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Serum albumin is the strongest predictor of anti-tumor necrosis factor nonresponse in inflammatory bowel disease in resource-constrained regions lacking therapeutic drug monitoring
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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 K. Singh, Karan Sachdeva, Raju Sharma, Nihar Ranjan Dash, Govind Makharia, Saurabh Kedia, Vineet Ahuja
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Intest Res 2023;21(4):460-470. Published online March 17, 2023
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DOI: https://doi.org/10.5217/ir.2022.00128
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Abstract
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- 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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Citations
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