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.

克罗恩病中复杂的肛周瘘管的治疗具有挑战性，因为这种疾病通常对常规药物治疗策略无效，并且手术可能与生活质量的严重损害有关[1]。Bacsur 等人 [2] 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 （Darvadstrocel） 的应用提供了有希望的结果。与 ADMIRE-CD 组之前两项重要的 III 期多中心随机对照试验相比，值得研究其优越的结果 [3， 4]。

Bacsur 等人证明，肛周临床缓解率更高，定义为所有治疗瘘管闭合（第 26 周为 72.2%，第 52 周为 62.3%），超过了 ADMIRE CD 试验治疗队列中的次要终点（第 24 周为 55%）[3] 和最近的 ADMIRE CD II 试验治疗组（第 24 周和第 52 周为 49.8% 和 43.1%）， 分别）[4]。

有几个因素可能有助于这些改善的结局。基线疾病严重程度和既往先进治疗使用程度的差异是关键考虑因素。ADMIRE-CD 试验中的患者在开始 darvadstrocel 之前（6 个月，Bacsur 研究中为 3 个月）在病情稳定期间通常会经历更长的延迟，瘘管建立时间更长（引流至少 6 周）和更高的基线平均克罗恩病活动指数评分（88.7 vs. Bacsur 研究中为 51.1）。此外，ADMIRE CD 排除了最近接受皮质类固醇治疗的患者，并且基线晚期治疗使用比例更高（抗 TNF 使用率为 78%，而 Bacsur 等人为 42.6%），表明关注病情更严重的患者 [5]。

治疗中心的经验水平也可能起关键作用。Bacsur 等人在六个高容量中心进行了他们的研究，其中一些中心之前有 100 多次 MSC 给药;ADMIRE CD 治疗了 86 名患者（Bascur 等人为 223 名），跨越 49 个中心。这与 II 期试验的早期结果一致，该试验报告了 71% 的瘘管闭合在 8 周，重点关注三个专业中心。这表明中心专业知识在实现精确的 MSC 给药、术后管理和治疗成功方面的重要性 [6]。

肛周瘘闭合评估方法的差异也可能导致报告结果的差异。ADMIRE CD 聘请了蒙面胃肠病学家，他们使用肉眼检查和手动按压来严格评估瘘管闭合 [3]，而本研究中的评估标准并未完全详细说明。此外，在 Bascur 等人中，治疗结直肠外科医生也被允许以未掩蔽的方式参与评估结果，这可能会引入确认偏倚 [7]。

Bacsur 等人对 MSC 疗法在克罗恩病中的实际应用提供了宝贵的见解，强调了患者选择、同步用药管理、医疗中心的熟练程度以及 MSC 疗法令人放心的安全性的重要性。尽管像 ADMIRE CD 这样的临床试验执行严格的标准，但在现实世界中，这些标准通常是不切实际的，因为在现实世界中，患者护理的延误和停止正在进行的治疗引起的并发症是令人担忧的。应鼓励未来在现实世界环境中进行研究，以对这种有前途的疗法提供更多见解。