UCB Pharma, Slough, United Kingdom.
Department of Dermatology, Zealand University Hospital, Roskilde.
JAMA Dermatol. 2021 Nov 1;157(11):1279-1288. doi: 10.1001/jamadermatol.2021.2905.
Hidradenitis suppurativa (HS) is a chronic inflammatory disease with a high burden for patients and limited existing therapeutic options.
To evaluate the efficacy and safety of bimekizumab, a monoclonal IgG1 antibody that selectively inhibits interleukin 17A and 17F in individuals with moderate to severe HS.
DESIGN, SETTING, AND PARTICIPANTS: This phase 2, double-blind, placebo-controlled randomized clinical trial with an active reference arm was performed from September 22, 2017, to February 21, 2019. The study included a 2- to 4-week screening period, a 12-week treatment period, and a 20-week safety follow-up. Of 167 participants screened at multiple centers, 90 were enrolled. Eligible participants were 18 to 70 years of age with a diagnosis of moderate to severe HS 12 months or more before baseline.
Participants with HS were randomized 2:1:1 to receive bimekizumab (640 mg at week 0, 320 mg every 2 weeks), placebo, or reference arm adalimumab (160 mg at week 0, 80 mg at week 2, and 40 mg every week for weeks 4-10).
The prespecified primary efficacy variable was the proportion of participants with a 50% or greater reduction from baseline in the total abscess and inflammatory nodule count with no increase in abscess or draining fistula count (Hidradenitis Suppurativa Clinical Response [HiSCR] at week 12. Exploratory variables included proportion achieving a modified HiSCR with 75% reduction of HiSCR criteria (HiSCR75) or a modified HiSCR with 90% reduction of HiSCR criteria (HiSCR90), change in Patient's Global Assessment of Pain, and Dermatology Life Quality Index total scores.
Eighty-eight participants received at least 1 dose of study medication (61 [69%] female; median age, 36 years; range, 18-69 years). Seventy-three participants completed the study, including safety follow-up. Bimekizumab demonstrated a higher HiSCR rate vs placebo at week 12 (57.3% vs 26.1%; posterior probability of superiority equaled 0.998, calculated using bayesian analysis). Bimekizumab demonstrated greater clinical improvements compared with placebo. Improvements in the International Hidradenitis Suppurativa Severity Score (IHS4) were seen at week 12 with bimekizumab (mean [SD] IHS4, 16.0 [18.0]) compared with placebo (mean [SD] IHS4, 40.2 [32.6]). More bimekizumab-treated participants achieved positive results on stringent outcome measures compared with placebo. At week 12, 46% of bimekizumab-treated participants achieved HiSCR75 and 32% achieved HiSCR90, whereas 10% of placebo-treated participants achieved HiSCR75 and none achieved HiSCR90; in adalimumab-treated participants, 35% achieved HiSCR75 and 15% achieved HiSCR90. One participant withdrew because of adverse events. Serious adverse events occurred in 2 of 46 bimekizumab-treated participants (4%), 2 of 21 placebo-treated participants (10%), and 1 of 21 adalimumab-treated participants (5%).
In this phase 2 randomized clinical trial, bimekizumab demonstrated clinically meaningful improvements across all outcome measures, including stringent outcomes. Bimekizumab's safety profile was consistent with studies of other indications, supporting further evaluation in participants with HS.
ClinicalTrials.gov Identifier: NCT03248531.
重要性： 化脓性汗腺炎（HS）是一种慢性炎症性疾病，给患者带来了沉重的负担，而且现有的治疗选择有限。
目的：评估 bimekizumab 的疗效和安全性，bimekizumab 是一种单克隆 IgG1 抗体，选择性抑制白细胞介素 17A 和 17F，用于中重度化脓性汗腺炎患者。
设计、地点和参与者：这是一项在 2017 年 9 月 22 日至 2019 年 2 月 21 日进行的、有活性对照臂的、2 期、双盲、安慰剂对照随机临床试验。该研究包括 2-4 周的筛选期、12 周的治疗期和 20 周的安全性随访。在多个中心筛选的 167 名参与者中，有 90 名被纳入。符合条件的参与者年龄在 18 至 70 岁之间，在基线前 12 个月被诊断为中重度化脓性汗腺炎。
干预措施：患有化脓性汗腺炎的参与者被随机分为 2:1:1 组，分别接受 bimekizumab（第 0 周 640mg，每 2 周 320mg）、安慰剂或参考臂阿达木单抗（第 0 周 160mg，第 2 周 80mg，第 4-10 周每周 40mg）。
主要结果和措施：预设的主要疗效变量是从基线开始，总脓肿和炎性结节计数减少 50%或更多，且脓肿或引流瘘管计数无增加（第 12 周时的化脓性汗腺炎临床反应[HiSCR]）。探索性变量包括达到改良 HiSCR 75%（HiSCR75）或改良 HiSCR 90%（HiSCR90）的比例，疼痛的患者整体评估和皮肤病生活质量指数总分的变化。
结果：88 名参与者至少接受了 1 剂研究药物（61 名[69%]女性；中位年龄 36 岁；范围 18-69 岁）。73 名参与者完成了研究，包括安全性随访。与安慰剂相比，bimekizumab 显示出更高的 HiSCR 率，在第 12 周时为 57.3% vs 26.1%（使用贝叶斯分析计算，后验优势概率等于 0.998）。与安慰剂相比，bimekizumab 显示出更大的临床改善。第 12 周时，bimekizumab 组（平均[标准差] IHS4，16.0[18.0]）与安慰剂组（平均[标准差] IHS4，40.2[32.6]）相比，国际化脓性汗腺炎严重程度评分（IHS4）有改善。与安慰剂相比，更多接受 bimekizumab 治疗的参与者在严格的疗效指标上取得了阳性结果。第 12 周时，46%的 bimekizumab 治疗组达到 HiSCR75，32%达到 HiSCR90，而安慰剂组分别为 10%和 0%；阿达木单抗治疗组分别为 35%和 15%。一名参与者因不良事件退出。bimekizumab 治疗组有 2 名（4%）和安慰剂治疗组有 2 名（10%）参与者出现严重不良事件，阿达木单抗治疗组有 1 名（5%）参与者出现严重不良事件。
结论和相关性：在这项 2 期随机临床试验中，bimekizumab 在所有疗效指标上均显示出显著的改善，包括严格的指标。bimekizumab 的安全性与其他适应症的研究一致，支持进一步评估化脓性汗腺炎患者。
试验注册：ClinicalTrials.gov 标识符：NCT03248531。
