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Summary: Background: 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. Objectives: To compare skin and nail clearance and patient‐reported outcomes for ixekizumab vs. guselkumab, up to week 24. Methods: 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). Results: 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. Conclusions: 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. What is already known about this topic?Patients with plaque psoriasis desire both high levels of clearance and rapid onset of treatment effects.Ixekizumab is a high‐affinity monoclonal antibody that selectively targets interleukin (IL)‐17A.In the 12‐week report of the IXORA‐R study, ixekizumab demonstrated significantly higher efficacy at early timepoints than the IL‐23p19 inhibitor guselkumab, with more patients achieving 100% improvement in Psoriasis Area and Severity Index (PASI 100) and improved quality of life as early as week 4. What does this study add?Patients on ixekizumab vs. guselkumab achieved similar levels of skin clearance and superior efficacy in the resolution of nail psoriasis at week 24.Patients on ixekizumab vs. guselkumab had a greater cumulative benefit, with more days at PASI 90 and 100, more days when psoriasis did not impact their quality of life, and more itch‐free days.The safety profiles of both drugs were consistent with those in previous studies. Linked Comment: Puig. Br J Dermatol 2021; 184:992–993. [ABSTRACT FROM AUTHOR]

Summary: Background: Patients with psoriasis value rapid and complete skin clearance. No head‐to‐head studies have focused on early responses to interleukin (IL)‐17 vs. IL‐23 inhibitors. Objectives: To compare early and complete skin clearance by the IL‐17A inhibitor ixekizumab vs. the IL‐23p19 inhibitor guselkumab. Methods: IXORA‐R, a 24‐week, randomized, double‐blinded study, enrolled adults with moderate‐to‐severe plaque psoriasis [static Physician's Global Assessment of Disease (sPGA) score of ≥ 3, Psoriasis Area and Severity Index (PASI) ≥ 12, and ≥ 10% body surface area]. Patients were randomized (1 : 1) to receive the approved dose of subcutaneous ixekizumab or guselkumab. Primary end point was 100% improvement in PASI (PASI 100) at week 12. Major secondary end points included other levels of improved PASI and sPGA at different time points. Comparisons were made using the Cochran–Mantel–Haenszel test with a multiple testing strategy. Nonresponder imputation was used for missing data. After the completion of the study, the final secondary end point (PASI 100 at 24 weeks) and safety data through week 24 will be reported. Results: In total, 1027 patients were randomized. The primary end point PASI 100 at week 12 was met [215/520 ixekizumab (41%); 126/507 guselkumab (25%); P < 0·001]. All major secondary end points measured up to week 12 were met, including PASI 50 at week 1 and PASI 75 at week 2. Serious adverse event frequency was 3% for each group; no new safety signals were identified. Conclusions: Ixekizumab was superior to guselkumab for rapidly improving signs and symptoms in patients with moderate‐to‐severe plaque psoriasis by week 12. Adverse events were similar to previous ixekizumab and guselkumab studies. Compared with the IL‐23 inhibitor guselkumab, ixekizumab can offer complete skin clearance more rapidly to patients with moderate‐to‐severe plaque psoriasis. What's already known about this topic? Patients with plaque psoriasis desire both high levels of clearance and rapid onset of treatment effects.Ixekizumab, a high‐affinity monoclonal antibody that selectively targets interleukin (IL)‐17A, has demonstrated greater and faster skin clearance than etanercept and ustekinumab, with consistent long‐term efficacy, safety and durability of response.Clinical trial data and systematic reviews have suggested that IL‐17 inhibitors can improve a patient's psoriasis more rapidly than IL‐23 inhibitors. What does this study add? The head‐to‐head study design directly compares the efficacy and speed of response of ixekizumab and the IL‐23 inhibitor guselkumab in moderate‐to‐severe plaque psoriasis.The primary end point was met, showing superiority of ixekizumab over guselkumab for achieving complete skin clearance at week 12.The safety profile of ixekizumab was consistent with previous studies.Ixekizumab can deliver patients complete skin clearance and improved quality of life more rapidly than guselkumab. Linked Comment:Veysey. Br J Dermatol 2020; 182:1321–1322. Plain language summary available online [ABSTRACT FROM AUTHOR]

Summary: 银屑病是一种皮肤病,会导致全身皮肤出现红色、鳞屑和瘙痒的斑块。 它影响着全球约 1.25 亿人。除了导致生活质量下降外,更广泛的银屑病往往会影响内在健康。过去几年开发的新药经常可以帮助银屑病患者实现完全清除皮损,并改善整体健康状况。 其中两种药物是 ixekizumab (IXE) 和 guselkumab (GUS)。然而,IXE 和 GUS 的工作方式不同,之前的一些研究表明,IXE 可能比 GUS 起效更快。 在这项研究中,来自美国和加拿大的研究人员对这些药物进行了直接对比测试,测量了开始用药后头 12 周的清除速度和皮肤完全清除率。 这项研究中的人接受了 IXE 或 GUS。12 周后,接受 IXE 治疗的人皮损完全清除者所占比例比接受 GUS 治疗的人高 16%(使用 IXE 的人为 41%,使用 GUS 的人为 25%)。 无论使用一周后皮肤清除率达 50% 的人数,还是使用两周后皮肤清除率达 75% 的人数,IXE 都比 GUS 多。与 GUS 相比,IXE 对瘙痒、皮肤疼痛和生活质量的改善也更快。IXE 和 GUS 出现严重副作用的患者数量相似。 总体而言,与使用 GUS 的患者相比,使用 IXE 的银屑病患者皮肤清除干净的速度更快,也更为迅速感觉好转。 本摘要涉及研究: 来自一项随机分配、双盲试验的 Ixekizumab 与 Guselkumab 治疗中度至重度斑块型银屑病患者的直接比较: 12 周疗效、安全性和应答速度 Linked Article: Blauvelt et al. Br J Dermatol 2020; 182:1348–1358 [ABSTRACT FROM AUTHOR]

Summary: Psoriasis is a skin disease that causes red, scaly and itchy patches of skin all over the body. It affects about 125 million people worldwide. As well as causing decreased quality of life, more widespread psoriasis often affects internal health. New drugs developed in the last few years often help people with psoriasis to achieve completely clear skin, and improve overall health. Two of these drugs are ixekizumab (IXE) and guselkumab (GUS). IXE and GUS work in different ways, however, and some prior research showed that IXE may work faster than GUS. In this study, researchers from the U.S.A. and Canada tested these drugs head‐to‐head, measuring speed of clearance and complete skin clearance rates over the first 12 weeks after starting drug. People in this study received either IXE or GUS. After 12 weeks, completely clear skin was achieved by 16% more people if they were treated with IXE compared to GUS (41% of people who took IXE versus 25% of people who took GUS). More people on IXE than GUS had 50% clearer skin after just one week and 75% clearer skin after two weeks. Itching, skin pain, and quality of life also improved faster with IXE compared to GUS. The number of patients with serious side effects was similar for IXE and GUS. Overall, people with psoriasis who take IXE may get clear skin faster and feel better more quickly than people who take GUS. This is a summary of the study: A head‐to‐head comparison of ixekizumab vs. guselkumab in patients with moderate‐to‐severe plaque psoriasis: 12‐week efficacy, safety and speed of response from a randomized, double‐blinded trial Linked Article: Blauvelt et al. Br J Dermatol 2020; 182:1348–1358 [ABSTRACT FROM AUTHOR]