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接受布罗达umab 治疗的银屑病患者的循环布罗达umab 水平与治疗结果:病例系列研究。

Circulating Brodalumab Levels and Therapy Outcomes in Patients With Psoriasis Treated With Brodalumab: A Case Series.

机构信息

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.

出版信息

JAMA Dermatol. 2022 Jul 1;158(7):762-769. doi: 10.1001/jamadermatol.2022.1863.

Abstract

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.

摘要

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。

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