Plaque psoriasis is a chronic disease requiring long-term therapy. However, long-term real-world treatment patterns and costs are not well characterized. This study examined treatment patterns and healthcare costs among patients newly initiating a biologic or apremilast for moderate-to-severe plaque psoriasis. Included patients had ?1 prescription for secukinumab, ixekizumab, adalimumab, ustekinumab, etanercept, or apremilast between 01/01/2015 and 08/31/2018, no prior use of the index medication, and continuous enrolment 12 months pre-index and 24 months post-index. Treatment adherence, non-persistence, discontinuation, switching, use of combination therapy, and re-initiation were assessed at 12, 18, and 24 -months post-index. In addition, total and psoriasis-related healthcare costs were evaluated at 24 months. A total of 7,773 patients with 24-month follow-up were included. Overall, adherence was low (21.3%-33.5%) and non-persistence was high (58.4%-86.5%) over 24 months. Discontinuation (38.4%-51.3%), switching (29.7%-52.6%), combination therapy (27.6%-42.9%), and re-initiation of the index medication (19.3%-44.5%) were common. Healthcare costs were high and mostly contributed by psoriasis treatment. Therefore, maintaining disease control on long-term therapy is still challenging for many patients.