Serum albumin is the strongest predictor of anti-tumor necrosis factor nonresponse in inflammatory bowel disease in resource-constrained regions lacking therapeutic drug monitoring.

IF 3.4 Q2 GASTROENTEROLOGY & HEPATOLOGY Intestinal Research Pub Date : 2023-10-01 Epub Date: 2023-03-17 DOI:10.5217/ir.2022.00128

Peeyush Kumar, Sudheer K Vuyyuru, Prasenjit Das, Bhaskar Kante, Mukesh Kumar Ranjan, David Mathew Thomas, Sandeep Mundhra, Pabitra Sahu, Pratap Mouli Venigalla, Saransh Jain, Sandeep Goyal, Rithvik Golla, Shubi Virmani, Mukesh Singh, Karan Sachdeva, Raju Sharma, Nihar Ranjan Dash, Govind Makharia, Saurabh Kedia, Vineet Ahuja

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Abstract

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).

Methods: 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.

Results: 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.

Conclusions: 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.

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在缺乏治疗药物监测的资源受限地区，血清白蛋白是炎症性肠病中抗肿瘤坏死因子无反应的最强预测因子。

背景/目的：亚洲很少有证据表明炎症性肠病对抗肿瘤坏死因子（anti-TNF）药物的原发性无反应（PNR）和继发性反应丧失（SLR）的预测因素。我们评估了溃疡性结肠炎（UC）和克罗恩病（CD）中PNR/SLR的临床/生化/分子标志物。方法：分别纳入接受抗TNF药物治疗的炎症性肠病患者（2005年1月至2020年10月）。从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。在抗TNF启动前的粘膜活检中进行了肿瘤学抑制素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。结果：一百八十六名患者（118名CD，68名UC：平均年龄，34.1±13.7岁；抗TNF起始时的中位疾病持续时间为60个月；四分位间距为28-100.5个月）被纳入。PNR分别见于17%和26.5%，SLR分别见于47%和28%的CD和UC患者。在CD中，PNR的预测因子是低白蛋白（P结论：基线时的低血清白蛋白显著预测UC的PNR和CD患者的PNR/SLR。PNR的粘膜标志物是UC的高基质OSM/OSM-R和CD病人的高IL-7R。

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来源期刊

Intestinal Research GASTROENTEROLOGY & HEPATOLOGY-

CiteScore

7.40

自引率

10.20%

发文量

审稿时长

38 weeks

期刊介绍： Intestinal Research (Intest Res) is the joint official publication of the Asian Organization for Crohn''s and Colitis (AOCC), Chinese Society of IBD (CSIBD), Japanese Society for IBD (JSIBD), Korean Association for the Study of Intestinal Diseases (KASID), Taiwan Society of IBD (TSIBD) and Colitis Crohn''s Foundation (India) (CCF, india). The aim of the Journal is to provide broad and in-depth analysis of intestinal diseases, especially inflammatory bowel disease, which shows increasing tendency and significance. As a Journal specialized in clinical and translational research in gastroenterology, it encompasses multiple aspects of diseases originated from the small and large intestines. The Journal also seeks to propagate and exchange useful innovations, both in ideas and in practice, within the research community. As a mode of scholarly communication, it encourages scientific investigation through the rigorous peer-review system and constitutes a qualified and continual platform for sharing studies of researchers and practitioners. Specifically, the Journal presents up-to-date coverage of medical researches on the physiology, epidemiology, pathophysiology, clinical presentations, and therapeutic interventions of the intestinal diseases. General topics of interest include inflammatory bowel disease, colon and small intestine cancer or polyp, endoscopy, irritable bowel syndrome and other motility disorders, infectious enterocolitis, intestinal tuberculosis, and so forth. The Journal publishes diverse types of academic materials such as editorials, clinical and basic reviews, original articles, case reports, letters to the editor, brief communications, perspective, statement or commentary, and images that are useful to clinicians and researchers.