Monotherapy with Biologics for Generalized Pustular Psoriasis: A Systematic Review of Comparative Interventional Studies with an Exploratory Network Meta-Analysis.

Background-Generalized pustular psoriasis (GPP) is a rare and severe inflammatory skin disorder-and evidence regarding relative impact of treatments thereof is currently scant. Objective-We aimed to systematically review and narratively synthesize comparative interventional therapies for GPP and secondarily explore their relative effectiveness through exploratory network meta-analyses (NMAs). Methods-Comprehensive searches were performed in PubMed and EMBASE to identify comparative interventional studies that investigated the impact of biologics in GPP. Bayesian NMAs were conducted only for exploratory analyses. Results-Eleven studies met our inclusion criteria and data from 4 of the 11 were used for NMAs. Methodological heterogeneity was evident; the various biologics demonstrated effectiveness in treating GPP. Inhibitors of interleukin (IL)-36 (e.g., spesolimab) resulted in rapid pustular clearance within one week and sustained reductions in flare occurrence. Inhibitors targeting IL-17, IL-23, TNF, and IL-12/23 also demonstrated high response rates, durable disease control, and improvements in quality of life among diverse patient populations. Results from our exploratory NMAs revealed patterns of relative effectiveness with IL-17 and IL-36 inhibitors that are consistent with the existing literature. However, methodological limitations across the four studies deterred us from making conclusive inferences. Conclusions-Biologic therapies provide significant clinical benefit in patients with GPP. Our narrative syntheses highlight the need for future quantitative syntheses.