Short-term efficacy and safety of guselkumab for moderate-to-severe plaque psoriasis: a systematic review and meta-analysis with a pasi response-depth analysis

To systematically evaluate the short-term efficacy and safety of guselkumab in moderate-to-severe plaque psoriasis and to explore whether its comparative advantage over adalimumab changes across increasingly stringent PASI response thresholds. PubMed, Embase, Web of Science, China National Knowledge Infrastructure (CNKI), and Wanfang Data were systematically searched from inception to April 2026 for randomized controlled trials (RCTs) evaluating guselkumab in moderate-to-severe plaque psoriasis. Two reviewers independently screened the literature, extracted data, and assessed methodological quality using the Cochrane RoB 2.0 tool. Meta-analysis was performed using RevMan 5.3. All efficacy and safety data were extracted at Week 16. In a post hoc exploratory response-depth analysis of the three head-to-head trials, the relative treatment effect of guselkumab versus adalimumab was examined across PASI75, PASI90, and PASI100 thresholds. Six RCTs comprising 997 patients in the guselkumab group, 625 in the adalimumab group, and 548 in the placebo group were included. At Week 16, guselkumab was associated with a significantly higher PASI90 response rate than adalimumab (RR = 1.48, 95% CI: 1.35–1.62, P < 0.001) and placebo (RR = 28.29, 95% CI: 16.69–47.96, P < 0.001). The exploratory head-to-head response-depth analysis showed a progressive increase in the relative advantage of guselkumab as the PASI target became more stringent: RR = 1.25 (95% CI: 1.18–1.32) for PASI75, 1.48 (1.35–1.62) for PASI90, and 1.85 (1.54–2.23) for PASI100. Corresponding crude response proportions across the three direct-comparison trials were 87.8% versus 71.0%, 70.8% versus 48.2%, and 35.3% versus 19.0%, respectively. Most short-term safety comparisons were imprecise and did not reach statistical significance. For upper respiratory tract infection versus adalimumab, the pooled estimate was RR = 1.69 (95% CI: 0.99–2.87; P = 0.05) based on two trials; the confidence interval only narrowly included the null and the comparison was underpowered. Beyond confirming greater Week 16 efficacy of guselkumab, this meta-analysis suggests that its relative advantage over adalimumab becomes more pronounced as the treatment target shifts from PASI75 toward near-complete or complete skin clearance. This response-depth pattern may be clinically relevant in an era in which PASI90 and PASI100 are increasingly used as treatment goals. Most evaluated short-term safety outcomes did not show statistically significant differences; however, estimates were imprecise and should not be interpreted as evidence of equivalence.