Guselkumab for the treatment of moderate-to-severe plaque psoriasis in pediatric patients: results of the phase 3, randomized, placebo-controlled PROTOSTAR study.
Vimal H Prajapati, Marieke M B Seyger, Dagmar Wilsmann-Theis, Erzsebet Szakos, Andrzej Kaszuba, Bart van Hartingsveldt, Meg Jett, Gigi Jiang, Shu Li, Vikash Sinha, Herta Crauwels, Cynthia M C DeKlotz, Amy S Paller
{"title":"Guselkumab for the treatment of moderate-to-severe plaque psoriasis in pediatric patients: results of the phase 3, randomized, placebo-controlled PROTOSTAR study.","authors":"Vimal H Prajapati, Marieke M B Seyger, Dagmar Wilsmann-Theis, Erzsebet Szakos, Andrzej Kaszuba, Bart van Hartingsveldt, Meg Jett, Gigi Jiang, Shu Li, Vikash Sinha, Herta Crauwels, Cynthia M C DeKlotz, Amy S Paller","doi":"10.1093/bjd/ljae502","DOIUrl":null,"url":null,"abstract":"<p><strong>Background: </strong>No currently approved treatment for pediatric plaque psoriasis selectively targets interleukin (IL)-23. In adults, guselkumab (a selective IL-23 inhibitor targeting the p19 subunit) demonstrated substantial efficacy with a favorable safety profile in treating moderate-to-severe plaque psoriasis.</p><p><strong>Objective: </strong>PROTOSTAR (NCT03451851) evaluated the efficacy and safety of guselkumab in pediatric patients with moderate-to-severe plaque psoriasis.</p><p><strong>Methods: </strong>This phase 3, randomized, placebo-controlled study enrolled patients ≥6 to <18 years of age 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's Global Assessment (IGA) 0/1 and Psoriasis Area and Severity Index (PASI)75 (or United States Food and Drug Administration-required PASI90 co-primary endpoint) responses at W16 of Part 1. Part 2 evaluated continuous open-label guselkumab treatment (W0-W52).</p><p><strong>Results: </strong>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 than placebo-treated patients achieved IGA 0/1 (66% vs 16%; P<0.001), PASI75 (76% vs 20%; P<0.001), and PASI90 (56% vs 16%; P<0.01). More than one-third of guselkumab-treated patients achieved clear skin (IGA 0: 39% vs 4% placebo; PASI100: 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, PASI75, and PASI90, respectively. Through W16 of Part 1, 42%, 68%, and 58% of guselkumab-, placebo-, and etanercept-treated patients, respectively, had 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.</p><p><strong>Conclusions: </strong>Guselkumab demonstrated significant and clinically meaningful responses in pediatric patients with moderate-to-severe plaque psoriasis and all co-primary and major secondary endpoints were met. Guselkumab safety outcomes were similar to placebo; no new safety signals were identified. These findings support the use of guselkumab to treat pediatric patients with moderate-to-severe plaque psoriasis.</p>","PeriodicalId":9238,"journal":{"name":"British Journal of Dermatology","volume":" ","pages":""},"PeriodicalIF":11.0000,"publicationDate":"2024-12-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"British Journal of Dermatology","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1093/bjd/ljae502","RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"DERMATOLOGY","Score":null,"Total":0}
引用次数: 0
Abstract
Background: No currently approved treatment for pediatric plaque psoriasis selectively targets interleukin (IL)-23. In adults, guselkumab (a selective IL-23 inhibitor targeting the p19 subunit) demonstrated substantial efficacy with a favorable safety profile in treating moderate-to-severe plaque psoriasis.
Objective: PROTOSTAR (NCT03451851) evaluated the efficacy and safety of guselkumab in pediatric patients with moderate-to-severe plaque psoriasis.
Methods: This phase 3, randomized, placebo-controlled study enrolled patients ≥6 to <18 years of age 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's Global Assessment (IGA) 0/1 and Psoriasis Area and Severity Index (PASI)75 (or United States Food and Drug Administration-required PASI90 co-primary endpoint) responses at W16 of Part 1. Part 2 evaluated continuous open-label guselkumab treatment (W0-W52).
Results: 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 than placebo-treated patients achieved IGA 0/1 (66% vs 16%; P<0.001), PASI75 (76% vs 20%; P<0.001), and PASI90 (56% vs 16%; P<0.01). More than one-third of guselkumab-treated patients achieved clear skin (IGA 0: 39% vs 4% placebo; PASI100: 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, PASI75, and PASI90, respectively. Through W16 of Part 1, 42%, 68%, and 58% of guselkumab-, placebo-, and etanercept-treated patients, respectively, had 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.
Conclusions: Guselkumab demonstrated significant and clinically meaningful responses in pediatric patients with moderate-to-severe plaque psoriasis and all co-primary and major secondary endpoints were met. Guselkumab safety outcomes were similar to placebo; no new safety signals were identified. These findings support the use of guselkumab to treat pediatric patients with moderate-to-severe plaque psoriasis.
期刊介绍:
The British Journal of Dermatology (BJD) is committed to publishing the highest quality dermatological research. Through its publications, the journal seeks to advance the understanding, management, and treatment of skin diseases, ultimately aiming to improve patient outcomes.