Letter: Real-Life Evaluation of Effectiveness of Mesenchymal Stem Cell Treatment in Fistulising Crohn's Disease Emphasises the Importance of Appropriate Patient Selection and Centre Expertise

IF 6.6 1区 医学 Q1 GASTROENTEROLOGY & HEPATOLOGY
Weilun Gao, Jonathan P. Segal
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引用次数: 0

Abstract

Managing complex perianal fistulas in Crohn's disease is challenging as the condition is often refractory to conventional medical treatment strategies and surgery may be associated with significant compromise to quality of life [1]. The real-world retrospective multicentre cohort study by Bacsur et al. [2] offers promising results in the application of CX601 mesenchymal stem cell (MSC) treatment (Darvadstrocel). It is worth examining the superior results compared to two previous significant phase III multicentre randomised control trials by the ADMIRE-CD group [3, 4].

Bacsur et al. demonstrated higher rates of perianal clinical remission defined as closure of all treated fistulas (72.2% at W26 and 62.3% at W52) surpassing secondary endpoints in the treatment cohort of the ADMIRE CD trial (55% at W24) [3] and the more recent ADMIRE CD II trial treatment group (49.8% and 43.1% at W24 and W52, respectively) [4].

Several factors probably contributed to these improved outcomes. Differences in baseline disease severity and degree of prior advanced therapy use are key considerations. Patients in the ADMIRE-CD trials generally experienced longer delay during stable disease prior to commencing darvadstrocel (6 months vs. 3 months in Bacsur study) with longer established fistulas (draining for at least 6 weeks) and higher baseline mean Crohn's Disease Activity Index scores (88.7 vs. 51.1 in the Bacsur study). Moreover, ADMIRE CD excluded patients who had recently received corticosteroids, and had a higher proportion of baseline advanced therapy use (78% anti-TNF usage vs. 42.6% in Bacsur et al.), indicating a focus on patients with more severe disease [5].

The experience level of treating centres may also play a critical role. Bacsur et al. conducted their study in six high-volume centres, some with over 100 prior MSC administrations; ADMIRE CD treated 86 patients (vs. 223 in Bascur et al.) spanning 49 centres. This is in line with earlier findings from a Phase II trial that reported 71% fistula closure at 8 weeks focused in three specialised centres. This suggests the importance of centre expertise in allowing for precise MSC administration, post-procedural management and treatment success [6].

Variations in assessment methods of perianal fistula closure can also lead to disparities in reported results. ADMIRE CD employed masked gastroenterologists who used both visual inspection and manual compression to evaluate fistula closure rigorously [3] while the assessment criteria in the present study was not fully detailed. Moreover, in Bascur et al., treating colorectal surgeons were also allowed to participate in evaluating the outcomes in an un-masked fashion possibly introducing confirmation bias [7].

Bacsur et al. offers valuable insights into the real-world application of MSC therapy for Crohn's disease, underscoring the significance of patient selection, concurrent medication management, proficiency of the medical centre and the reassuring safety profile of MSC therapy. Although clinical trials like ADMIRE CD enforce rigorous standards, these are often impractical in real-world settings, where delays in patient care and complications from ceasing ongoing treatments are concerns. Future research in the real-world setting should be encouraged to offer more insight into this promising therapy.

Weilun Gao: writing – review and editing, writing – original draft, investigation. Jonathan P. Segal: conceptualization, writing – review and editing, supervision.

Jonathan P. Segal.

This article is linked to Bacsur et al papers. To view these articles, visit https://doi.org/10.1111/apt.18359 and https://doi.org/10.1111/apt.18432.

信:间充质干细胞治疗瘘管性克罗恩病的有效性的现实评估强调了适当的患者选择和中心专业知识的重要性
克罗恩病的复杂肛周瘘管的治疗是具有挑战性的,因为这种疾病通常难以用传统的药物治疗策略治疗,手术可能与生活质量的重大损害有关。Bacsur等人进行的真实世界回顾性多中心队列研究为CX601间充质干细胞(MSC)治疗(darvadstroel)的应用提供了有希望的结果。与之前由ADMIRE-CD组进行的两项重要的III期多中心随机对照试验相比,值得检查的是这些优越的结果[3,4]。Bacsur等人证明了更高的肛周临床缓解率,定义为所有治疗的瘘管闭合(W26时为72.2%,W52时为62.3%)超过了钦佩CD试验治疗队列(W24时为55%)[3]和最近的钦佩CD II试验治疗组(分别在W24和W52时为49.8%和43.1%)[3]的次要终点。有几个因素可能促成了这些改善的结果。基线疾病严重程度和先前高级治疗使用程度的差异是关键考虑因素。在ADMIRE-CD试验中,患者在开始使用达伐司特罗之前,在疾病稳定期间通常会经历更长的延迟(6个月,Bacsur研究为3个月),建立的瘘管时间更长(至少6周),基线平均克罗恩病活动指数评分更高(88.7比51.1 Bacsur研究)。此外,该研究排除了最近接受过皮质类固醇治疗的患者,并且使用基线高级治疗的比例更高(抗tnf使用比例为78%,Bacsur等为42.6%),表明该研究关注的是疾病更严重的患者。治疗中心的经验水平也可能发挥关键作用。Bacsur等人在六个高容量中心进行了他们的研究,其中一些中心有超过100次的MSC治疗;在49个中心,钦佩CD治疗了86例患者(Bascur等治疗了223例)。这与早期一项II期试验的结果一致,该试验报告了71%的瘘管在8周内关闭,集中在三个专业中心。这表明中心专业知识在允许精确的MSC管理,术后管理和治疗成功方面的重要性。不同的评估方法的肛瘘关闭也可能导致报告结果的差异。钦佩CD聘请蒙面胃肠病学家,他们使用目视检查和手动按压来严格评估瘘管闭合,而本研究的评估标准并未完全详细。此外,在Bascur等人的研究中,治疗结肠直肠外科医生也被允许以一种公开的方式参与评估结果,这可能会引入确认偏倚bbb。Bacsur等人对MSC治疗克罗恩病的实际应用提供了有价值的见解,强调了患者选择、同步用药管理、医疗中心熟练程度和MSC治疗令人放心的安全性的重要性。尽管像钦佩乳糜泻这样的临床试验执行了严格的标准,但在现实环境中,这些通常是不切实际的,因为患者护理的延迟和停止正在进行的治疗的并发症是令人担忧的。应该鼓励未来在现实环境中的研究,为这种有前途的疗法提供更多的见解。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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来源期刊
CiteScore
15.60
自引率
7.90%
发文量
527
审稿时长
3-6 weeks
期刊介绍: Alimentary Pharmacology & Therapeutics is a global pharmacology journal focused on the impact of drugs on the human gastrointestinal and hepato-biliary systems. It covers a diverse range of topics, often with immediate clinical relevance to its readership.
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