Ixekizumab和恶性肿瘤：来自25个随机临床试验数据的汇总分析。

IF 11 1区医学 Q1 DERMATOLOGY

JAMA dermatology Pub Date : 2025-07-09 DOI:10.1001/jamadermatol.2025.2056

Joseph F Merola, Kim A Papp, Atul Deodhar, Andrew Blauvelt, Andris Kronbergs, Meghan Feely McDonald, Nadezdha Eberhart, Danting Zhu, Elsa Inman, Elsie Grace, Thorsten Holzkaemper, Proton Rahman, Helena Marzo-Ortega, Alice B Gottlieb, Sergio Schwartzman, Mark Lebwohl

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引用次数: 0

摘要

重要性：评估长期生物暴露患者的恶性肿瘤风险是有意义的。这项研究提供了银屑病（PsO）、银屑病关节炎（PsA）或轴性脊柱炎（axSpA）患者接受ixekizumab （IXE）治疗后恶性肿瘤风险的见解。目的：确定接受长期（长达6年）IXE治疗的PsO、PsA或axSpA患者的恶性肿瘤发生率，并将记录的发病率（不包括非黑色素瘤皮肤癌）与美国普通人群中观察到的发病率进行比较。设计、环境和参与者：这项多中心、全球汇总分析检查了来自25项随机临床试验（rct）的患者数据，这些患者患有PsO、PsA或axSpA，在5年（PsO）或3年（PsA和axSpA）期间接受至少1剂IXE治疗。入选标准在25项随机对照试验中各不相同，但大多数患者是初次接受生物治疗。初步分析于2021年3月（PsA）和2022年3月（PsO和axSpA）进行。干预措施：长期IXE治疗。主要结局和指标：恶性肿瘤发生率和标准化发病率比（SIRs）。结果：3种适应症患者的平均年龄为45.9岁；PsO和axSpA队列中的大多数患者为男性（分别为4696/6892[68.1%]和650/932[69.7%]），而PsA队列中的男女比例基本平衡（分别为679/1401[48.5%]和722/1401[51.5%]）。该研究包括6892名PsO患者，1401名PsA患者和932名axSpA患者，代表IXE的累积暴露量为22 371.1患者年（18 025.7 PY为PsO， 2247.7 PY为PsA， 2097.7 PY为axSpA）。141例PsO患者中有恶性肿瘤报告(2.0%；发病率[IR]， 0.8 / 100 PY [95% CI, 0.7-0.9])， PsA 15例(1.1%；IR, 0.7 / 100 PY [95% CI, 0.4-1.1])， 9例axSpA患者(1.0%；IR为0.4 / 100 PY [95% CI, 0.2-0.8])。恶性肿瘤的ir在1年的间隔仍然很低（≤1.2 / 100 PY），并且随着时间的推移保持不变。95% CI的SIRs低于或接近1 (PsO, 0.89 [95% CI, 0.71-1.08]；PsA, 0.49 [95% CI, 0.13-0.85]；axSpA, 1.07 [95% CI, 0.37-1.77])。结论和相关性：对25项随机对照试验的汇总分析表明，IXE的安全性支持PsO、PsA或axSpA患者的长期使用。恶性肿瘤的发病率与以前的报道一致，恶性肿瘤的SIRs与美国一般人群的适应症相似，证明了这一点。

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Ixekizumab and Malignant Neoplasms: A Pooled Analysis of Data From 25 Randomized Clinical Trials.

Importance: Assessing malignant neoplasm risk among patients with long-term biologic exposure is of interest. This study provides insight into the risk of malignant neoplasm among patients with psoriasis (PsO), psoriatic arthritis (PsA), or axial spondyloarthritis (axSpA) who received ixekizumab (IXE) over time.

Objective: To determine the incidence of malignant neoplasms among patients with PsO, PsA, or axSpA who received long-term (up to 6 years) IXE treatment, and to compare the recorded incidences (excluding nonmelanoma skin cancer) with those observed in the US general population.

Design, setting, and participants: This multicenter, global pooled analysis examined patient data from 25 randomized clinical trials (RCTs) in patients with PsO, PsA, or axSpA receiving at least 1 dose of IXE over 5 years (PsO) or 3 years (PsA and axSpA). Eligibility criteria varied across the 25 RCTs, but most of the patients were naive to biologic treatments. The primary analysis was performed in March 2021 (PsA) and March 2022 (PsO and axSpA).

Intervention: Long-term treatment with IXE.

Main outcomes and measures: Incidence rates of malignant neoplasms and standardized incidence ratios (SIRs).

Results: The mean age across the 3 indications was 45.9 years; most patients in the PsO and axSpA cohorts were male (4696/6892 [68.1%] and 650/932 [69.7%], respectively), whereas the proportion of male to female patients in the PsA cohort was largely balanced (679/1401 [48.5%] vs 722/1401 [51.5%], respectively). The study included 6892 patients with PsO, 1401 patients with PsA, and 932 patients with axSpA, representing a cumulative exposure to IXE of 22 371.1 patient-years (PY) (18 025.7 PY for PsO, 2247.7 PY for PsA, and 2097.7 PY for axSpA). Malignant neoplasms were reported among 141 patients with PsO (2.0%; incidence rate [IR], 0.8 per 100 PY [95% CI, 0.7-0.9]), 15 patients with PsA (1.1%; IR, 0.7 per 100 PY [95% CI, 0.4-1.1]), and 9 patients with axSpA (1.0%; IR, 0.4 per 100 PY [95% CI, 0.2-0.8]). IRs of malignant neoplasms at 1-year intervals remained low (≤1.2 per 100 PY) and constant over time. SIRs with 95% CIs were below or near 1 (PsO, 0.89 [95% CI, 0.71-1.08]; PsA, 0.49 [95% CI, 0.13-0.85]; axSpA, 1.07 [95% CI, 0.37-1.77]).

Conclusions and relevance: This pooled analysis of 25 RCTs demonstrated that the safety profile of IXE supports long-term use in patients with PsO, PsA, or axSpA. This is evidenced by incidences of malignant neoplasms consistent with previous reports, and with SIRs of malignant neoplasms across indications similar to the US general population.

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来源期刊

JAMA dermatology DERMATOLOGY-

CiteScore

14.10

自引率

5.50%

发文量

300

期刊介绍： JAMA Dermatology is an international peer-reviewed journal that has been in continuous publication since 1882. It began publication by the American Medical Association in 1920 as Archives of Dermatology and Syphilology. The journal publishes material that helps in the development and testing of the effectiveness of diagnosis and treatment in medical and surgical dermatology, pediatric and geriatric dermatology, and oncologic and aesthetic dermatologic surgery. JAMA Dermatology is a member of the JAMA Network, a consortium of peer-reviewed, general medical and specialty publications. It is published online weekly, every Wednesday, and in 12 print/online issues a year. The mission of the journal is to elevate the art and science of health and diseases of skin, hair, nails, and mucous membranes, and their treatment, with the aim of enabling dermatologists to deliver evidence-based, high-value medical and surgical dermatologic care. The journal publishes a broad range of innovative studies and trials that shift research and clinical practice paradigms, expand the understanding of the burden of dermatologic diseases and key outcomes, improve the practice of dermatology, and ensure equitable care to all patients. It also features research and opinion examining ethical, moral, socioeconomic, educational, and political issues relevant to dermatologists, aiming to enable ongoing improvement to the workforce, scope of practice, and the training of future dermatologists. JAMA Dermatology aims to be a leader in developing initiatives to improve diversity, equity, and inclusion within the specialty and within dermatology medical publishing.