Importance: Given the possible treatment modalities in psoriasis management, little is known about whether drug monitoring is associated with response rate. Objective: To determine whether drug monitoring is associated with response to brodalumab therapy. Design: A multicenter case series study of patients with psoriasis treated with brodalumab whose treatment with previous IL-17A inhibitor therapy failed. Patients were recruited from the Departments of Dermatology at Gentofte and Aarhus University Hospitals, Denmark, between 2018 and 2020. Patient visits were conducted after 4 and 12 weeks of therapy. Patients not achieving Psoriasis Area and Severity Index 75% improvement from baseline (PASI 75) after 12 weeks were discontinued and considered nonresponders. Patients maintaining PASI 75 response were followed up for up to 52 weeks. Exposure: Treatment with brodalumab, 210 mg, at weeks 0, 1, 2, then every 2 weeks. Main Outcomes and Measures: Outcome measures were PASI reductions vs brodalumab levels and antibrodalumab antibodies. Results: Twenty patients with psoriasis (13 [65%] were male; median age, 50 years [range, 19-66 years]) were included. After 12 weeks of therapy, patients with quantifiable levels of brodalumab (≥0.05 μg/mL) experienced significantly higher PASI reductions than those without (median, 93%; range, 61%-100% vs median,-3; range,-49% to 94%, respectively; P =.006). After 12 weeks of therapy, 4 of 5 patients (80%) not achieving PASI 75 had subquantifiable drug levels (<0.05 μg/mL), although this finding was seen for only 3 of 14 PASI 75 responders (21%). None of 7 patients (35%) with subquantifiable drug levels after 12 weeks of therapy maintained response. No antibrodalumab antibodies were detected in any of the tested samples. Conclusions and Relevance: Results of this case series study suggest that circulating brodalumab level is a factor associated with clinical treatment response. Monitoring patient levels of circulating brodalumab may aid clinical decision-making and help prevent ineffective therapy.