Low uveitis rates in patients with axial spondyloarthritis treated with bimekizumab: pooled results from phase 2b/3 trials.

IF 3.5 3区医学 Q2 CHEMISTRY, MEDICINAL ACS Medicinal Chemistry Letters Pub Date : 2024-11-14 DOI:10.1136/ard-2024-225933

Matthew A Brown, Martin Rudwaleit, Floris A van Gaalen, Nigil Haroon, Lianne S Gensler, Carmen Fleurinck, Alexander Marten, Ute Massow, Natasha de Peyrecave, Thomas Vaux, Katy White, Atul Deodhar, Irene van der Horst-Bruinsma

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Abstract

Objectives: Acute anterior uveitis ('uveitis') is a common axial spondyloarthritis (axSpA) extramusculoskeletal manifestation. Interleukin (IL)-17 is implicated in its pathogenesis, however, there is conflicting evidence for IL-17A inhibition in uveitis management. We report pooled analyses of uveitis incidence in patients receiving bimekizumab (BKZ), a monoclonal IgG1 antibody that selectively inhibits IL-17F in addition to IL-17A, from phase 2b/3 trials.

Methods: Data were pooled for patients receiving BKZ 160 mg or placebo in the double-blind treatment period of the phase 3 BE MOBILE 1 (NCT03928704; non-radiographic axSpA) and BE MOBILE 2 (NCT03928743; radiographic axSpA) trials. Data were separately pooled for patients treated with at least one BKZ dose in the BE MOBILE trials and their ongoing open-label extension (OLE; NCT04436640), and the phase 2b BE AGILE trial (NCT02963506; radiographic axSpA) and its ongoing OLE (NCT03355573). Uveitis rates and exposure-adjusted incidence rates (EAIR)/100 patient-years (PYs) are reported.

Results: In the BE MOBILE 1 and 2 double-blind treatment period, 0.6% (2/349) of patients receiving BKZ experienced uveitis vs 4.6% (11/237) receiving placebo (nominal p=0.001; EAIR (95% CI): 1.8/100 PYs (0.2 to 6.7) vs 15.4/100 PYs (95% CI 7.7 to 27.5)). In patients with history of uveitis, EAIR was lower in patients receiving BKZ (6.2/100 PYs (95% CI 0.2 to 34.8); 1.9%) vs placebo (70.4/100 PYs (95% CI 32.2 to 133.7); 20.0%; nominal p=0.004). In the phase 2b/3 pool (N=848; BKZ exposure: 2034.4 PYs), EAIR remained low (1.2/100 PYs (95% CI 0.8 to 1.8)).

Conclusions: Bimekizumab, a dual-IL-17A/F inhibitor, may confer protective effects for uveitis in patients with axSpA.

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接受比美单抗治疗的轴性脊柱关节炎患者葡萄膜炎发生率较低：2b/3期试验的汇总结果。

目的：急性前葡萄膜炎（"葡萄膜炎"）是一种常见的轴性脊柱关节炎（axSpA）骨外表现。白细胞介素（IL）-17与葡萄膜炎的发病机制有关，但在葡萄膜炎治疗中抑制IL-17A的证据却相互矛盾。我们报告了对接受比美单抗（bimekizumab，BKZ）治疗的患者葡萄膜炎发病率的汇总分析，比美单抗是一种单克隆 IgG1 抗体，除 IL-17A 外还能选择性抑制 IL-17F：汇总在 BE MOBILE 1（NCT03928704；非放射学axSpA）和 BE MOBILE 2（NCT03928743；放射学axSpA）三期试验的双盲治疗期间接受 BKZ 160 毫克或安慰剂治疗的患者的数据。在 BE MOBILE 试验及其正在进行的开放标签扩展试验 (OLE；NCT04436640)、BE AGILE 2b 期试验（NCT02963506；放射学轴性SpA）及其正在进行的开放标签扩展试验 (NCT03355573)中接受过至少一种剂量 BKZ 治疗的患者的数据单独汇总。报告了葡萄膜炎发病率和暴露调整发病率（EAIR）/100 患者年（PYs）：在 BE MOBILE 1 和 2 双盲治疗期间，0.6%（2/349）接受 BKZ 治疗的患者出现葡萄膜炎，而 4.6%（11/237）接受安慰剂治疗的患者出现葡萄膜炎（名义 p=0.001；EAIR（95% CI）：1.8/100 患者年（0.2 至 6.7） vs 15.4/100 患者年（95% CI 7.7 至 27.5））。在有葡萄膜炎病史的患者中，BKZ（6.2/100PYs（95% CI 0.2至34.8）；1.9%）与安慰剂（70.4/100PYs（95% CI 32.2至133.7）；20.0%；名义P=0.004）的EAIR较低。在2b/3期研究中（N=848；BKZ暴露量：2034.4年），EAIR仍然很低（1.2/100年（95% CI 0.8至1.8））：Bimekizumab是一种IL-17A/F双重抑制剂，可对轴性SpA患者的葡萄膜炎起到保护作用。

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来源期刊

ACS Medicinal Chemistry Letters CHEMISTRY, MEDICINAL-

CiteScore

7.30

自引率

2.40%

发文量

328

审稿时长

1 months

期刊介绍： ACS Medicinal Chemistry Letters is interested in receiving manuscripts that discuss various aspects of medicinal chemistry. The journal will publish studies that pertain to a broad range of subject matter, including compound design and optimization, biological evaluation, drug delivery, imaging agents, and pharmacology of both small and large bioactive molecules. Specific areas include but are not limited to: Identification, synthesis, and optimization of lead biologically active molecules and drugs (small molecules and biologics) Biological characterization of new molecular entities in the context of drug discovery Computational, cheminformatics, and structural studies for the identification or SAR analysis of bioactive molecules, ligands and their targets, etc. Novel and improved methodologies, including radiation biochemistry, with broad application to medicinal chemistry Discovery technologies for biologically active molecules from both synthetic and natural (plant and other) sources Pharmacokinetic/pharmacodynamic studies that address mechanisms underlying drug disposition and response Pharmacogenetic and pharmacogenomic studies used to enhance drug design and the translation of medicinal chemistry into the clinic Mechanistic drug metabolism and regulation of metabolic enzyme gene expression Chemistry patents relevant to the medicinal chemistry field.