Inflammatory Bowel Disease Clinic, University of Calgary, Alberta, Canada; Division of Gastroenterology, University of Calgary, Alberta, Canada; Department of Medicine, University of Calgary, Alberta, Canada; Nottingham Digestive Diseases Centre, Biomedical Research Unit, University of Nottingham, Nottingham, United Kingdom.
Inflammatory Bowel Disease Clinic, University of Calgary, Alberta, Canada; Division of Gastroenterology, University of Calgary, Alberta, Canada; Department of Medicine, University of Calgary, Alberta, Canada.
Clin Gastroenterol Hepatol. 2014 Mar;12(3):434-42.e1. doi: 10.1016/j.cgh.2013.08.026. Epub 2013 Aug 24.
BACKGROUND & AIMS: There is conflicting evidence on the effects of thiopurines (azathioprine or mercaptopurine) and anti-tumor necrosis factor (TNF) therapies on rates of surgery among patients with Crohn's disease (CD). We aimed to identify factors that identify patients who are unlikely to respond to medical therapy and will therefore require surgery.
We performed a retrospective study using the Alberta Inflammatory Bowel Disease Consortium registry to identify 425 patients diagnosed with CD who received a prescription of a thiopurine and/or an anti-TNF agent from a referral center, from July 1, 1975, through September 13, 2012. We collected data on CD-related abdominal surgery after therapy and disease features when therapy was instituted. Cox proportional regression models were used to associate disease features with outcomes after adjusting for potential confounders. Risk estimates were presented as hazard rate ratios (HRRs) with 95% confidence intervals (CIs).
Among patients given thiopurines, stricturing disease (adjusted HR, 4.63; 95% CI, 2.00-10.71), ileal location (adjusted HR, 6.20; 95% CI, 1.64-23.42), and ileocolonic location (adjusted HR, 3.71; 95% CI, 1.08-12.74) at the time of prescription were associated significantly with the need for surgery. Prescription of an anti-TNF agent after prescription of a thiopurine reduced the risk for surgery, compared with patients prescribed only a thiopurine (adjusted HR, 0.41; 95% CI, 0.22-0.75). Among patients given anti-TNF agents, stricturing (adjusted HR, 6.17; 95% CI, 2.81-13.54) and penetrating disease (adjusted HR, 3.39; 95% CI, 1.45-7.92) at the time of prescription were associated significantly with surgery. Older age at diagnosis (17-40 y) reduced the risk for abdominal surgery (adjusted HR, 0.41; 95% CI, 0.21-0.80) compared with a younger age group (≤16 y). Surgery before drug prescription reduced the risk for further surgeries among patients who received thiopurines (adjusted HR, 0.33; 95% CI, 0.13-0.68) or anti-TNF agents (adjusted HR, 0.49; 95% CI, 0.25-0.96). Terminal ileal disease location was not associated with a stricturing phenotype.
Based on a retrospective database analysis, patients prescribed thiopurine or anti-TNF therapy when they have a complicated stage of CD are more likely to require surgery. Better patient outcomes are achieved by treating CD at early inflammation stages; delayed treatment increases rates of treatment failure.
在患有克罗恩病（CD）的患者中，硫唑嘌呤（硫嘌呤或巯基嘌呤）和抗肿瘤坏死因子（TNF）疗法对手术率的影响存在相互矛盾的证据。我们旨在确定可识别出不太可能对药物治疗有反应并因此需要手术的患者的因素。
我们使用艾伯塔省炎症性肠病联合会注册中心进行了一项回顾性研究，以确定 425 名从 1975 年 7 月 1 日至 2012 年 9 月 13 日从转诊中心接受硫嘌呤和/或抗 TNF 药物处方的患有 CD 的患者。我们收集了治疗后与 CD 相关的腹部手术数据以及治疗开始时的疾病特征。使用 Cox 比例风险回归模型，在调整潜在混杂因素后，将疾病特征与治疗后的结果相关联。风险估计以危险率比（HRR）和 95%置信区间（CI）表示。
在接受硫嘌呤治疗的患者中，处方时存在狭窄性疾病（调整后的 HR，4.63；95%CI，2.00-10.71）、回肠部位（调整后的 HR，6.20；95%CI，1.64-23.42）和回结肠部位（调整后的 HR，3.71；95%CI，1.08-12.74）与手术的需要显著相关。与仅接受硫嘌呤治疗的患者相比，在接受硫嘌呤治疗后处方抗 TNF 药物可降低手术风险（调整后的 HR，0.41；95%CI，0.22-0.75）。在接受抗 TNF 治疗的患者中，处方时存在狭窄性疾病（调整后的 HR，6.17；95%CI，2.81-13.54）和穿透性疾病（调整后的 HR，3.39；95%CI，1.45-7.92）与手术明显相关。与年龄较小的患者（≤16 岁）相比，诊断时年龄为 17-40 岁（调整后的 HR，0.41；95%CI，0.21-0.80）降低了腹部手术的风险。与药物治疗前接受手术的患者相比，接受硫嘌呤（调整后的 HR，0.33；95%CI，0.13-0.68）或抗 TNF 药物（调整后的 HR，0.49；95%CI，0.25-0.96）治疗的患者进一步手术的风险降低。末端回肠疾病部位与狭窄表型无关。
基于回顾性数据库分析，在患有 CD 的患者中处方硫嘌呤或抗 TNF 治疗时，他们更有可能需要手术。通过在炎症早期治疗 CD 可获得更好的患者结局；延迟治疗会增加治疗失败的风险。
