Prajapati Vimal H, Seyger Marieke M B, Wilsmann-Theis Dagmar, Szakos Erzsebet, Kaszuba Andrzej, van Hartingsveldt Bart, Jett Meg, Jiang Gigi, Li Shu, Sinha Vikash, Crauwels Herta, DeKlotz Cynthia M C, Paller Amy S
Dermatology Research Institute, Calgary, AB, Canada.
Probity Medical Research, Calgary, AB, Canada.
Br J Dermatol. 2025 Mar 18;192(4):618-628. doi: 10.1093/bjd/ljae502.
No currently approved treatment for paediatric plaque psoriasis selectively targets interleukin (IL)-23. In adults, guselkumab (a selective IL-23 inhibitor that targets the p19 subunit) demonstrated substantial efficacy with a favourable safety profile in treating moderate-to-severe plaque psoriasis.
To evaluate the efficacy and safety of guselkumab in paediatric patients with moderate-to-severe plaque psoriasis (PROTOSTAR; NCT03451851).
This phase III randomized placebo-controlled study enrolled patients aged ≥ 6 to < 18 years with moderate-to-severe plaque psoriasis. In part 1 [week (W)0-W16], patients were randomized to receive guselkumab, placebo or open-label etanercept (active reference arm). At W16, part 1 patients entered a guselkumab withdrawal/retreatment period or continued/crossed over to receive guselkumab (W16-W52). Co-primary endpoints were Investigator Global Assessment (IGA) 0/1 and ≥ 75% improvement in Psoriasis Area and Severity Index (PASI 75) [or U.S. Food and Drug Administration-required ≥ 90% improvement in PASI (PASI 90) co-primary endpoint] responses at W16 of part 1. Part 2 evaluated continuous open-label guselkumab treatment (W0-W52).
Of 92 and 28 patients enrolled in parts 1 and 2, respectively, 86% and 96% continued treatment through W52. In part 1, at W16, significantly higher proportions of guselkumab-treated compared with placebo-treated patients achieved IGA 0/1 (66% vs. 16%; P < 0.001), PASI 75 (76% vs. 20%; P < 0.001) and PASI 90 (56% vs. 16%; P < 0.01). More than one-third of guselkumab-treated patients achieved clear skin [IGA 0: 39% vs. 4% placebo; 100% improvement in PASI (PASI 100): 34% vs. 0% placebo; both P < 0.01]. In part 2, at W52, 86%, 93% and 82% of guselkumab-treated patients achieved IGA 0/1, PASI 75 and PASI 90, respectively. Through W16 of part 1, 42%, 68% and 58% of guselkumab-, placebo- and etanercept-treated patients, respectively, experienced adverse events (AEs). Rates of AEs with guselkumab were similar through W52 in parts 1 and 2; common AEs included nasopharyngitis, upper respiratory tract infection and COVID-19. No serious or opportunistic infections occurred.
Guselkumab demonstrated significant and clinically meaningful responses in paediatric patients with moderate-to-severe plaque psoriasis, and all co-primary and major secondary endpoints were met. Safety outcomes for guselkumab in paediatric patients were similar to placebo and consistent with the established profile in adults, with no new safety signals identified. These findings support the use of guselkumab to treat paediatric patients with moderate-to-severe plaque psoriasis.
目前尚无获批用于治疗儿童斑块状银屑病的疗法能选择性靶向白细胞介素（IL）-23。在成人中，古塞库单抗（一种靶向p19亚基的选择性IL-23抑制剂）在治疗中度至重度斑块状银屑病方面显示出显著疗效且安全性良好。
评估古塞库单抗在中度至重度斑块状银屑病儿童患者中的疗效和安全性（PROTOSTAR；NCT03451851）。
这项III期随机安慰剂对照研究纳入了年龄≥6至<18岁的中度至重度斑块状银屑病患者。在第1部分（第0周-第16周），患者被随机分配接受古塞库单抗、安慰剂或开放标签的依那西普（活性对照组）。在第16周时，第1部分的患者进入古塞库单抗撤药/再治疗期，或继续/交叉接受古塞库单抗治疗（第16周-第52周）。共同主要终点为第1部分第16周时研究者整体评估（IGA）为0/1以及银屑病面积和严重程度指数改善≥75%（PASI 75）[或美国食品药品监督管理局要求的PASI改善≥90%（PASI 90）共同主要终点]反应。第2部分评估持续开放标签的古塞库单抗治疗（第0周-第52周）。
第1部分和第2部分分别纳入92例和28例患者，86%和96%的患者持续治疗至第52周。在第1部分，第16周时，与接受安慰剂治疗的患者相比，接受古塞库单抗治疗的患者达到IGA 0/1（66%对16%；P<0.001）、PASI 75（76%对20%；P<0.001）和PASI 90（56%对16%；P<0.01）的比例显著更高。超过三分之一接受古塞库单抗治疗的患者实现了皮肤清除[IGA 0：39%对安慰剂组的4%；PASI改善100%（PASI 100）：34%对安慰剂组的0%；P均<0.01]。在第2部分，第52周时，接受古塞库单抗治疗的患者中分别有86%、93%和82%达到IGA 0/1、PASI 75和PASI 90。在第1部分的第16周期间，接受古塞库单抗、安慰剂和依那西普治疗的患者分别有42%、68%和58%发生不良事件（AE）。在第1部分和第2部分中，至第52周时，古塞库单抗治疗的AE发生率相似；常见AE包括鼻咽炎、上呼吸道感染和新型冠状病毒肺炎。未发生严重或机会性感染。
古塞库单抗在中度至重度斑块状银屑病儿童患者中显示出显著且具有临床意义的反应，所有共同主要终点和主要次要终点均达到。古塞库单抗在儿童患者中的安全性结果与安慰剂相似，且与成人中已确立的情况一致，未发现新的安全信号。这些发现支持使用古塞库单抗治疗中度至重度斑块状银屑病儿童患者。
