Blauvelt A, Leonardi C, Elewski B, Crowley J J, Guenther L C, Gooderham M, Langley R G, Vender R, Pinter A, Griffiths C E M, Tada Y, Elmaraghy H, Lima R G, Gallo G, Renda L, Burge R, Park S Y, Zhu B, Papp K
Oregon Medical Research Center, Portland, OR, USA.
Central Dermatology, St Louis, MO, USA.
Br J Dermatol. 2021 Jun;184(6):1047-1058. doi: 10.1111/bjd.19509. Epub 2020 Oct 25.
Significantly more patients with moderate-to-severe plaque psoriasis treated with the interleukin (IL)-17A inhibitor ixekizumab vs. the IL-23p19 inhibitor guselkumab in the IXORA-R head-to-head trial achieved 100% improvement in Psoriasis Area and Severity Index (PASI 100) at week 12.
To compare skin and nail clearance and patient-reported outcomes for ixekizumab vs. guselkumab, up to week 24.
IXORA-R enrolled adults with moderate-to-severe plaque psoriasis, defined as static Physician's Global Assessment ≥ 3, PASI ≥ 12 and involved body surface area ≥ 10%. Statistical comparisons were performed using the Cochran-Mantel-Haenszel test stratified by pooled site. Time-to-first-event comparisons were performed using Kaplan-Meier analysis, and P-values were generated using adjusted log-rank tests stratified by treatment group. Cumulative days at clinical and patient-reported responses were compared by ancova. The trial was registered with ClinicalTrials.gov (NCT03573323).
Of the 1027 patients randomly assigned, 90% completed the trial (465 of 520 ixekizumab and 459 of 507 guselkumab). As early as week 2 and through week 16, more patients on ixekizumab achieved PASI 100 (P < 0·01). At week 24, ixekizumab was noninferior to guselkumab (50% vs. 52%, difference -2·3%), with no statistically significant difference in PASI 100 (P = 0·41). More patients receiving ixekizumab showed completely clear nails at week 24 (52% vs. 31%, P = 0·007). The median time to first PASI 50/75/90 and PASI 100 were 2 and 7·5 weeks shorter, respectively, for patients on ixekizumab vs. guselkumab (P < 0·001). Patients on ixekizumab also had a greater cumulative benefit, with more days at PASI 90 and 100, with Dermatology Life Quality Index of 0 or 1, and itch free (P < 0·05). The frequency of serious adverse events was 3% for each group, with no new safety signals.
Ixekizumab was noninferior to guselkumab in complete skin clearance and superior in clearing nails at week 24. Ixekizumab cleared skin more rapidly in patients with moderate-to-severe plaque psoriasis, with a greater cumulative benefit, than guselkumab. Overall, the safety findings were consistent with the known safety profile for ixekizumab.
在IXORA-R头对头试验中，与白细胞介素（IL）-23p19抑制剂古塞库单抗相比，接受IL-17A抑制剂司库奇尤单抗治疗的中重度斑块状银屑病患者在第12周时达到银屑病面积和严重程度指数（PASI 100）改善100%的比例显著更高。
比较司库奇尤单抗与古塞库单抗在第24周时的皮肤和指甲清除情况以及患者报告的结局。
IXORA-R纳入了中重度斑块状银屑病成人患者，定义为静态医师整体评估≥3、PASI≥12且体表面积累及≥10%。使用按合并研究中心分层的 Cochr an-Mantel-Haenszel检验进行统计学比较。使用Kaplan-Meier分析进行首次事件发生时间比较，并使用按治疗组分层的调整对数秩检验生成P值。通过协方差分析比较临床和患者报告反应的累积天数。该试验已在ClinicalTrials.gov注册（NCT03573323）。
在随机分配的1027例患者中，90%完成了试验（司库奇尤单抗组520例中的465例，古塞库单抗组507例中的459例）。早在第2周直至第16周，接受司库奇尤单抗治疗的患者达到PASI 100的比例更高（P<0.01）。在第24周时，司库奇尤单抗不劣于古塞库单抗（50%对52%，差值-2.3%），PASI 100无统计学显著差异（P=0.41）。在第24周时，接受司库奇尤单抗治疗的患者中指甲完全清除的比例更高（52%对31%，P=0.007）。与接受古塞库单抗治疗的患者相比，接受司库奇尤单抗治疗的患者首次达到PASI 50/75/90和PASI 100的中位时间分别短2周和7.5周（P<0.001）。接受司库奇尤单抗治疗的患者也有更大的累积获益，达到PASI 90和100、皮肤病生活质量指数为0或1以及无瘙痒的天数更多（P<0.05）。每组严重不良事件的发生率均为3%，未发现新的安全信号。
在第24周时，司库奇尤单抗在完全清除皮肤方面不劣于古塞库单抗，在清除指甲方面更优。与古塞库单抗相比，司库奇尤单抗在中重度斑块状银屑病患者中更快速地清除皮肤，且累积获益更大。总体而言，安全性结果与司库奇尤单抗已知的安全性特征一致。
