Psoriasis im Kindes- und Jugendalter: Zwischen Off-Label-Therapie und Zulassung

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.