Institute for Inflammation Research, Center for Rheumatology and Spine Diseases, Rigshospitalet, Copenhagen University Hospital, Copenhagen, Denmark.
Department of Dermatology and Allergy, Copenhagen University Hospital-Herlev and Gentofte, Copenhagen, Denmark.
JAMA Dermatol. 2022 Jul 1;158(7):762-769. doi: 10.1001/jamadermatol.2022.1863.
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.
重要性：鉴于在银屑病管理中可能存在的治疗方式，对于药物监测是否与反应率相关知之甚少。 目的：确定药物监测是否与 brodalumab 治疗的反应相关。 设计：一项多中心病例系列研究，纳入了在丹麦 Gentofte 和奥胡斯大学医院皮肤科接受 brodalumab 治疗且先前接受 IL-17A 抑制剂治疗失败的银屑病患者。研究于 2018 年至 2020 年期间招募患者。在治疗的第 4 周和第 12 周后进行患者访视。在 12 周后未达到从基线改善 75%的银屑病面积和严重程度指数（PASI 75）的患者被停药并被视为无应答者。维持 PASI 75 应答的患者随访长达 52 周。 暴露：在第 0、1、2 周和之后每 2 周接受 brodalumab，210mg。 主要结果和测量指标：结果测量指标为 PASI 减少量与 brodalumab 水平和抗 brodalumab 抗体。 结果：20 名银屑病患者（13 名[65%]为男性；中位年龄 50 岁[范围，19-66 岁]）纳入研究。在 12 周的治疗后，可检测到 brodalumab 水平（≥0.05μg/mL）的患者比未检测到的患者经历了显著更高的 PASI 减少量（中位数，93%；范围，61%-100%与中位数，-3；范围，-49%至 94%，分别；P = .006）。在 12 周的治疗后，4 名（80%）未达到 PASI 75 的患者的药物水平不可检测（<0.05μg/mL），尽管这一发现仅见于 14 名 PASI 75 应答者中的 3 名（21%）。在 12 周的治疗后，7 名（35%）不可检测药物水平的患者中，无一人维持应答。在任何检测样本中均未检测到抗 brodalumab 抗体。 结论和相关性：这项病例系列研究的结果表明，循环 brodalumab 水平是与临床治疗反应相关的因素。监测患者循环 brodalumab 水平可能有助于临床决策并有助于预防无效治疗。
N Engl J Med. 2015-10
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Acta Derm Venereol. 2023-11-21
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