Real-world efficacy of biologics may be insufficiently assessed through common drug survival studies. The objective was thus to examine real-world performance of biologics in the treatment of psoriasis using the composite endpoint of either discontinuation or off-label dose escalation. Using a prospective nationwide registry (DERMBIO, 2007-2019), we included psoriasis patients treated with adalimumab, secukinumab, and/or ustekinumab, which have all been used as first-line therapy during the inclusion period. The primary endpoint was a composite of either off-label dose escalation or discontinuation of treatment, while the secondary outcomes were dose escalation and discontinuation, respectively. Kaplan-Meier curves were used for the presentation of unadjusted drug survival curves. Cox-regression models were used for risk assessment. In 4313 treatment series (38.8% women, mean age 46.0 years, and 58.3% bio-naivety) we found that the risk of the composite endpoint was lower for secukinumab when compared with ustekinumab (hazard ratio [HR] 0.66, 95% confidence interval (CI) 0.59-0.76), but higher for adalimumab (HR 1.15, 95% CI 1.05-1.26). However, the risk of discontinuation was higher for secukinumab (HR 1.24, 95% CI 1.08-1.42) and adalimumab (HR 2.01, 95% CI 1.82-2.22). For bio-naive patients treated with secukinumab, the risk of discontinuation was comparable to ustekinumab (HR 0.95, 95% CI 0.61-1.49).