Department of Gastroenterology, Sheba Medical Center, Tel-Aviv, Israel.
Sackler School of Medicine, Tel-Aviv University, Tel-Aviv ; Israel.
J Crohns Colitis. 2017 May 1;11(5):549-555. doi: 10.1093/ecco-jcc/jjw182.
The association of infliximab [IFX] trough levels with clinical and endoscopic outcomes in inflammatory bowel disease is well established. However, there is scarce data regarding the association of perianal fistula response with IFX. The aim of this study was to establish whether early induction infliximab levels and anti-infliximab antibodies [ATIs] are associated with perianal fistula response.
Consecutive CD patients with perianal fistulae that were treated with IFX between 2008 and 2016 were included in the study. Response was defined as cessation or significant improvement of fistula drainage. Patients with unavailable IFX level or ATI measurements and/or missing clinical follow-up at Week 14 were excluded.
A total of 36 patients with perianal fistulae were included; 25/36 [69.4%] responded to treatment by Week 14. The median induction IFX levels at Weeks 2, 6 and 14 in the responders group at Week 14 were higher compared with those of the non-responders group [20/5.6 µg/mL, P = 0.0001; 13.3/2.55 µg/mL P = 0.0001; 4.1/0.14 µg/mL, P = 0.01]. On multivariate analysis, IFX leve at Weeks 2 and 6 were significantly associated with fistula response at Weeks 14 and 30. IFX drug levels of 9.25 µg/mL at Week 2 and 7.25 µg/mL at Week 6 were the best predictors of fistula response.
High IFX trough levels during induction are associated with favorable fistula response to anti-TNF treatment. If validated in a larger prospective study, our findings may help guide anti-TNF treatment in patients with perianal CD, and suggest serum level-guided treatment escalation in non-responders or prompt changing of biologic treatment in non-responders.
英夫利昔单抗（IFX）的药物谷浓度与炎症性肠病的临床和内镜结果之间的关系已得到充分证实。然而，关于肛周瘘管反应与 IFX 之间的关系的数据却很少。本研究旨在确定早期诱导 IFX 水平和抗 IFX 抗体（ATI）是否与肛周瘘管反应相关。
本研究纳入了 2008 年至 2016 年间接受 IFX 治疗的患有肛周瘘管的 CD 患者。反应定义为瘘管引流的停止或显著改善。排除了无法获得 IFX 水平或 ATI 测量值和/或在第 14 周时缺少临床随访的患者。
共纳入 36 例肛周瘘管患者；在第 14 周时，有 25/36（69.4%）例患者对治疗有反应。在第 14 周时，应答组患者在第 2、6 和 14 周的诱导 IFX 水平中位数高于无应答组[20/5.6 µg/mL，P=0.0001；13.3/2.55 µg/mL，P=0.0001；4.1/0.14 µg/mL，P=0.01]。在多变量分析中，第 2 周和第 6 周的 IFX 水平与第 14 周和第 30 周的瘘管反应显著相关。第 2 周时 IFX 药物水平为 9.25 µg/mL，第 6 周时 IFX 药物水平为 7.25 µg/mL，是预测瘘管反应的最佳指标。
诱导期 IFX 的药物谷浓度高与抗 TNF 治疗对瘘管的良好反应相关。如果在更大的前瞻性研究中得到验证，我们的发现可能有助于指导 CD 患者的抗 TNF 治疗，并提示在无应答者中进行基于血清水平的治疗升级或在无应答者中及时更换生物治疗。
