BioDrugs. 2026 Jul 2. doi: 10.1007/s40259-026-00795-9. Online ahead of print.
ABSTRACT
BACKGROUND: Ustekinumab biosimilars have expanded treatment options for moderate-to-severe plaque psoriasis, but pooled evidence is needed to determine whether they achieve therapeutic equivalence to reference ustekinumab during the initial randomized comparative period before protocol-defined switching.
OBJECTIVES: The aim of this systematic review was to assess the therapeutic equivalence of ustekinumab biosimilars versus reference ustekinumab during the pre-switch period in adults with moderate-to-severe plaque psoriasis.
METHODS: We searched PubMed, Embase, Scopus, Web of Science, Cochrane Central Register of Controlled Trials (CENTRAL), and trial registries from inception to 15 October 2025 for phase III randomized clinical trials comparing ustekinumab biosimilars or follow-on biologics with reference ustekinumab and reporting comparative data before switching. Data were extracted independently by two reviewers. Risk of bias was assessed using the Risk of Bias 2 (RoB 2) tool, and certainty of evidence was assessed using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach. Random-effects meta-analysis with Hartung-Knapp-Sidik-Jonkman 95% confidence intervals (CIs) was performed. The primary outcome was 75% improvement in Psoriasis Area and Severity Index (PASI 75) response at week 12, analyzed using risk differences with a prespecified equivalence margin of ± 10%.
RESULTS: Nine randomized trials including 4532 participants were analyzed. At week 12, the pooled risk difference for PASI 75 was 0.02 (95% CI -0.02 to 0.05), meeting the prespecified ± 10% equivalence criterion, with low between-study heterogeneity (I2 statistic = 6%). Equivalence-consistent estimates were also observed for PASI 90 (risk difference – 0.01, 95% CI – 0.06 to 0.03) and PASI 100 (risk difference 0.00, 95% CI – 0.03 to 0.03). Treatment-emergent adverse events were comparable through week 28 (risk difference 0.01, 95% CI – 0.04 to 0.06). At week 12, anti-drug antibody detection was lower in biosimilar arms (risk difference – 0.14, 95% CI – 0.23 to – 0.04), which may partly reflect assay variability rather than clinically meaningful differences. No material differences were observed in short-term pre-switch clinical response, patient-reported quality of life, or safety.
CONCLUSIONS: During the initial randomized comparative period, ustekinumab biosimilars met prespecified therapeutic equivalence criteria for PASI 75 and showed equivalence-consistent results for PASI 90 and PASI 100, with comparable short-term safety versus reference ustekinumab. These findings provide pooled reassurance across standard and stringent skin-clearance outcomes during a clinically relevant early treatment window.
REGISTRATION: PROSPERO (CRD420251166323). Registered October 12, 2025.
PMID:42393486 | DOI:10.1007/s40259-026-00795-9
