BACKGROUND & AIMS Gut-homing lymphocytes that express the integrin α4β7 and CCR9 might contribute to development of primary sclerosing cholangitis (PSC). Vedolizumab, which blocks the integrin α4β7, is used to treat patients with inflammatory bowel diseases (IBD), but there are few data on its efficacy in patients with PSC. We investigated the effects of vedolizumab in a large international cohort of patients with PSC and IBD. METHODS We collected data from European and North American centers participating in the International PSC Study Group from patients with PSC and IBD who received at least 3 doses of vedolizumab (n = 102; median vedolizumab treatment duration, 412 days). Demographic and clinical data were collected from baseline and during the follow-up period (until liver transplantation, death, or 56 days after the final vedolizumab infusion). We analyzed overall changes in biochemical features of liver and proportions of patients with reductions in serum levels of alkaline phosphatase (ALP) of 20% or more, from baseline through last follow-up evaluation. Other endpoints included response of IBD to treatment (improved, unchanged, or worsened, judged by the treating clinician, as well as endoscopic score) and liver-related outcomes. RESULTS In the entire cohort, the median serum level of ALP increased from 1.54-fold the upper limit of normal at baseline to 1.64-fold the upper limit of normal at the last follow-up examination (P = .018); serum levels of transaminases and bilirubin also increased by a small amount between baseline and the last follow-up examination. Serum levels of ALP decreased by 20% or more in 21 patients (20.6%); only the presence of cirrhosis (odds ratio, 4.48; P = .019) was independently associated with this outcome. Of patients with available endoscopic data, 56.8% had a response of IBD to treatment. Liver-related events occurred in 21 patients (20.6%), including bacterial cholangitis, cirrhosis decompensation, or transplantation. CONCLUSIONS In an analysis of patients with PSC and IBD in an international study group, we found no evidence for a biochemical response to vedolizumab, although serum level of ALP decreased by 20% or more in a subset of patients. Vedolizumab appears to be well tolerated and the overall response of IBD was the same as expected for patients without PSC.

中文翻译：

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维多珠单抗对原发性硬化性胆管炎和炎性肠病患者的影响。

背景与目的表达整联蛋白α4β7和CCR9的肠归巢淋巴细胞可能有助于原发性硬化性胆管炎（PSC）的发展。阻断整合素α4β7的维多珠单抗用于治疗炎症性肠病（IBD）患者，但有关其对PSC患者疗效的数据很少。我们调查了vedolizumab在PSC和IBD患者的大型国际队列中的作用。方法我们从参加国际PSC研究小组的欧洲和北美中心收集了接受至少3剂维多珠单抗（n = 102；维多珠单抗中位治疗时间412天）的PSC和IBD患者的数据。从基线和随访期间（直到肝移植，死亡，或最后一次维多珠单抗输注后56天）。从基线到最后的随访评估，我们分析了肝脏生化特征的总体变化以及血清碱性磷酸酶（ALP）血清水平降低20％或更多的患者比例。其他终点包括IBD对治疗的反应（由治疗临床医师判断为改善，不变或恶化，以及内窥镜评分）和肝脏相关结局。结果在整个队列中，ALP的中位血清水平从基线时的正常上限的1.54倍增加到上次随访检查时的正常上限的1.64倍（P = .018）；从基线到上次随访检查之间，转氨酶和胆红素的血清水平也有少量升高。21名患者的血清ALP水平降低了20％或更多（20.6％）；只有肝硬化的存在（优势比为4.48； P = .019）与该结果独立相关。在有可用内窥镜检查数据的患者中，有56.8％的患者对治疗有IBD反应。肝相关事件发生在21例患者中（20.6％），包括细菌性胆管炎，肝硬化失代偿或移植。结论在一个国际研究小组的PSC和IBD患者分析中，我们发现没有证据表明对维多珠单抗有生化反应，尽管一部分患者的ALP血清水平降低了20％或更多。Vedolizumab似乎具有良好的耐受性，IBD的总体反应与无PSC的患者预期的相同。8％的患者对治疗的IBD有反应。肝相关事件发生在21例患者中（20.6％），包括细菌性胆管炎，肝硬化失代偿或移植。结论在一个国际研究小组的PSC和IBD患者分析中，我们发现没有证据表明对维多珠单抗有生化反应，尽管一部分患者的ALP血清水平降低了20％或更多。Vedolizumab似乎具有良好的耐受性，IBD的总体反应与无PSC的患者预期的相同。8％的患者对治疗的IBD有反应。肝相关事件发生在21例患者中（20.6％），包括细菌性胆管炎，肝硬化失代偿或移植。结论在一个国际研究小组的PSC和IBD患者分析中，我们发现没有证据表明对维多珠单抗有生化反应，尽管一部分患者的ALP血清水平降低了20％或更多。Vedolizumab似乎具有良好的耐受性，IBD的总体反应与无PSC的患者预期的相同。尽管一部分患者的血清ALP水平降低了20％或更多。Vedolizumab似乎具有良好的耐受性，IBD的总体反应与无PSC的患者预期的相同。尽管一部分患者的血清ALP水平降低了20％或更多。Vedolizumab似乎具有良好的耐受性，IBD的总体反应与无PSC的患者预期的相同。