摘要目的:评估维得利珠单克隆抗体（VDZ）治疗溃疡性结肠炎（UC）时出现继发性失应答（SLR）的影响因素。方法:采用回顾性队列研究方法。连续纳入南京大学医学院附属鼓楼医院2020年11月至2022年10月期间启动VDZ治疗的中度UC患者，均采用VDZ治疗4次及以上，在（22 ± 4）周时达到临床应答。根据随访期间是否发生SLR，将患者分为失应答组和持续应答组。比较两组临床资料的差异，采用单因素和多因素Cox回归模型分析SLR的影响因素。使用Kaplan-Meier曲线分析持续临床应答情况。结果:共纳入40例患者，男性21例，女性19例；用药年龄为（43.8 ± 15.5）岁；病程3.3（2.0，8.0）年；以E3全结肠型为主（62.5%）；改良Mayo评分为7（6，8）分；启动VDZ时合并使用糖皮质激素者17例（42.5%），合并5-氨基水杨酸者35例（87.5%）。29例患者在（22 ± 4）周时完成内镜评估，内镜缓解率为75.9%（22/29）。共有12例（30%）发生SLR，设为失应答组，余28例为持续应答组。启动用药后发生SLR的平均时间为（11.9 ± 5.9）个月。29例完成内镜评估患者中，失应答组和持续应答组（22 ± 4）周的内镜缓解率分别为42.9%（3/7）和86.4%（19/22），组间差异具有统计学意义（χ 2 = 5.489， P = 0.038）。单因素和多因素Cox回归分析结果显示，（22 ± 4）周内镜缓解是避免SLR的独立保护因素（ HR = 2.71，95% CI：1.30 ~ 5.62， P = 0.008）。Kaplan-Meier生存曲线显示，（22 ± 4）周内镜未缓解者较缓解者更易出现SLR（ OR = 2.71，95% CI：1.30 ~ 5.62， P = 0.042）。合并使用糖皮质激素的17例患者中，16例（94.1%）达到无激素缓解。12例失应答患者通过优化治疗和联用糖皮质激素后重获应答率为41.7%（5/12）。共8例（20%）患者在治疗过程中出现不良反应。 结论:对于采用VDZ治疗的中度UC患者，（22 ± 4）周时内镜缓解率越高，发生SLR的可能性越小。

abstractsObjective:To evaluate the influencing factors of secondary loss of response (SLR) in ulcerative colitis (UC) patients treated with vedolizumab (VDZ) .Methods:A retrospective cohort study was conducted. The patients with moderate UC who initiated VDZ treatment from November 2020 to October 2022 at Drum Tower Hospital of Nanjing University Medical College were included consecutively. They received VDZ treatment for at least 4 times and achieved clinical response at (22 ± 4) th week, and then were divided into the lost response group and sustained response group based on whether SLR occurred during follow-up period. Differences in clinical data between the two groups were compared, and influencing factors of SLR were analyzed by using univariate and multivariate Cox regression models. Kaplan-Meier curves were used to analyze the sustained clinical response.Results:A total of 40 UC patients were enrolled, including 21 males and 19 females. The average age of medication was (43.8 ± 15.5) years, with a disease course of 3.3 (2.0, 8.0) years. The extent was mainly E3 extensive UC type (62.5%) and modified Mayo score was 7 (6, 8) points. There were 17 patients (42.5%) using glucocorticoids and 35 patients (87.5%) using 5-aminosalicylic acid in combination of VDZ. A total of 29 patients completed endoscopic evaluation at (22 ± 4) th week, with a total endoscopic remission rate of 75.9% (22/29) . SLR occurred in 12 patients who were set as lost response group and the remaining 28 as sustained response group. The mean time from starting VDZ therapy to SLR occurrence was (11.9 ± 5.9) months. The endoscopic remission rates were 42.9% (3/7) in lost response group and 86.4% (19/22) in sustained response group and there was significant difference between the two groups (χ 2 = 5.489, P = 0.038) . Univariate and multivariate Cox regression analyses showed that endoscopic remission at (22 ± 4) th week was an independent protective factor against SLR ( HR = 2.71, 95% CI: 1.30-5.62, P = 0.008) . Kaplan-Meier survival curve demonstrated that patients who did not achieve endoscopic remission at (22 ± 4) th week were more likely to experience SLR ( OR = 2.71, 95% CI: 1.30-5.62, P = 0.042) . Among the 17 patients who received concomitant corticosteroids, 16 (94.1%) achieved steroid-free remission. In the lost response group, the rate of regaining response was 41.7% (5/12) through optimization of treatment and combination with corticosteroids. Eight patients (20%) experienced adverse reactions during the treatment. Conclusion:For moderate UC patients treated with VDZ, the higher endoscopic remission rate at (22 ± 4) th week, the lower incidence of SLR.