Supplementary Material for: Histological Predictors for Therapeutic Response to Integrin Inhibitors in Patients with Ulcerative Colitis

Introduction: It is crucial to predict the effectiveness of advanced therapies before their administration in ulcerative colitis (UC). Only a few studies have revealed predictive histological factors. Here, we sought to determine whether conventional histology of pretreatment endoscopic biopsy specimens can predict the response to integrin inhibitors.
Methods: In the present single-center retrospective study, we examined histopathological findings before initiating an integrin inhibitor. Primary response (PR) was defined as a ≥3-point decrease in the partial Mayo score at 14 weeks. Logistic regression was used to identify the factors predictive for a PR.
Results: We analyzed 21 biological and Janus kinase inhibitor-naïve patients with UC. The median baseline Mayo score was 7 (IQR, 6–8), and the C-reactive protein was 0.36 (IQR 0.11–0.74). Histological findings included large lymphoid follicles (LF) in 61.9% (13/21), basal plasma cell infiltration (BP) in 52.4% (11/21), and eosinophilic infiltration (EO) in 42.9% (9/21). PR at 14 weeks was achieved in 54.1% (12/21). Among PR patients, LF was present in 91.7% (11/12), BP in 41.7% (5/12), and EO in 25.0% (3/12). PR was observed in 76.9% (10/13) of LF-positive patients vs. 12.5% (1/8) of LF-negative patients (p = 0.01). LF was significantly associated with the response to integrin inhibitors, whereas BP and EO were not.
Conclusion: The presence of LF in biopsy specimens predicts the response to integrin inhibitors in patients with UC. Conventional histological examinations may aid in predicting therapeutic responses to advanced therapies.

引言：在溃疡性结肠炎（ulcerative colitis, UC）患者接受先进疗法前，预判其治疗效果至关重要。目前仅有少数研究揭示了具有预测价值的组织学相关因素。本研究旨在探讨预处理内镜活检标本的常规组织学特征，是否能够预测整合素抑制剂（integrin inhibitors）的治疗应答情况。
方法：本项单中心回顾性研究中，我们于整合素抑制剂（integrin inhibitors）治疗开始前，对受试者的组织病理学特征进行了评估。主要应答（primary response, PR）定义为：治疗14周时部分Mayo评分较基线降低≥3分。采用logistic回归分析筛选与PR相关的预测因素。
结果：本研究共纳入21例未接受过生物制剂及Janus激酶抑制剂（Janus kinase inhibitor）治疗的溃疡性结肠炎患者。受试者基线部分Mayo评分中位数为7分（四分位间距IQR：6~8分），C反应蛋白（C-reactive protein）水平中位数为0.36（IQR：0.11~0.74）。组织病理学特征检出情况如下：大淋巴滤泡（large lymphoid follicles, LF）阳性率为61.9%（13/21），基底浆细胞浸润（basal plasma cell infiltration, BP）阳性率为52.4%（11/21），嗜酸性粒细胞浸润（eosinophilic infiltration, EO）阳性率为42.9%（9/21）。共有54.1%（12/21）的患者在治疗14周时达到PR。在达到PR的患者中，LF阳性者占91.7%（11/12），BP阳性者占41.7%（5/12），EO阳性者占25.0%（3/12）。LF阳性患者中76.9%（10/13）达到PR，而LF阴性患者中仅12.5%（1/8）达到PR（p=0.01）。LF与整合素抑制剂的治疗应答显著相关，而BP与EO则无此关联。
结论：活检标本中检出大淋巴滤泡（LF），可预测溃疡性结肠炎患者对整合素抑制剂的治疗应答情况。常规组织病理学检查或可辅助预判先进疗法的治疗应答效果。