Guselkumab for the treatment of moderate-to-severe plaque psoriasis in pediatric patients: results of the phase 3, randomized, placebo-controlled PROTOSTAR study

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.