Centre Hospitalier Universitaire, Instead of APHP: Assistance Publique - Hôpitaux de Paris Rennes, University Rennes, Rennes, France; INSERM, CIC1414, Institut Nutrition Metabolisms and Cancer, Rennes, France.
Centre Hospitalier Universitaire, Instead of APHP: Assistance Publique - Hôpitaux de Paris Rennes, University Rennes, Rennes, France.
Clin Gastroenterol Hepatol. 2020 Mar;18(3):628-636. doi: 10.1016/j.cgh.2019.05.027. Epub 2019 May 22.
BACKGROUND & AIMS: Few data are available on the effects of tumor necrosis factor (TNF) antagonist therapy for patients with internal fistulizing Crohn's disease (CD) and there is debate regarding the risk of abscess. We aimed to assess the long-term efficacy and safety of anti-TNF therapy for patients with internal fistulas.
We performed a retrospective study of data collected from the Groupe d'Etude Thérapeutique des Affections Inflammatoires Digestives trial, from January 1, 2000, through December 31, 2017. Our final analysis included 156 patients who began treatment with an anti-TNF agent for CD with internal fistula (83 men; median disease duration, 4.9 y). The primary end point was the onset of a major abdominal surgery. Secondary analysis included disappearance of the fistula tract during follow-up evaluation and safety. The Kaplan-Meier method was used for statistical analysis.
After a median follow-up period of 3.5 years, 68 patients (43.6%) underwent a major abdominal surgery. The cumulative probabilities for being surgery-free were 83%, 64%, and 51% at 1, 3, and 5 years, respectively. A concentration of C-reactive protein >18 mg/L, an albumin concentration <36 g/L, the presence of an abscess at the fistula diagnosis, and the presence of a stricture were associated independently with the need for surgery. The cumulative probabilities of fistula healing, based on imaging analyses, were 15.4%, 32.3%, and 43.9% at 1, 3, and 5 years, respectively. Thirty-two patients (20.5%) developed an intestinal abscess and 4 patients died from malignancies (3 intestinal adenocarcinomas). One patient died from septic shock 3 months after initiation of anti-TNF therapy.
In a retrospective analysis of data from a large clinical trial, we found that anti-TNF therapy delays or prevents surgery for almost half of patients with CD and luminal fistulas. However, anti-TNF therapy might increase the risk for sepsis-related death or gastrointestinal malignancies.
关于肿瘤坏死因子（TNF）拮抗剂治疗有肠内瘘管形成的克罗恩病（CD）患者的效果，相关数据很少，而且关于脓肿风险存在争议。我们旨在评估抗 TNF 治疗对有肠内瘘管的患者的长期疗效和安全性。
我们对 2000 年 1 月 1 日至 2017 年 12 月 31 日期间收集的炎症性肠病治疗研究组的数据进行了回顾性研究。我们的最终分析包括 156 名开始用抗 TNF 药物治疗有肠内瘘管（83 名男性；中位疾病持续时间 4.9 年）的 CD 患者。主要终点是主要腹部手术的发生。次要分析包括随访评估期间瘘管通道的消失和安全性。统计分析采用 Kaplan-Meier 法。
中位随访 3.5 年后，68 名患者（43.6%）进行了主要腹部手术。1、3、5 年时无手术的累积概率分别为 83%、64%和 51%。C 反应蛋白浓度>18 mg/L、白蛋白浓度<36 g/L、瘘管诊断时存在脓肿以及存在狭窄与手术需求独立相关。根据影像学分析，瘘管愈合的累积概率分别为 15.4%、32.3%和 43.9%，1、3、5 年时分别为 15.4%、32.3%和 43.9%。32 名患者（20.5%）发生肠脓肿，4 名患者死于恶性肿瘤（3 例肠腺癌）。1 名患者在开始抗 TNF 治疗后 3 个月死于感染性休克。
在一项大型临床试验数据的回顾性分析中，我们发现抗 TNF 治疗可使近一半有肠内瘘管的 CD 患者延迟或避免手术。然而，抗 TNF 治疗可能会增加与脓毒症相关的死亡或胃肠道恶性肿瘤的风险。
