Patients with hidradenitis suppurativa have substantial unmet clinical needs and scarce therapeutic options. We aimed to assess the efficacy and safety of bimekizumab, a monoclonal IgG1 antibody that selectively inhibits interleukin (IL)-17F and IL-17A, in patients with moderate-to-severe hidradenitis suppurativa. BE HEARD I and II were two identically designed, 48-week randomised, double-blind, placebo-controlled, multicentre phase 3 trials. Patients aged 18 years or older with moderate-to-severe hidradenitis suppurativa were randomly assigned 2:2:2:1 using interactive response technology (stratified by worst Hurley Stage at baseline and baseline systemic antibiotic use) to receive subcutaneous bimekizumab 320 mg every 2 weeks; bimekizumab 320 mg every 2 weeks to week 16, then every 4 weeks to week 48; bimekizumab 320 mg every 4 weeks to week 48; or placebo to week 16, then bimekizumab 320 mg every 2 weeks. The primary outcome was an hidradenitis suppurativa clinical response of at least 50%, defined as a reduction in total abscess and inflammatory nodule count of at least 50% from baseline with no increase from baseline in abscess or draining tunnel count (HiSCR50) at week 16. Efficacy analyses included all randomly assigned study patients (intention-to-treat population). Safety analyses included all patients who received at least one full or partial dose of study treatment in the safety set, and of bimekizumab in the active-medication set. These trials are registered at , and , and both are completed. Patients for BE HEARD I were recruited from Feb 19, 2020, to Oct 27, 2021, and 505 patients were enrolled and randomly assigned. Patients for BE HEARD II were recruited from March 2, 2020, to July 28, 2021, and 509 patients were enrolled and randomly assigned. The primary outcome at week 16 was met in the group who received bimekizumab every 2 weeks using modified non-responder imputation; higher responder rates were observed with bimekizumab versus placebo in both trials: 138 (48%) of 289 patients versus 21 (29%) of 72 patients in BE HEARD I (odds ratio [OR] 2·23 [97·5% CI 1·16–4·31]; p=0·0060) and 151 (52%) of 291 patients versus 24 (32%) of 74 patients in BE HEARD II (2·29 [1·22–4·29]; p=0·0032). In BE HEARD II, HiSCR50 was also met in the group who were administered bimekizumab every 4 weeks (77 [54%] of 144 24 [32%] of 74 with placebo; 2·42 [1·22–4·80]; p=0·0038). Responses were maintained or increased to week 48. Serious treatment-emergent adverse events were reported in 40 (8%) patients in BE HEARD I and in 24 (5%) patients in BE HEARD II treated with bimekizumab over 48 weeks. The most frequently reported treatment-emergent adverse events to week 48 were hidradenitis in both trials, in addition to coronavirus infection and diarrhoea in BE HEARD I, and oral candidiasis and headache in BE HEARD II. One death was reported across the two trials, and was due to congestive heart failure in a patient with substantial cardiovascular history treated with bimekizumab every 2 weeks in BE HEARD I (considered unrelated to bimekizumab treatment by the investigator). No new safety signals were observed. Bimekizumab was well tolerated by patients with hidradenitis suppurativa and produced rapid and deep clinically meaningful responses that were maintained up to 48 weeks. Data from these two trials support the use of bimekizumab for the treatment of patients with moderate-to-severe hidradenitis suppurativa. UCB Pharma.

中文翻译：

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bimekizumab 对中重度化脓性汗腺炎患者的疗效和安全性（BE HEARD I 和 BE HEARD II）：两项为期 48 周、随机、双盲、安慰剂对照、多中心 3 期试验


化脓性汗腺炎患者有大量未满足的临床需求和稀缺的治疗选择。我们的目的是评估 Bimekizumab（一种单克隆 IgG1 抗体，选择性抑制白细胞介素 (IL)-17F 和 IL-17A）对中重度化脓性汗腺炎患者的疗效和安全性。 BE HEARD I 和 II 是两项设计相同、为期 48 周的随机、双盲、安慰剂对照、多中心 3 期试验。使用交互式反应技术（按基线最差 Hurley 阶段和基线全身抗生素使用情况分层）将 18 岁或以上患有中重度化脓性汗腺炎的患者按 2:2:2:1 随机分配，每 2 次皮下注射 bimekizumab 320 mg几周； bimekizumab 320 mg 每 2 周至第 16 周，然后每 4 周至第 48 周； bimekizumab 320 mg 每 4 周至第 48 周；或安慰剂至第 16 周，然后每 2 周服用 bimekizumab 320 mg。主要结局是化脓性汗腺炎临床反应至少 50%，定义为第 16 周脓肿和炎性结节总数较基线减少至少 50%，且脓肿或引流道计数 (HiSCR50) 较基线没有增加疗效分析包括所有随机分配的研究患者（意向治疗人群）。安全性分析包括在安全组中接受至少一剂完整或部分研究治疗的所有患者，以及在活性药物组中接受 bimekizumab 的所有患者。这些试验在 、 和 处注册，并且均已完成。 BE HEARD I 的患者招募时间为 2020 年 2 月 19 日至 2021 年 10 月 27 日，共 505 名患者入组并随机分配。 BE HEARD II的患者招募时间为2020年3月2日至2021年7月28日，共有509名患者入组并随机分配。 使用改良的无反应者插补法，每两周接受 bimekizumab 治疗的组在第 16 周达到了主要结局；在两项试验中，bimekizumab 与安慰剂相比，观察到更高的反应率：BE HEARD I 中 289 名患者中的 138 名患者 (48%) 与 72 名患者中的 21 名患者 (29%)（比值比 [OR] 2·23 [97·5% CI 1] ·16–4·31]；p=0·0060) 和 BE HEARD II 中 291 名患者中的 151 名 (52%) 与 74 名患者中的 24 名 (32%) (2·29 [1·22–4·29]； p=0·0032）。在 BE HEARD II 中，每 4 周给予 bimekizumab 的组也达到了 HiSCR50（安慰剂组 144 人中的 77 人 [54%] 74 人中的 24 人 [32%]；2·42 [1·22–4·80]； p=0·0038）。反应维持或增加至第 48 周。在接受 bimekizumab 治疗的 48 周内，BE HEARD I 中的 40 名患者 (8%) 和 BE HEARD II 中的 24 名患者 (5%) 报告了严重的治疗引起的不良事件。两项试验中，截至第 48 周最常报告的治疗引起的不良事件是汗腺炎，此外，BE HEARD I 中的冠状病毒感染和腹泻，以及 BE HEARD II 中的口腔念珠菌病和头痛。两项试验报告了 1 例死亡，死亡原因为一名具有丰富心血管病史的患者，在 BE HEARD I 中每两周接受 bimekizumab 治疗（研究者认为与 bimekizumab 治疗无关）。没有观察到新的安全信号。化脓性汗腺炎患者对 Bimekizumab 的耐受性良好，并产生快速、深入且具有临床意义的反应，且反应可持续长达 48 周。这两项试验的数据支持使用 bimekizumab 治疗中重度化脓性汗腺炎患者。 UCB 制药公司。