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

Abstract Background 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. Objectives To evaluate the efficacy and safety of guselkumab in paediatric patients with moderate-to-severe plaque psoriasis (PROTOSTAR; NCT03451851). Methods 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). 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 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. Conclusions 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.