2 years]) received guselkumab 100 mg at Week (W) 0, 4, 12, and 20. Those achieving complete skin clearance at W20 and W28 were defined as a super responder (SRe). A multivariable logistic regression analysed the association between baseline factors and the likelihood of becoming an SRe. The relationship between clinical response, disease duration and serum biomarker data was assessed at W0 and 4.
In total, 880 patients were enrolled (SDD/LDD = 40.6%/59.4% of patients). More SDD than LDD patients achieved absolute Psoriasis Area and Severity Index (PASI) = 0 at W28 (51.8% vs. 39.4%) and were SRes (43.7% vs. 28.1% [overall 34.4%]). SDD patients also achieved PASI = 0 quicker than LDD patients (median 141 vs. 200 days). Disease duration and prior biologic use had the greatest impact on becoming an SRe, with no strong association among these independent variables. At baseline, there were no significant differences in the serum biomarker levels of IL-17A, IL-17F, IL-22 and β-defensin 2 between SDD and LDD patients, or between SRe and non-SRe patients. Guselkumab rapidly decreased these markers of systemic inflammation across all patient groups analysed at W4. Guselkumab was well tolerated.
Guselkumab efficacy was consistent across subpopulations, on the skin and systemically. The proportion of SRes was higher in SDD than LDD patients, indicating early treatment intervention may improve clinical outcomes.
古塞库单抗是一种白细胞介素（IL）-23 抑制剂，已证明其在银屑病患者中的疗效。
评估在中重度斑块型银屑病患者接受古塞库单抗治疗 28 周后，早期疾病干预对临床反应的影响。将临床反应和疾病持续时间数据与血清生物标志物数据相关联。
GUIDE 是一项 IIIb 期随机、双盲、平行分组、多中心研究，纳入了中重度斑块型银屑病的成年患者。在研究部分 1 中，疾病持续时间较短（SDD [≤2 年]）或较长（LDD [>2 年]）的患者在第 0、4、12 和 20 周接受古塞库单抗 100mg 治疗。在第 20 和 28 周实现完全皮肤清除的患者被定义为超级应答者（SRe）。多变量逻辑回归分析了基线因素与成为 SRe 的可能性之间的关系。在 W0 和 4 时评估了临床反应、疾病持续时间和血清生物标志物数据之间的关系。
共纳入 880 例患者（SDD/LDD[患者的 40.6%/59.4%]）。与 LDD 患者相比，更多的 SDD 患者在 W28 时达到绝对银屑病面积和严重性指数（PASI）=0（51.8%比 39.4%），且为 SRe（43.7%比 28.1%[总体为 34.4%]）。SDD 患者达到 PASI=0 的时间也快于 LDD 患者（中位数 141 比 200 天）。疾病持续时间和既往生物制剂使用对成为 SRe 的影响最大，这些独立变量之间没有很强的关联。在基线时，SDD 和 LDD 患者之间，或 SRe 和非 SRe 患者之间，IL-17A、IL-17F、IL-22 和β-防御素 2 的血清生物标志物水平没有显著差异。古塞库单抗在分析的所有患者组中，在 W4 时迅速降低了这些全身炎症标志物。古塞库单抗具有良好的耐受性。
古塞库单抗在亚人群、皮肤和全身的疗效一致。与 LDD 患者相比，SDD 患者中 SRe 的比例更高，表明早期治疗干预可能改善临床结局。
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