生物制剂治疗化脓性汗腺炎患者的药物生存情况。

Drug Survival of Biologics in Patients With Hidradenitis Suppurativa.

机构信息

Department of Dermato-Venereology & Wound Healing Centre, Bispebjerg Hospital, Copenhagen, Denmark.

Department of Dermatology, University of Zürich, Zürich, Switzerland.

出版信息

JAMA Dermatol. 2022 Feb 1;158(2):184-188. doi: 10.1001/jamadermatol.2021.4805.

Abstract

IMPORTANCE

Biologics are important in treating patients with hidradenitis suppurativa (HS). However, to our knowledge, data on their real-life performance and treatment patterns in HS are limited.

OBJECTIVE

To examine the drug survival of biologic therapies for HS in a real-world setting.

DESIGN, SETTING, AND PARTICIPANTS: This cohort study included all patients with HS between January 1, 2005, and December 31, 2018, who were treated with biologics at the 5 academic hospital clinics where all biologic treatment for HS is conducted in Denmark. Biologics included adalimumab, anakinra, certolizumab pegol, etanercept, golimumab, infliximab, secukinumab, and ustekinumab. Data were analyzed between June 1, 2021, and June 20, 2021.

MAIN OUTCOMES AND MEASURES

Drug survival was depicted through Kaplan-Meier curves, and Cox regression models were used to calculate adjusted (age, sex, previous number of biologic treatment series) hazard ratios (aHRs) with 95% CIs for the risk of treatment discontinuation. Switching patterns were visualized through a Sankey diagram.

RESULTS

The study comprised 241 patients (176 women [61.8%]; total of 386 treatment series) with a mean (SD) age of 41.8 (12.6) years at initiation of first biologic therapy. There were a total of 256 (189 [73.8%] biologic naive), 66 (32 [48.5%] biologic naive), 23 (9 [39.1%] biologic naive), and 22 (9 [40.9%] biologic naive) treatment series with adalimumab, infliximab, etanercept, and ustekinumab, respectively. The median time to discontinuation was 36.0 (IQR, 21.9-63.0), 28.7 (IQR, 15.1-62.9), 26.0 (IQR, 16.9-155.9), and 17.9 weeks (IQR, 12.9-41.0) for adalimumab, infliximab, ustekinumab and etanercept, respectively. The risk of drug discontinuation was significantly higher for etanercept compared with adalimumab (aHR, 1.81; 95% CI, 1.16-2.82), infliximab (aHR, 1.77; 95% CI, 1.03-3.05), and ustekinumab (aHR, 2.49; 95% CI, 1.12-5.52), whereas no difference was observed when comparing these 3 therapies with each other. We found no significant differences in drug survival for biologic-naive vs nonnaive treatment series. Increasing C-reactive protein levels (aHR, 1.01; 95% CI, 1.00-1.03) and concomitant antibiotic treatment (aHR, 2.82; 95% CI, 1.36-5.86) were associated with the risk of discontinuing infliximab therapy. Men (aHR, 0.69; 95% CI, 0.51-0.91) had a reduced risk of discontinuing use of adalimumab.

CONCLUSIONS AND RELEVANCE

In this cohort study, drug survival was comparable between adalimumab, infliximab, and ustekinumab but significantly lower for etanercept. There were no differences in drug survival among biologic-naive and nonnaive patients.

摘要

重要性:生物制剂在治疗化脓性汗腺炎(HS)患者方面具有重要作用。然而,据我们所知,关于其在 HS 中的实际表现和治疗模式的数据非常有限。

目的:在真实环境中检查生物疗法治疗 HS 的药物存活率。

设计、地点和参与者:本队列研究包括 2005 年 1 月 1 日至 2018 年 12 月 31 日期间在丹麦 5 家学术医院诊所接受生物治疗的所有 HS 患者。生物制剂包括阿达木单抗、阿那白滞素、 Certolizumab pegol、依那西普、戈利木单抗、英夫利昔单抗、司库奇尤单抗和乌司奴单抗。数据分析于 2021 年 6 月 1 日至 2021 年 6 月 20 日进行。

主要结果和措施:通过 Kaplan-Meier 曲线描绘药物存活率,并使用 Cox 回归模型计算调整后的(年龄、性别、之前的生物治疗系列数量)风险比(aHR),用于治疗中断的风险。通过 Sankey 图可视化转换模式。

结果:该研究纳入了 241 名患者(176 名女性[61.8%];首次接受生物治疗时的平均[SD]年龄为 41.8[12.6]岁)。共有 256 个(189 个[73.8%]生物治疗初治)、66 个(32 个[48.5%]生物治疗初治)、23 个(9 个[39.1%]生物治疗初治)和 22 个(9 个[40.9%]生物治疗初治)阿达木单抗、英夫利昔单抗、依那西普和乌司奴单抗治疗系列。阿达木单抗、英夫利昔单抗、乌司奴单抗和依那西普的停药中位时间分别为 36.0(IQR,21.9-63.0)、28.7(IQR,15.1-62.9)、26.0(IQR,16.9-155.9)和 17.9 周(IQR,12.9-41.0)。与阿达木单抗相比,依那西普(aHR,1.81;95%CI,1.16-2.82)、英夫利昔单抗(aHR,1.77;95%CI,1.03-3.05)和乌司奴单抗(aHR,2.49;95%CI,1.12-5.52)停药的风险显著更高,而这 3 种治疗方法之间比较无差异。我们发现生物治疗初治和非初治治疗系列之间的药物存活率没有显著差异。C 反应蛋白水平升高(aHR,1.01;95%CI,1.00-1.03)和同时使用抗生素治疗(aHR,2.82;95%CI,1.36-5.86)与英夫利昔单抗治疗停药的风险相关。男性(aHR,0.69;95%CI,0.51-0.91)使用阿达木单抗的停药风险降低。

结论和相关性:在这项队列研究中,阿达木单抗、英夫利昔单抗和乌司奴单抗的药物存活率相当,但依那西普的药物存活率显著降低。生物治疗初治和非初治患者的药物存活率无差异。

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