Impact of Immunogenicity on Clinical Outcomes in Patients With Moderate-to-Severe Inflammatory Bowel Disease Receiving Subcutaneous Infliximab: A Post Hoc Analysis of the LIBERTY Trials.

IF 6.7 2区医学 Q1 GASTROENTEROLOGY & HEPATOLOGY

United European Gastroenterology Journal Pub Date : 2026-04-01 DOI:10.1002/ueg2.70205

Jean-Frédéric Colombel, Silvio Danese, Stefan Schreiber, Bruce E Sands, Andres J Yarur, Aram Kang, Dong-Hyeon Kim, Young Nam Lee, Stephen B Hanauer

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引用次数: 0

Abstract

Background and aims: LIBERTY-CD and LIBERTY-UC demonstrated superior efficacy of subcutaneous infliximab (IFX SC) to placebo in patients with Crohn's disease (CD) or ulcerative colitis (UC). Here, we investigated the impact of anti-drug antibodies (ADAs) on clinical outcomes.

Methods: Patients randomized to IFX SC maintenance treatment in the LIBERTY trials were included (CD, n = 231; UC, n = 294). ADAs were tested using a highly sensitive, drug-tolerant assay. Patients were grouped by ADA occurrence and titer and evaluated for outcomes up to Week (W) 54.

Results: Among patients with CD and UC, 150 (64.9%) and 187 (63.6%) were ADA-positive, respectively. No statistically significant differences were observed between the ADA-positive and ADA-negative groups in W54 efficacy (CD: clinical remission, 69.5% [95% confidence interval: 61.6-77.5] vs. 79.7% [70.2-89.2], p = 0.134; endoscopic response, 57.5% [48.9-66.1] vs. 65.2% [54.0-76.5], p = 0.359; UC: clinical remission, 49.1% [41.3-56.8] vs. 57.0% [46.5-67.4], p = 0.284), drug persistence (CD: 84.7% [79.1-90.6] vs. 85.2% [77.8-93.3]; UC: 84.5% [79.5-89.8] vs. 77.6% [70.1-85.9]), and safety (patients with ≥ 1 treatment-emergent adverse event; CD: 71.2% [64.0-78.3] vs. 74.4% [64.9-83.8]; UC: 69.5% [62.9-76.0] vs. 64.2% [55.0-73.3]), despite lower drug concentrations in ADA-positive patients at W54 (CD: 10.6 μg/mL [9.1-12.2] vs. 17.9 μg/mL [15.8-20.1]; UC: 12.2 μg/mL [10.8-13.5] vs. 21.0 μg/mL [18.4-23.6]). No significant relationship between ADA titer and efficacy or persistence was noted.

Conclusions: Although ADAs affected drug levels, no significant differences by ADA occurrence were observed in W54 efficacy or safety among patients receiving IFX SC maintenance treatment. While high ADA titers were associated with lower drug levels, effectiveness was not diminished within 1 year.

Trial registration: ClinicalTrials.gov identifiers NCT03945019 (LIBERTY-CD) and NCT04205643 (LIBERTY-UC).

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免疫原性对接受皮下英夫利昔单抗治疗的中重度炎症性肠病患者临床结果的影响：LIBERTY试验的事后分析

背景和目的：liberity -CD和liberity -UC在克罗恩病（CD）或溃疡性结肠炎（UC）患者中，皮下英夫利昔单抗（IFX SC）的疗效优于安慰剂。在这里，我们研究了抗药物抗体（ADAs）对临床结果的影响。方法：纳入LIBERTY试验中随机接受IFX SC维持治疗的患者（CD, n = 231； UC, n = 294）。ADAs采用高度敏感的耐药试验进行检测。根据ADA的发生和滴度对患者进行分组，并评估到第54周的结果。结果：在CD和UC患者中，ada阳性分别为150例（64.9%）和187例（63.6%）。ada阳性组和ada阴性组在W54疗效（CD：临床缓解，69.5%[95%可信区间：61.6-77.5]比79.7% [70.2-89.2],p = 0.134；内镜下反应，57.5%[48.9-66.1]比65.2% [54.0-76.5],p = 0.359； UC：临床缓解，49.1%[41.3-56.8]比57.0% [46.5-67.4],p = 0.284）、药物持续性(CD: 84.7%[79.1-90.6]比85.2% [77.8-93.3]；尽管W54时ada阳性患者的药物浓度较低（CD: 10.6 μg/mL[9.1-12.2]对17.9 μg/mL [15.8-20.1]; UC: 12.2 μg/mL[10.8-13.5]对21.0 μg/mL [18.4-23.6]）， UC: 84.5%[79.5-89.8]对77.6%[70.1-85.9])和安全性（患者出现≥1次治疗引起的不良事件；CD: 71.2%[64.0-78.3]对74.4% [64.9-83.8];UC: 69.5%[62.9-76.0]对64.2%[55.0-73.3]）。ADA滴度与疗效或持久性无显著关系。结论：虽然ADA影响药物水平，但在接受IFX SC维持治疗的患者中，ADA的发生在W54疗效或安全性方面没有显著差异。虽然高ADA滴度与较低的药物水平相关，但1年内有效性并未降低。试验注册：ClinicalTrials.gov标识符NCT03945019 （LIBERTY-CD）和NCT04205643 （LIBERTY-UC）。

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来源期刊

United European Gastroenterology Journal GASTROENTEROLOGY & HEPATOLOGY-

CiteScore

10.50

自引率

13.30%

发文量

147

期刊介绍： United European Gastroenterology Journal (UEG Journal) is the official Journal of the United European Gastroenterology (UEG), a professional non-profit organisation combining all the leading European societies concerned with digestive disease. UEG’s member societies represent over 22,000 specialists working across medicine, surgery, paediatrics, GI oncology and endoscopy, which makes UEG a unique platform for collaboration and the exchange of knowledge.