Department of Gastroenterology, Sackler School of Medicine, Sheba Medical Center Tel Hashomer, Tel-Aviv University, Tel Aviv, Israel.
First Affiliated Hospital of Sun-Yatsen University, Guangzhou, China.
Aliment Pharmacol Ther. 2018 Apr;47(8):1117-1125. doi: 10.1111/apt.14567. Epub 2018 Feb 15.
Data on combination-biologic treatment in (IBD) are still scant.
To explore outcomes of patients co-exposed to anti-TNF and vedolizumab.
Patients starting vedolizumab having measurable anti-TNF levels after recently stopping adalimumab/infliximab ('VDZ-aTNF' group), were compared with control vedolizumab patients in a retrospective 1:2 matched case-control study.
Seventy-five patients were included (25 VDZ-aTNF, 50 VDZ). Adverse events were experienced by 9/25 VDZ-aTNF compared to 13/50 VDZ patients (P = 0.4, follow-up 14 weeks in all). Week 14 clinical remission was attained in 10/25 (40%) of VDZ-aTNF patients versus 23/50 (46%) of VDZ patients (OR = 0.8, 95% CI 0.3-2.1, P = 0.6) and clinical response in 19/25 (76%) versus 39/50 (78%) respectively (OR = 0.9, 95% CI 0.3-2.7, P = 0.8). Corticosteroid-free remission and corticosteroid-free response were experienced by 30% and 54%, respectively, of the entire cohort, and were similar between the two groups. Vedolizumab drug concentrations at week 2, 6 and 14 were similar among VDZ-aTNF and VDZ patients (P > 0.5). Multi-variable analysis showed independent association of some vedolizumab drug-levels time-points with baseline albumin and weight, but not with anti-TNF co-exposure. In a prospective study of a separate cohort of patients starting infliximab (n = 12), the percentage of α4β7+ memory T cells, slightly but nonsignificantly increased throughout weeks 0, 2 to 14 (26 ± 2.3%, 27.8 ± 2.9%, 29.5 ± 2.6% respectively, P = 0.06).
Vedolizumab/anti-TNF co-exposure did not generate new safety signals during 14-weeks induction, nor did it reduce efficacy or alter vedolizumab pharmacokinetics. These observations may aid the design of future co-biologics trials and also suggest that a deliberate waiting-interval between anti-TNF cessation and subsequent vedolizumab initiation may not be warranted.
（IBD）中联合生物制剂治疗的数据仍然很少。
探索同时暴露于抗 TNF 和 vedolizumab 的患者的结局。
在回顾性 1:2 匹配病例对照研究中，比较了最近停用阿达木单抗/英夫利昔单抗后仍有可测量抗 TNF 水平的开始使用 vedolizumab 的患者（“VDZ-aTNF”组）与对照 vedolizumab 患者。
共纳入 75 例患者（25 例 VDZ-aTNF，50 例 VDZ）。与 50 例 VDZ 患者中的 13 例（P = 0.4，所有患者随访 14 周）相比，25 例 VDZ-aTNF 患者中有 9 例出现不良事件。第 14 周时，25 例 VDZ-aTNF 患者中有 10 例（40%）达到临床缓解，50 例 VDZ 患者中有 23 例（46%）（OR = 0.8，95%CI 0.3-2.1，P = 0.6），25 例 VDZ-aTNF 患者中有 19 例（76%）达到临床应答，50 例 VDZ 患者中有 39 例（78%）（OR = 0.9，95%CI 0.3-2.7，P = 0.8）。整个队列中分别有 30%和 54%的患者达到无皮质激素缓解和无皮质激素应答，两组之间无差异。第 2、6 和 14 周时，VDZ-aTNF 和 VDZ 患者的 vedolizumab 药物浓度相似（P > 0.5）。多变量分析显示，某些 vedolizumab 药物水平时间点与基线白蛋白和体重独立相关，但与抗 TNF 联合暴露无关。在开始使用英夫利昔单抗的另一组患者的前瞻性研究中（n = 12），α4β7+记忆 T 细胞的百分比在 0 至 14 周期间略有但无统计学意义的增加（分别为 26 ± 2.3%、27.8 ± 2.9%、29.5 ± 2.6%，P = 0.06）。
在 14 周诱导期间，vedolizumab/抗 TNF 联合暴露未产生新的安全性信号，也未降低疗效或改变 vedolizumab 药代动力学。这些观察结果可能有助于设计未来的联合生物制剂试验，也表明在抗 TNF 停药和随后开始使用 vedolizumab 之间故意等待间隔可能没有必要。
