Background: Psoriasis is a chronic immune-mediated inflammatory skin condition that has a significant negative impact on the physical, emotional, and psychosocial well-being of those affected. Ixekizumab (IXE) has demonstrated an early and high-level treatment response in the real-world setting. This study aimed to assess the rapidity and long-term disease severity and quality of life (QOL) outcomes among IXE-treated plaque psoriasis patients. Method: A retrospective cohort study was conducted at a single US dermatology referral center. Medical charts were reviewed for adult psoriasis patients starting IXE (index date) between March 22, 2016, and February 28, 2018. Disease severity and QOL data were abstracted up to one-year pre-IXE initiation and up to 35 months post-IXE initiation. Static Physician Global Assessment (sPGA), Body Surface Area (BSA), and Dermatology Life Quality Index (DLQI) were summarized at 1-month post-index and at 3-month intervals. Logistic regressions were performed to evaluate the 1-month response in relation to long-term sPGA, BSA, DLQI outcomes. Subgroup analysis were conducted to compare outcomes among biologic naïve and biologic experienced patients.Results: A total of 153 patients (median age at index: 47.7 years; 65.4% male; 93.5% Caucasian) were included in the study. Majority of patients (69%; n=106) were biologic experienced prior to IXE initiation. In the total study cohort, at 1-month post-index 58.8% of patients achieved sPGA (0,1), 55.9% achieved DLQI (0,1), and 66.9% achieved BSA≤1%. Patients with sPGA (0,1) at 1-month post-index had greater odds of remaining sPGA (0,1) and BSA≤1% at 24-month (sPGA 0,1: OR=10.1; 95% CI: 2.1-47.9; BSA≤1%: OR=13.3; 95% CI: 2.2-80.2). Among patients who achieved sPGA (0,1) at 1-month post-index, the proportion of patients with sPGA (0,1), DLQI (0,1), and BSA≤1% remained largely the same for the 24-month follow-up. Among biologic experienced and naïve patients, more than half achieved sPGA (0,1), DLQI (0,1), and BSA≤1% at 1-month after IXE initiation. Conclusion: This real-word study demonstrated that majority of patients initiating IXE achieved sPGA (0, 1), DLQI (0, 1) and BSA ≤1% targets within the first month of treatment and were able to maintain treatment response for up to 24 months independent of prior biologic exposure.