Shani Uria, State Monica, Mateescu Radu Bogdan, Davidoiu Ana-Maria, Negreanu Lucian, Silva Isabel, Magro Fernando, Lees Charlie W, Plevris Nikolas, Roblin Xavier, Castellet-Farrús Sílvia, Gonzalez Lama Yago, Wang Shanshan, Abad Carolina, Imperatore Nicola, Lukas Milan, Vojtechova Gabriela, Ukashi Offir, Ben-Horin Shomron, Nancey Stephane, Savarino Edoardo, Stawczyk-Eder Kamila, Eder Piotr, Toskas Alexandros, Kamperidis Nikolaos, Arebi Naila, Farkas Bernadett, Farkas Klaudia, Pipek Barbora, Falt Premysl, Karmiris Konstantinos, Nikolaou Pinelopi, Krznaric Zeljko, Brinar Marko, Hoentjen Frank, van Lierop Lisa, Barreiro-de Acosta Manuel, Zaborowska Marta, Zagorowicz Edyta, Pugliese Daniela, Cuccia Giuseppe, Truyens Marie, Kopylov Uri
Department of Internal Medicine B, Sheba Medical Center, Tel Hashomer, Ramat Gan, Israel.
Gastroenterology Department, Colentina Clinical Hospital, Carol Davila University of Medicine and Pharmacy, Bucharest, Romania.
J Crohns Colitis. 2025 Jun 4;19(6). doi: 10.1093/ecco-jcc/jjaf099.
Anti-tumor necrosis factor-α inhibitors (anti-TNFs) are the established treatment for perianal Crohn's disease (pCD), but relapse and non-response are common. Data on second- and third-line biologics are limited. We present the first direct comparison of second- and third-line biologics in pCD patients with active perianal disease previously treated with first-line anti-TNFs.
A multicenter retrospective cohort study included adult patients with pCD who failed first-line anti-TNF. The primary outcome was clinical perianal response, with secondary outcomes of radiological response (magnetic resonance imaging or transrectal ultrasound) and healing, and clinical remission. Propensity score matching (PSM) was used to adjust for baseline differences.
A total of 486 pCD patients from 23 IBD centers were included, with 333/486 (68.5%) and 216/263 (82.1%) matched by PSM in the second and third-line treatment groups, respectively. In the second-line group, 62/78 (79.5%) of ustekinumab (UST)-treated patients achieved clinical perianal response, compared to 46/78 (58.9%) with vedolizumab (VDZ) (OR 4.47, 95% CI, 1.94-10.28, P < .001) and 38/78 (48.7%) with anti-TNFs (OR 5.29, 95% CI, 2.39-11.71, P < .001). In the third-line group, 38/49 (77.6%) of UST-treated patients achieved clinical perianal response, compared to 29/49 (59.2%) with VDZ (OR 9.96, 95% CI, 2.6-38.4, P < .001) and 27/49 (55.1%) with anti-TNFs (OR 12.03, 95% CI, 2.99-48.47, P < .001). UST-treated patients also had higher radiological response rates than VDZ (OR 3.28, 95% CI, 1.07-10.07, P = .038).
In pCD patients failing anti-TNFs as first-line treatment, ustekinumab may be more effective than vedolizumab or another anti-TNF as second or third-line therapy.
抗肿瘤坏死因子-α抑制剂（抗TNF药物）是肛周克罗恩病（pCD）的既定治疗方法，但复发和无反应情况很常见。关于二线和三线生物制剂的数据有限。我们首次对先前接受一线抗TNF药物治疗且患有活动性肛周疾病的pCD患者的二线和三线生物制剂进行了直接比较。
一项多中心回顾性队列研究纳入了一线抗TNF治疗失败的成年pCD患者。主要结局是肛周临床反应，次要结局包括放射学反应（磁共振成像或经直肠超声）、愈合情况以及临床缓解。采用倾向评分匹配（PSM）来调整基线差异。
共纳入了来自23个炎症性肠病中心的486例pCD患者，二线和三线治疗组分别有333/486（68.5%）和216/263（82.1%）通过PSM进行了匹配。在二线治疗组中，接受优特克单抗（UST）治疗的患者有62/78（79.5%）达到肛周临床反应，而接受维多珠单抗（VDZ）治疗的患者为46/78（58.9%）（比值比4.47，95%置信区间，1.94 - 10.28，P <.001），接受抗TNF药物治疗的患者为38/78（48.7%）（比值比5.29，95%置信区间，2.39 - 11.71，P <.001）。在三线治疗组中，接受UST治疗的患者有38/49（77.6%）达到肛周临床反应，而接受VDZ治疗的患者为29/49（59.2%）（比值比9.96，95%置信区间，2.6 - 38.4，P <.001），接受抗TNF药物治疗的患者为27/49（55.1%）（比值比12.03，95%置信区间，2.99 - 48.47，P <.001）。接受UST治疗的患者放射学反应率也高于VDZ（比值比3.28，95%置信区间，1.07 - 10.07，P = 0.038）。
在一线治疗使用抗TNF药物失败的pCD患者中，优特克单抗作为二线或三线治疗可能比维多珠单抗或另一种抗TNF药物更有效。
