Division of Arthritis & Rheumatic Diseases (OP-09), Oregon Health & Science University, 3181 SW Sam Jackson Park Road, Portland, OR, 97239-3098, USA.
Swedish Medical Center and University of Washington, Seattle, USA.
Arthritis Res Ther. 2019 May 2;21(1):111. doi: 10.1186/s13075-019-1882-2.
Secukinumab, a fully human immunoglobulin G1-kappa monoclonal antibody that directly inhibits interleukin (IL)-17A, has been shown to have robust efficacy in the treatment of moderate-to-severe psoriasis (PsO), psoriatic arthritis (PsA), and ankylosing spondylitis (AS) demonstrating a rapid onset of action and sustained long-term clinical responses with a consistently favorable safety profile in multiple Phase 2 and 3 trials. Here, we report longer-term pooled safety and tolerability data for secukinumab across three indications (up to 5 years of treatment in PsO and PsA; up to 4 years in AS).
The integrated clinical trial safety dataset included data pooled from 21 randomized controlled clinical trials of secukinumab 300 or 150 or 75 mg in PsO (14 Phase 3 trials and 1 Phase 4 trial), PsA (3 Phase 3 trials), and AS (3 Phase 3 trials), along with post-marketing safety surveillance data with a cut-off date of June 25, 2017. Adverse events (AEs) were reported as exposure-adjusted incident rates (EAIRs) per 100 patient-years. Analyses included all patients who received ≥ 1 dose of secukinumab.
A total of 5181, 1380, and 794 patients from PsO, PsA, and AS clinical trials representing secukinumab exposures of 10,416.9, 3866.9, and 1943.1 patient-years, respectively, and post-marketing data from patients with a cumulative exposure to secukinumab of ~ 96,054 patient-years were included in the analysis. The most frequent AE was upper respiratory tract infection. EAIRs across PsO, PsA, and AS indications were generally low for serious infections (1.4, 1.9, and 1.2, respectively), Candida infections (2.2, 1.5, and 0.7, respectively), inflammatory bowel disease (0.01, 0.05, and 0.1, respectively), and major adverse cardiac events (0.3, 0.4, and 0.6, respectively). No cases of tuberculosis reactivation were reported. The incidence of treatment-emergent anti-drug antibodies was low with secukinumab across all studies, with no discernible loss of efficacy, unexpected alterations in pharmacokinetics, or association with immunogenicity-related AEs.
Secukinumab demonstrated a favorable safety profile over long-term treatment in patients with PsO, PsA, and AS. This comprehensive assessment demonstrated that the safety profile of secukinumab was consistent with previous reports in patients with PsO, PsA, and AS, supporting its long-term use in these chronic conditions.
司库奇尤单抗是一种完全人源化 IgG1-κ 单克隆抗体，可直接抑制白细胞介素（IL）-17A，在治疗中重度银屑病（PsO）、银屑病关节炎（PsA）和强直性脊柱炎（AS）方面显示出强大的疗效，在多项 2 期和 3 期临床试验中表现出快速起效和持续的长期临床应答，且安全性始终良好。在此，我们报告了司库奇尤单抗在三个适应证中的长期安全性和耐受性汇总数据（在 PsO 和 PsA 中治疗最长 5 年；在 AS 中最长 4 年）。
综合临床试验安全性数据集包括来自司库奇尤单抗 300 或 150 或 75mg 治疗 PsO（14 项 3 期试验和 1 项 4 期试验）、PsA（3 项 3 期试验）和 AS（3 项 3 期试验）的 21 项随机对照临床试验的汇总数据，以及截至 2017 年 6 月 25 日的上市后安全性监测数据。不良事件（AE）按暴露调整发生率（EAIR）/100 患者年报告。分析纳入了接受至少 1 剂司库奇尤单抗治疗的所有患者。
共纳入来自 PsO、PsA 和 AS 临床试验的 5181、1380 和 794 例患者，司库奇尤单抗暴露分别为 10416.9、3866.9 和 1943.1 患者年，以及来自接受约 96054 患者年司库奇尤单抗累积暴露的患者的上市后数据。最常见的 AE 是上呼吸道感染。在 PsO、PsA 和 AS 适应证中，严重感染（分别为 1.4、1.9 和 1.2）、假丝酵母菌感染（分别为 2.2、1.5 和 0.7）、炎症性肠病（分别为 0.01、0.05 和 0.1）和主要不良心脏事件（分别为 0.3、0.4 和 0.6）的 EAIR 通常较低。未报告结核再激活病例。在所有研究中，司库奇尤单抗的治疗相关抗药物抗体发生率较低，且没有观察到疗效丧失、药代动力学意外改变或与免疫原性相关 AE 相关。
在患有 PsO、PsA 和 AS 的患者中，司库奇尤单抗的长期治疗显示出良好的安全性。这项全面评估表明，司库奇尤单抗的安全性与之前在 PsO、PsA 和 AS 患者中的报告一致，支持其在这些慢性疾病中的长期使用。
