Department of Gastroenterology, University Hospital of Brest, Brest, France.
Nantes Université, CHU Nantes, Institut des Maladies de l'Appareil Digestif (IMAD), Hépato-Gastroentérologie, Inserm CIC 1413, Nantes, France.
PLoS One. 2024 Apr 2;19(4):e0298313. doi: 10.1371/journal.pone.0298313. eCollection 2024.
In patients with ulcerative colitis (UC), no biomarker is available to help the physician to choose the most suitable biotherapy. The primary objective of this pilot study was to assess the feasibility of identification of α4β7- and TNF-expressing cells, to predict the response to vedolizumab using confocal laser endoscopy (CLE).
Patients with moderate-to-severe UC, naïve of biotherapy, received vedolizumab. Clinical evaluation was performed at each infusion. Endoscopic evaluation was performed before inclusion and at week 22. Fresh colonic biopsies were stained using FITC-labelled vedolizumab and Alexa fluor-labelled adalimumab and ex vivo dual-band CLE images were acquired. Blood samples were collected to measure trough concentrations of vedolizumab and to determine absolute counts of T and B cells subpopulations, NK cells and monocytes.
Nineteen patients were enrolled in the study and received at least one dose of vedolizumab. Clinical remission and endoscopic improvement were observed in 58% of whom 5 patients (45%) had an endoscopic subscore of 0. In terms of clinical response and remission, endoscopic improvement and histologic response, FITC-conjugated vedolizumab staining tended to be higher in responder patients compared to non-responders at week 22. A threshold value of 6 positive FITC-vedolizumab staining areas detected by CLE seemed informative to discriminate the responders and non-responders. The results were similar in terms of clinical remission and endoscopic improvement with a sensitivity of 78% and a specificity of 85% (p = 0.05). Trough concentrations and blood immune cells were not associated with responses to vedolizumab.
This pilot study demonstrate that dual-band CLE is feasible to detect α4β7- and TNF-expressing cells. Positive α4β7 staining seems to be associated with clinical and endoscopic remission in UC patients treated by anti-α4β7-integrin, subject to validation by larger-scale studies. Clinical-trial.gov: NCT02878083.
在溃疡性结肠炎（UC）患者中，尚无生物标志物可帮助医生选择最合适的生物疗法。本初步研究的主要目的是评估使用共聚焦激光内镜（CLE）鉴定α4β7和 TNF 表达细胞以预测对 vedolizumab 反应的可行性。
接受 vedolizumab 治疗的中重度 UC 初治患者纳入研究。每次输注时均进行临床评估。在纳入前和第 22 周进行内镜评估。使用 FITC 标记的 vedolizumab 和 Alexa fluor 标记的 adalimumab 对新鲜结肠活检进行染色，并采集 ex vivo 双带 CLE 图像。采集血样以测量 vedolizumab 的谷浓度并确定 T 和 B 细胞亚群、NK 细胞和单核细胞的绝对计数。
19 例患者入组并至少接受了 1 次 vedolizumab 治疗。58%的患者观察到临床缓解和内镜改善，其中 5 例（45%）内镜亚评分 0。就临床缓解和临床缓解、内镜改善和组织学反应而言，与非应答者相比，应答者在第 22 周时 FITC 缀合的 vedolizumab 染色往往更高。CLE 检测到的 6 个阳性 FITC-vedolizumab 染色区域的阈值似乎可用于区分应答者和非应答者。在临床缓解和内镜改善方面，结果相似，敏感性为 78%，特异性为 85%（p=0.05）。vedolizumab 应答与谷浓度和血液免疫细胞无关。
这项初步研究表明，双带 CLE 可用于检测α4β7 和 TNF 表达细胞。阳性的α4β7 染色似乎与接受抗-α4β7 整联蛋白治疗的 UC 患者的临床和内镜缓解相关，尚需更大规模研究验证。Clinical-trial.gov：NCT02878083。
