在中重度斑块型银屑病患者中，经过 2 年的比美吉珠单抗治疗的安全性和有效性：来自 BE SURE 随机对照试验和 BE BRIGHT 试验开放标签扩展的长期结果。

Safety and efficacy of bimekizumab through 2 years in patients with moderate-to-severe plaque psoriasis: longer-term results from the BE SURE randomized controlled trial and the open-label extension from the BE BRIGHT trial.

机构信息

Institute and Comprehensive Center for Inflammation Medicine, University Hospital of Lübeck, Lübeck, Germany.

Dermatrials Research Inc., Hamilton, ON, Canada.

出版信息

Br J Dermatol. 2023 Jan 23;188(1):22-31. doi: 10.1093/bjd/ljac021.

DOI:10.1093/bjd/ljac021

PMID:36689515

Abstract

BACKGROUND: BE SURE 1-year results demonstrated the superior efficacy of bimekizumab compared with adalimumab with no unexpected safety findings. OBJECTIVES: To provide efficacy and safety data over 2 years of bimekizumab treatment compared with adalimumab from BE SURE and the BE BRIGHT open-label extension (OLE) in patients with moderate-to-severe plaque psoriasis. METHODS: The 56-week double-blinded BE SURE phase III randomized controlled trial randomized patients 1 : 1 : 1 to bimekizumab 320 mg every 4 weeks (Q4W), bimekizumab 320 mg Q4W to week 16 then every 8 weeks (Q8W), or adalimumab 40 mg every 2 weeks to week 24 then bimekizumab 320 mg Q4W. After completing BE SURE, patients could enter the ongoing BE BRIGHT OLE, with possible dosing adjustments based on Psoriasis Area and Severity Index (PASI). The primary outcome in BE BRIGHT was incidence of treatment-emergent adverse events (TEAEs); safety data are reported by study period through week 104. Efficacy data are reported for the intention-to-treat population through week 104 by initial randomization group, with ≥ 90% improvement from baseline PASI (PASI 90) and 100% improvement (PASI 100) as key outcomes. RESULTS: Of the patients randomized to bimekizumab, 158 were assigned to Q4W, and 161 to Q4W/Q8W. At week 104, PASI 90 was achieved by 91.2% and 89.7%, and PASI 100 was achieved by 72.3% and 68.1%, for Q4W and Q4W/Q8W, respectively; comparable to week 16 results. Among the 159 patients randomized to adalimumab, responses rapidly and substantially increased after the week 24 bimekizumab switch; at week 104, 96.9% and 70.2% of patients achieved PASI 90 and PASI 100 respectively. Through weeks 24-104, the three most common TEAEs in any bimekizumab-treated group were nasopharyngitis, oral candidiasis and upper respiratory tract infection. Rates of serious TEAEs were low. CONCLUSIONS: Clinical responses observed through week 16 of BE SURE in patients randomized to bimekizumab were sustained through 104 weeks of treatment, regardless of Q4W or Q8W maintenance dosing. Response rates were also sustained through week 104 in patients who switched from adalimumab to bimekizumab at week 24, and were similar to those observed in the bimekizumab groups. Bimekizumab was well tolerated with no new safety signals.

摘要

背景：BE SURE 研究的 1 年结果表明，比美吉珠单抗的疗效优于阿达木单抗，且未发现新的安全性问题。

目的：提供比美吉珠单抗治疗 2 年的疗效和安全性数据，与 BE SURE 中的阿达木单抗以及 BE BRIGHT 开放标签扩展（OLE）进行比较，入组患者为中重度斑块状银屑病。

方法：在这项为期 56 周的双盲 BE SURE III 期随机对照试验中，患者按照 1:1:1 的比例随机分组，分别接受比美吉珠单抗 320mg 每 4 周（Q4W）、比美吉珠单抗 320mg Q4W 至第 16 周，然后每 8 周（Q8W）、或阿达木单抗 40mg 每 2 周至第 24 周，然后 Q4W 转换为比美吉珠单抗 320mg。完成 BE SURE 后，患者可进入正在进行的 BE BRIGHT OLE，可根据银屑病面积和严重程度指数（PASI）进行可能的剂量调整。BE BRIGHT 的主要终点是治疗出现的不良事件（TEAE）发生率；安全性数据按研究期报告至第 104 周。通过初始随机分组报告第 104 周时的疗效数据，关键结局为从基线 PASI 改善≥90%（PASI 90）和 100%（PASI 100）。

结果：接受比美吉珠单抗治疗的患者中，158 例被分配至 Q4W 组，161 例被分配至 Q4W/Q8W 组。在第 104 周时，Q4W 和 Q4W/Q8W 组的 PASI 90 分别为 91.2%和 89.7%，PASI 100 分别为 72.3%和 68.1%；与第 16 周的结果相当。在 159 例被分配至阿达木单抗的患者中，在第 24 周转换为比美吉珠单抗后，应答迅速且大幅增加；在第 104 周时，分别有 96.9%和 70.2%的患者达到 PASI 90 和 PASI 100。在第 24 周到第 104 周期间，任何接受比美吉珠单抗治疗的患者中最常见的三种治疗出现的不良事件是鼻咽炎、口腔念珠菌病和上呼吸道感染。严重治疗出现的不良事件发生率较低。

结论：在 BE SURE 中接受比美吉珠单抗治疗的患者在第 16 周观察到的临床应答在治疗的第 104 周持续存在，无论 Q4W 或 Q8W 维持剂量如何。在第 24 周转换为比美吉珠单抗的患者中，应答率也在第 104 周持续存在，与比美吉珠单抗组观察到的情况相似。比美吉珠单抗耐受性良好，无新的安全性信号。