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英夫利昔单抗对比阿达木单抗一线治疗克罗恩病肛周瘘的疗效优势。

Superior Efficacy of Infliximab Versus Adalimumab for First-Line Treatment of Crohn's Perianal Fistulae.

机构信息

Division of Gastroenterology & Hepatology, Johns Hopkins University School of Medicine, 4940 Eastern Avenue, Baltimore, MD, 21224, USA.

Division of Digestive Diseases, Center for Inflammatory Bowel Diseases, Vatche & Tamar Manoukian, UCLA School of Medicine, Los Angeles, CA, USA.

出版信息

Dig Dis Sci. 2023 Oct;68(10):3994-4000. doi: 10.1007/s10620-023-08060-7. Epub 2023 Aug 4.

DOI:10.1007/s10620-023-08060-7
PMID:37540392
Abstract

BACKGROUND

Crohn's disease perianal fistulae (CD-PAF) occur in 25% of patients and are notoriously challenging to manage. Tumor necrosis factor inhibitors are first line agents.

AIMS

The aim of this study was to compare infliximab (IFX) versus adalimumab (ADA) efficacy in CD-PAF healing over time.

METHODS

A retrospective study at two large-tertiary medical centers was performed. Inclusion criteria were actively draining CD-PAF and initial treatment with IFX or ADA following CD-PAF diagnosis. The primary endpoints were perianal fistula response and remission at 6 and 12 months. Secondary endpoints included biologic persistence over time and dose escalation at 6 and 12 months.

RESULTS

Among 151 patients included in the study, 92 received IFX and 59 received ADA as first line agents after CD-PAF diagnosis. At 6 months, the 64.9% of the IFX group and 34.8% of the ADA group demonstrated CD-PAF clinical improvement (p < 0.01). Univariate and multivariate analyses demonstrated significant differences among the IFX and ADA groups for clinical response at 6-months and 12-months (p = 0.002 and p = 0.042, respectively). There were no factors that predicted response, with the exception of concomitant immunomodulator affecting the 6-month clinical response (p = 0.021). Biologic persistence, characterized by Kaplan Meier methods, was significantly longer in the IFX group compared to the ADA group (Log-rank p = 0.01).

CONCLUSION

IFX induction and maintenance is associated with higher rates of response and remission in CD-PAF healing as well as higher treatment persistence compared to ADA. Additionally, our study supports the use of concomitant immunomodulator therapy for CD-PAF healing and remission.

摘要

背景

25%的克罗恩病患者会出现肛周瘘管(CD-PAF),其治疗极具挑战性。肿瘤坏死因子抑制剂是一线治疗药物。

目的

本研究旨在比较英夫利昔单抗(IFX)与阿达木单抗(ADA)在 CD-PAF 愈合过程中的疗效。

方法

本研究在两家大型三级医疗中心进行了回顾性研究。纳入标准为有引流的 CD-PAF,且在诊断后初始接受 IFX 或 ADA 治疗。主要终点为 6 个月和 12 个月时的肛周瘘管反应和缓解。次要终点包括生物制剂的持续时间和 6 个月和 12 个月时的剂量升级。

结果

在纳入研究的 151 例患者中,92 例接受 IFX,59 例接受 ADA 作为 CD-PAF 诊断后的一线治疗药物。6 个月时,IFX 组的 64.9%和 ADA 组的 34.8%患者的 CD-PAF 临床情况得到改善(p<0.01)。单因素和多因素分析显示,IFX 组和 ADA 组在 6 个月和 12 个月时的临床反应存在显著差异(p=0.002 和 p=0.042)。除了免疫调节剂会影响 6 个月的临床反应外(p=0.021),没有其他因素可以预测反应。生物制剂的持续时间用 Kaplan-Meier 方法进行评估,IFX 组显著长于 ADA 组(对数秩检验 p=0.01)。

结论

与 ADA 相比,IFX 诱导和维持治疗在 CD-PAF 愈合方面具有更高的反应和缓解率,以及更高的治疗持续时间。此外,本研究支持在 CD-PAF 愈合和缓解时使用免疫调节剂联合治疗。

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本文引用的文献

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World J Gastroenterol. 2022 Jun 21;28(23):2597-2608. doi: 10.3748/wjg.v28.i23.2597.
2
Higher Anti-tumor Necrosis Factor-α Levels Correlate With Improved Radiologic Outcomes in Crohn's Perianal Fistulas.较高的抗肿瘤坏死因子-α水平与克罗恩病肛周瘘管放射学结果改善相关。
Clin Gastroenterol Hepatol. 2022 Jun;20(6):1306-1314. doi: 10.1016/j.cgh.2021.07.053. Epub 2021 Aug 11.
3
Approach to medical therapy in perianal Crohn's disease.
肛周克罗恩病的医学治疗方法。
World J Gastroenterol. 2021 Jul 7;27(25):3693-3704. doi: 10.3748/wjg.v27.i25.3693.
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AGA Technical Review on the Medical Management of Moderate to Severe Luminal and Perianal Fistulizing Crohn's Disease.AGA 技术评论:中重度肠腔和肛旁瘘管型克罗恩病的医学管理
Gastroenterology. 2021 Jun;160(7):2512-2556.e9. doi: 10.1053/j.gastro.2021.04.023.
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Burden of disease and adaptation to life in patients with Crohn's perianal fistula: a qualitative exploration.克罗恩病肛周 fistula 患者的疾病负担和生活适应:定性探索。
Health Qual Life Outcomes. 2020 Nov 20;18(1):370. doi: 10.1186/s12955-020-01622-7.
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Effectiveness of Infliximab on Deep Radiological Remission in Chinese Patients with Perianal Fistulizing Crohn's Disease.英夫利昔单抗对中国肛周瘘管型克罗恩病患者深部放射学缓解的疗效。
Dig Dis Sci. 2021 May;66(5):1658-1668. doi: 10.1007/s10620-020-06398-w. Epub 2020 Jun 10.
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Higher anti-tumor necrosis factor levels are associated with perianal fistula healing and fistula closure in Crohn's disease.较高的抗肿瘤坏死因子水平与克罗恩病患者肛周瘘管愈合及瘘管闭合相关。
Eur J Gastroenterol Hepatol. 2020 Jan;32(1):32-37. doi: 10.1097/MEG.0000000000001561.
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