Domènech Eugeni, Fortuny Joan, Martínez David, Tormos Anita, Huang Zhiping, Hill Deanna D, Weinstein Cindy, Esslinger Suzan, Krumme Alexis A, Otero-Lobato Marijo, Mines Daniel, Gisbert Javier P
Gastroenterology Department, Hospital Universitari Germans Trias i Pujol, Autonomous University of Barcelona, Barcelona, Spain.
Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEREHD), Madrid, Spain.
Pharmacoepidemiol Drug Saf. 2025 Aug;34(8):e70176. doi: 10.1002/pds.70176.
Golimumab (GLM), an anti-tumour necrosis factor alpha (anti-TNFα) agent, is indicated for moderate to severe ulcerative colitis (UC). This post-authorisation safety study evaluated the risk of colectomy due to intractable disease and advanced colonic neoplasia (high-grade dysplasia and/or colorectal cancer) under real-world conditions of GLM use.
This bidirectional cohort study using Spanish ENEIDA registry data (2013-2022) included adults with UC who initiated GLM, other anti-TNFα agents, or thiopurines (TPs). Crude risk analyses-and, when feasible, multivariable models-in cohort and nested case-control designs were performed. For colectomy, we evaluated exposure to GLM only, other anti-TNFα agents, and both (i.e., overlapping exposure). For ACN, we evaluated exposure to GLM, other anti-TNFα agents, and TPs.
Sixty-four colectomy cases and 10 ACN cases were identified among patients exposed to GLM (N = 474), other anti-TNFα agents (N = 1737), or TPs (N = 1380). Incidence rates per 1000 person-years and 95% confidence intervals were reported for colectomy (GLM-only [4.4, 1.2-11.2] and other anti-TNFα agents only [12.4, 9.1-16.5]) and ACN (GLM [1.5, 0.2-5.4], other anti-TNFα agents [1.3, 0.5-2.8], and TPs [1.0, 0.3-2.6]). In comparisons excluding overlapping exposure, GLM was not associated with an increased risk of colectomy versus other anti-TNFα agents. GLM was also not associated with an increased risk of ACN versus either comparator. Observed events, especially for ACN, were limited for all exposures.
Findings do not indicate an increased risk of colectomy due to intractable disease or ACN with GLM use versus other therapies for similar disease severity in routine UC care (EUPAS15752).
戈利木单抗（GLM）是一种抗肿瘤坏死因子α（抗TNFα）药物，适用于中度至重度溃疡性结肠炎（UC）。这项批准后安全性研究评估了在GLM实际使用情况下，因难治性疾病和晚期结肠肿瘤（高级别异型增生和/或结直肠癌）而进行结肠切除术的风险。
这项双向队列研究使用了西班牙ENEIDA登记数据（2013 - 2022年），纳入了开始使用GLM、其他抗TNFα药物或硫唑嘌呤（TPs）的成年UC患者。在队列和巢式病例对照设计中进行了粗风险分析，并在可行时进行多变量模型分析。对于结肠切除术，我们仅评估了GLM暴露、其他抗TNFα药物暴露以及两者（即重叠暴露）。对于高级别异型增生和结直肠癌（ACN），我们评估了GLM暴露、其他抗TNFα药物暴露以及TPs暴露。
在暴露于GLM（N = 474）以及其他抗TNFα药物（N = 1737）或TPs（N = 1380）的患者中，分别确定了64例结肠切除术病例和十例ACN病例。报告了每1000人年的发病率及95%置信区间，结肠切除术（仅GLM组[4.4，1.2 - 11.2]以及仅其他抗TNFα药物组[12.4，9.1 - 16.5]）以及ACN（GLM组[1.5，0.2 - 5.4]，其他抗TNFα药物组[1.3，0.5 - 2.8]，TPs组[1.0，0.3 - 2.6]）。在排除重叠暴露的比较中，与其他抗TNFα药物相比，GLM与结肠切除风险增加无关。与任何一种对照药物相比，GLM与ACN风险增加也无关。观察到的事件，尤其是ACN事件，在所有暴露组中都有限。
研究结果并未表明，在常规UC护理（EUPAS15752）中，与治疗类似疾病严重程度的其他疗法相比，使用GLM会因难治性疾病或ACN导致结肠切除风险增加。
