Kumar Peeyush, Vuyyuru Sudheer K, Das Prasenjit, Kante Bhaskar, Ranjan Mukesh Kumar, Thomas David Mathew, Mundhra Sandeep, Sahu Pabitra, Venigalla Pratap Mouli, Jain Saransh, Goyal Sandeep, Golla Rithvik, Virmani Shubi, Singh Mukesh K, Sachdeva Karan, Sharma Raju, Dash Nihar Ranjan, Makharia Govind, Kedia Saurabh, Ahuja Vineet
Department of Gastroenterology and Human Nutrition, All India Institute of Medical Sciences, New Delhi, India.
Department of Pathology, All India Institute of Medical Sciences, New Delhi, India.
Intest Res. 2023 Oct;21(4):460-470. doi: 10.5217/ir.2022.00128. Epub 2023 Mar 17.
BACKGROUND/AIMS: Evidence on predictors of primary nonresponse (PNR), and secondary loss of response (SLR) to anti-tumor necrosis factor (anti-TNF) agents in inflammatory bowel disease is scarce from Asia. We evaluated clinical/biochemical/molecular markers of PNR/SLR in ulcerative colitis (UC) and Crohn's disease (CD).
Inflammatory bowel disease patients treated with anti-TNF agents (January 2005-October 2020) were ambispectively included. Data concerning clinical and biochemical predictors was retrieved from a prospectively maintained database. Immunohistochemistry for expression of oncostatin M (OSM), OSM receptor (OSM-R), and interleukin-7 receptor (IL-7R) were done on pre anti-TNF initiation mucosal biopsies.
One-hundred eighty-six patients (118 CD, 68 UC: mean age, 34.1±13.7 years; median disease duration at anti-TNF initiation, 60 months; interquartile range, 28-100.5 months) were included. PNR was seen in 17% and 26.5% and SLR in 47% and 28% CD and UC patients, respectively. In CD, predictors of PNR were low albumin (P<0.001), postoperative recurrence (P=0.001) and high IL-7R expression (P<0.027) on univariate; and low albumin alone (hazard ratio [HR], 0.09; 95% confidence interval [CI], 0.03-0.28; P<0.001) on multivariate analysis respectively. Low albumin (HR, 0.31; 95% CI, 0.15-0.62; P=0.001) also predicted SLR. In UC, predictors of PNR were low albumin (P<0.001), and high C-reactive protein (P<0.001), OSM (P<0.04) and OSM-R (P=0.07) stromal expression on univariate; and low albumin alone (HR, 0.11; 95% CI, 0.03-0.39; P=0.001) on multivariate analysis respectively.
Low serum albumin at baseline significantly predicted PNR in UC and PNR/SLR in CD patients. Mucosal markers of PNR were high stromal OSM/OSM-R in UC and high IL-7R in CD patients.
背景/目的：亚洲地区关于炎症性肠病患者对抗肿瘤坏死因子（抗TNF）药物原发性无反应（PNR）和继发性反应丧失（SLR）预测因素的证据较少。我们评估了溃疡性结肠炎（UC）和克罗恩病（CD）患者PNR/SLR的临床/生化/分子标志物。
纳入2005年1月至2020年10月期间接受抗TNF药物治疗的炎症性肠病患者。从一个前瞻性维护的数据库中检索有关临床和生化预测因素的数据。在开始抗TNF治疗前的黏膜活检组织上进行抑瘤素M（OSM）、OSM受体（OSM-R）和白细胞介素-7受体（IL-7R）表达的免疫组织化学检测。
共纳入186例患者（118例CD，68例UC；平均年龄34.1±13.7岁；开始抗TNF治疗时的疾病中位病程为60个月；四分位间距为28 - 100.5个月）。CD和UC患者中PNR发生率分别为17%和26.5%，SLR发生率分别为47%和28%。在CD中，单因素分析显示PNR的预测因素为低白蛋白（P<0.001）、术后复发（P=0.001）和高IL-7R表达（P<0.027）；多因素分析显示仅低白蛋白（风险比[HR]，0.09；95%置信区间[CI]，0.03 - 0.28；P<0.001）是PNR的预测因素。低白蛋白（HR，0.31；95% CI，0.15 - 0.62；P=0.001）也是SLR的预测因素。在UC中，单因素分析显示PNR的预测因素为低白蛋白（P<0.001）、高C反应蛋白（P<0.001）、高OSM（P<0.04）和OSM-R基质表达（P=0.07）；多因素分析显示仅低白蛋白（HR，0.11；95% CI，0.03 - 0.39；P=0.001）是PNR的预测因素。
基线时低血清白蛋白显著预测UC患者的PNR以及CD患者的PNR/SLR。UC患者PNR的黏膜标志物是高基质OSM/OSM-R，CD患者是高IL-7R。
