BACKGROUND/OBJECTIVES: Australian data comparing biologic treatments for moderate to severe chronic plaque psoriasis are lacking. We compared persistence on therapy across four biologic therapies (adalimumab, guselkumab, secukinumab and ustekinumab) used to treat chronic plaque psoriasis. The impact of prior biologic use on persistence was also investigated. METHODS: This retrospective cohort analysis of the Pharmaceutical Benefits Scheme (PBS) 10% sample included data from adult patients prescribed ≥1 biologic of interest by a dermatologist from 1 September 2015 to 31 December 2021. Persistence was defined as continued use until 180 days without a prescription. The index date was the date of the first claim of the biologic. Persistence was evaluated using Kaplan-Meier methods, log-rank tests, adjusted analyses using Cox's regressions, and propensity score matching. RESULTS: In total, 878 patients, with 1131 index prescriptions, were included. Guselkumab median persistence was not reached in the study period (PBS listed from February 2019). In the adjusted analysis, persistence to guselkumab was significantly greater than to adalimumab (n = 105; median 16 months, HR 2.71 (95% CI 1.94-3.8), p < 0.001), ustekinumab (n = 336; median 19 months, HR 2.91 (95% CI 2.22-3.82), p < 0.001) and secukinumab (n = 305; median 30 months, HR 1.8 (95% CI 1.36-2.38), p < 0.001). Bio-naïve patients had longer persistence on treatment than bio-experienced patients. CONCLUSIONS: The nationally representative PBS dataset can provide real-world insights into the persistence on biologic therapies for psoriasis in Australia, where eligibility criteria for reimbursed treatment are stringent. Persistence is an indirect marker of sustained treatment effectiveness and tolerability. Both unadjusted and adjusted analyses found longer persistence for guselkumab compared to adalimumab, secukinumab or ustekinumab.