Department of Medicine, University of Ottawa, Ottawa, Canada; The Ottawa Hospital Research Institute, Ottawa, Canada.
Center for Administrative Data Research, Institute for Informatics, Washington University in St. Louis School of Medicine, St. Louis, Missouri.
Clin Gastroenterol Hepatol. 2024 Feb;22(2):377-385.e5. doi: 10.1016/j.cgh.2023.08.017. Epub 2023 Sep 4.
BACKGROUND & AIMS: Comparative effectiveness of biologics in preventing penetrating disease (PD) in Crohn's disease (CD) is not well established. We compared the risk of developing luminal and perianal PD (LPD and PPD) between biologics used as first-line therapies.
Adults (>17 years) with CD who initiated their first biologic (anti-tumor necrosis factor [anti-TNF], ustekinumab [UST], or vedolizumab [VDZ]) were identified from Merative Commercial Database (2006 and 2020). We excluded preexisting PD using a minimum look-back period of 1 year. Cohorts were balanced by inverse probability of treatment weighting based on age, sex, comorbidities, prior CD surgery, and CD severity. Pairwise comparisons were performed by Cox proportional hazards models, adjusted for immunomodulator exposure, and with biologic exposure treated as a time-dependent variable based on a medication possession ratio of 0.8.
Our analysis included 40,693 patients: 93% anti-TNF, 3% UST, and 4% VDZ. After inverse probability of treatment weighting all comparisons were well balanced. Anti-TNF was protective against LPD (hazard ratio, 0.66; 95% confidence interval, 0.55-0.78; P < .0001) and PPD (hazard ratio, 0.88; 95% confidence interval, 0.80-0.96; P = .0045) compared with VDZ and LPD (hazard ratio, 0.37; 95% confidence interval, 0.30-0.46; P < .0001) compared with UST. There were no significant differences in the risk of LPD and PPD between VDZ and UST. These results were similar after limiting the study period to after 2016.
Anti-TNF therapy was associated with a lower risk of LPD and PPD compared with VDZ, and lower risk of LPD compared with UST. Further studies are needed to validate these findings and to determine potential reasons for these differences.
生物制剂在预防克罗恩病（CD）穿透性疾病（PD）方面的疗效比较尚不清楚。我们比较了作为一线治疗药物的生物制剂在发生肠内和肛周 PD（LPD 和 PPD）方面的风险。
从 Merative Commercial Database（2006 年和 2020 年）中确定了首次接受生物制剂（抗肿瘤坏死因子[anti-TNF]、ustekinumab [UST]或 vedolizumab [VDZ]）治疗的>17 岁 CD 成人患者。使用至少 1 年的回顾期排除预先存在的 PD。通过基于年龄、性别、合并症、既往 CD 手术和 CD 严重程度的逆概率治疗加权法对队列进行平衡。使用 Cox 比例风险模型进行两两比较，调整免疫调节剂暴露情况，并根据药物维持率 0.8 将生物制剂暴露作为时间依赖性变量进行处理。
我们的分析纳入了 40693 名患者：93%接受 anti-TNF 治疗，3%接受 UST 治疗，4%接受 VDZ 治疗。经过逆概率治疗加权后，所有比较均达到良好的平衡。与 VDZ 相比，anti-TNF 可预防 LPD（风险比，0.66；95%置信区间，0.55-0.78；P<.0001）和 PPD（风险比，0.88；95%置信区间，0.80-0.96；P=0.0045）；与 UST 相比，anti-TNF 可预防 LPD（风险比，0.37；95%置信区间，0.30-0.46；P<.0001）。VDZ 与 UST 相比，LPD 和 PPD 的风险无显著差异。在将研究期限限制在 2016 年后，这些结果仍然相似。
与 VDZ 相比，anti-TNF 治疗与较低的 LPD 和 PPD 风险相关，与 UST 相比，LPD 风险也较低。需要进一步研究来验证这些发现，并确定这些差异的潜在原因。
