High body mass index is associated with increased risk of treatment failure and surgery in biologic-treated patients with ulcerative colitis
High body mass index is associated with increased risk of treatment failure and surgery in biologic-treated patients with ulcerative colitis
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DOI：
10.1111/apt.14665
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发表时间：
2018-06-01
影响因子：
7.6
通讯作者：
Singh, S.
中科院分区：
文献类型：
--
作者：
Kurnool, S.;Nguyen, N. H.;Singh, S.
背景：虽然药代动力学研究表明，随着体重的增加，生物药物清除速度加快，但肥胖对溃疡性结肠炎（UC）生物治疗患者临床结果影响的证据并不一致。目的：评估肥胖对UC患者对生物治疗的实际反应的影响。方法：在2011-2016年的单中心回顾性队列研究中，我们通过基线体重指数（BMI）评估治疗反应。主要结局是治疗失败（ibd相关手术/住院治疗或治疗调整的复合结局，包括剂量增加、停止治疗或添加皮质类固醇）；次要结局是ibd相关手术/住院的风险和内窥镜缓解。我们进行了多变量Cox比例风险分析来评估BMI对临床结果的独立影响。采用基于体重的方案（英夫利昔单抗）或固定剂量方案（阿达木单抗、戈利木单抗、维多利单抗、certolizumab pegol）进行分层分析。结果：我们纳入了160例生物治疗的UC患者（50%为男性，55%为英夫利昔单抗），中位（IQR）年龄为36岁（26-52岁），BMI为24.3 kg/m(2)（21.4-28.7）。在多变量分析中，BMI每增加1 kg/m(2)，治疗失败风险增加4%（校正风险比[aHR]， 1.04 [95% CI, 1.00-1.08]），手术/住院风险增加8% （aHR, 1.08[1.02-1.14]）。在以体重为基础的给药方案或固定剂量治疗方案的患者中可以看到对治疗失败的影响。结论：在生物治疗的UC患者中，BMI与治疗失败风险增加独立相关，与给药方案无关。
Background: Though pharmacokinetic studies suggest accelerated biologic drug clearance with increasing body weight, evidence of obesity's impact on clinical outcomes in biologic-treated patients with ulcerative colitis (UC) is inconsistent.Aim: To evaluate the impact of obesity on real world response to biological therapy in patients with UC.Methods: In a single-centre retrospective cohort study between 2011-2016 of biologic-treated patients with UC, we evaluated treatment response by baseline body mass index (BMI). Primary outcome was treatment failure (composite outcome of IBD-related surgery/hospitalisation or treatment modification including dose escalation, treatment discontinuation or addition of corticosteroids); secondary outcomes were risk of IBD-related surgery/hospitalisation and endoscopic remission. We conducted multivariate Cox proportional hazard analyses to evaluate the independent impact of BMI on clinical outcomes. Stratified analysis by weight-based regimens (infliximab) or fixed-dose regimens (adalimumab, golimumab, vedolizumab, certolizumab pegol) was performed.Results: We included 160 biologic-treated UC patients (50% males, 55% on infliximab) with median (IQR) age 36 y (26-52) and BMI 24.3 kg/m(2) (21.4-28.7). On multivariate analysis, each 1 kg/m(2) increase in BMI was associated with 4% increase in the risk of treatment failure (adjusted hazard ratio [aHR], 1.04 [95% CI, 1.00-1.08]) and 8% increase in the risk of surgery/hospitalisation (aHR, 1.08 [1.02-1.14]). The effect on treatment failure was seen in patients on weight-based dosing regimens or fixed-dose therapies.Conclusion: BMI is independently associated with increased risk of treatment failure in biologic-treated patients with UC, independent of dosing regimen.