We report long-term, end-of-study program safety outcomes from 25 randomized clinical trials (RCTs) in adult patients with psoriasis (PsO), psoriatic arthritis (PsA), or axial spondyloarthritis (axSpA) [including ankylosing spondylitis (AS) and non-radiographic axial spondyloarthritis (nr-axSpA)] who received ≥ 1 dose of Ixekizumab (IXE) over 5 years (PsO) or up to 3 years (PsA, axSpA). This integrated safety analysis consists of data from patients who received any dose of IXE, across 25 RCTs (17 PsO, 4 PsA, 4 axSpA). Rates of treatment-emergent adverse events (TEAEs), serious adverse events (SAEs) and selected adverse events (AEs) of interest were analyzed for all pooled studies by years of therapy and overall, through March 2022. Results were reported as exposure-adjusted incidence rates (IRs) per 100 patient-years (PY) overall and at successive year intervals. Six thousand eight hundred ninety two adult patients with PsO, 1401 with PsA, and 932 with axSpA (including AS and nr-axSpA), with a cumulative IXE exposure of 22,371.1 PY were included. The most commonly reported TEAE across indications was nasopharyngitis (IRs per 100 PY: 8.8 (PsO), 9.0 (PsA), 8.4 (axSpA)). SAEs were reported by 969 patients with PsO (IR 5.4), 134 patients with PsA (IR 6.0), and 101 patients with axSpA (IR 4.8). Forty-five deaths were reported (PsO, n = 36, IR 0.2; PsA, n = 6, IR 0.3; axSpA, n = 3, IR 0.1). TEAEs did not increase during IXE exposure: IRs per 100 PY, PsO: 88.9 to 63.2 (year 0–1 to 4–5), PsA: 87 to 67.3 (year 0–1 to 2–3), axSpA: 82.1 to 55.4 (year 0–1 to > = 2). IRs per 100 PY of discontinuation from IXE due to AE were 2.9 (PsO), 5.1 (PsA), and 3.1 (axSpA). IRs per 100 PY of injection site reactions were 5.9 (PsO), 11.6 (PsA) and 7.4 (axSpA); Candida: 1.9 (PsO), 2.0 (PsA), and 1.2 (axSpA); depression, major adverse cerebro-cardiovascular events and malignancies: ≤ 1.6 across all indications. Adjudicated IRs per 100 PY of inflammatory bowel disease were ≤ 0.8 across indications (0.1 [PsO]; 0.1 [PsA]; 0.8 [axSpA]). In this integrated safety analysis, consisting of over 22,000 PY of exposure, the long-term safety profile of IXE was found to be consistent with previous, earlier reports, with no new safety signals identified. NCT registration numbers for RCTs included in this integrated analysis can be found in Additional File 1.

中文翻译：

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Ixekizumab 在成人银屑病、银屑病关节炎或中轴型脊柱关节炎患者中的长期安全性：对 25 项随机临床试验的最终安全性数据进行事后分析

我们报告了针对银屑病 (PsO)、银屑病关节炎 (PsA) 或中轴型脊柱关节炎 (axSpA) [包括强直性脊柱炎 (AS)] 成年患者的 25 项随机临床试验 (RCT) 的长期研究结束项目安全性结果和非放射学中轴​​脊柱关节炎（nr-axSpA）]在5年（PsO）或长达3年（PsA，axSpA）内接受≥1剂量的Ixekizumab（IXE）。该综合安全性分析包含来自接受任何剂量 IXE 的患者的数据，涉及 25 项随机对照试验（17 项 PsO、4 项 PsA、4 项 axSpA）。截至 2022 年 3 月，所有汇总研究均按治疗年数和总体情况分析了治疗中出现的不良事件 (TEAE)、严重不良事件 (SAE) 和选定的感兴趣的不良事件 (AE) 的发生率。结果按暴露调整后报告总体和连续年份间隔每 100 患者年 (PY) 的发病率 (IR)。纳入了 6892 名 PsO 成年患者、1401 名 PsA 患者和 932 名 axSpA 患者（包括 AS 和 nr-axSpA），累积 IXE 暴露量为 22,371.1 PY。最常报告的跨适应症 TEAE 是鼻咽炎（每 100 PY 的 IR：8.8 (PsO)、9.0 (PsA)、8.4 (axSpA)）。 969 名 PsO 患者（IR 5.4）、134 名 PsA 患者（IR 6.0）和 101 名 axSpA 患者（IR 4.8）报告了 SAE。报告了 45 例死亡（PsO，n = 36，IR 0.2；PsA，n = 6，IR 0.3；axSpA，n = 3，IR 0.1）。 IXE 暴露期间 TEAE 没有增加：每 100 PY 的 IR、PsO：88.9 至 63.2（第 0-1 年至 4-5 年）、PsA：87 至 67.3（第 0-1 年至 2-3 年）、axSpA：82.1 至 55.4 （0–1 年到 > = 2 年）。因 AE 停药的每 100 PY 的 IR 分别为 2.9 (PsO)、5.1 (PsA) 和 3.1 (axSpA)。每 100 PY 注射部位反应的 IR 分别为 5.9 (PsO)、11.6 (PsA) 和 7.4 (axSpA)；念珠菌：1.9 (PsO)、2.0 (PsA) 和 1.2 (axSpA)；抑郁症、主要不良脑心血管事件和恶性肿瘤：所有适应症≤1.6。各适应症中每 100 PY 炎症性肠病的判定 IR ≤ 0.8（0.1 [PsO]；0.1 [PsA]；0.8 [axSpA]）。在这项由超过 22,000 PY 的暴露组成的综合安全分析中，发现 IXE 的长期安全状况与之前的早期报告一致，没有发现新的安全信号。此综合分析中包含的 RCT 的 NCT 注册号可在附加文件 1 中找到。