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Psoriasis is an immunodysregulatory inflammatory disease associated with comorbidities affecting quality of life. With the advent of new treatments, there is growing need to assess the long-term safety and efficacy of treatments in a real-world setting.The objective of the Corrona Psoriasis Registry is to study the comparative safety and efficacy of Food and Drug Administration–approved biologic treatments.A cross-sectional study of patients enrolled in the registry, who initiated or switched to a systemic therapy at enrollment or previous 12 months. Descriptive characteristics (demographics, clinical and patient-reported outcomes, comorbidities, and treatment history) were examined at registry enrollment.As of October 1, 2016, there were 1942 patients enrolled in the registry: 23% on apremilast, 4% on other nonbiologic systemic medications, 25% on interleukin (IL) 17A inhibitors, 22% on an IL-12/23 inhibitor, and 26% on tumor necrosis factor inhibitors. Overall, mean disease duration was 15.6 years, and 40% had a concurrent psoriatic arthritis diagnosis. About 66% had >3% body surface area involvement and 49% had a moderate or severe Investigator Global Assessment.Selection and channeling bias can result in potential confounding that needs to be addressed in modeled analyses.This disease-based registry cohort represents a population exposed to multiple therapies, long disease duration, and multiple comorbidities and can be used to examine comparative safety and efficacy of various therapies.