Biologics against tumor necrosis factor-α (TNF) and the p40 subunit of interleukin (IL)-12 and IL-23 are increasingly used in inflammatory bowel disease (IBD) treatment. However, information on response prediction to these agents is limited. Thus, we aimed to identify factors for IBD treatment response prediction.
We conducted a retrospective study in 33 IBD subjects for anti-TNF and a prospective study of 23 IBD and 11 non-IBD subjects for ustekinumab (UST). Mucosal biopsy specimens were obtained before treatment with biologics. The expression of 18 immune-related genes encoding representative cytokines and transcription factors was analyzed by quantitative polymerase chain reaction.
There was no difference between the treatment-resistant and -sensitive groups with regard to clinical characteristics. A higher expression of oncostatin M (OSM) and its receptor OSMR in the intestinal mucosa was most strongly associated with anti-TNF resistance, whereas lower IL23A expression was most strongly associated with UST resistance. In addition to the absolute expression levels of genes, concordant or discordant expression patterns of particular gene sets were associated with treatment sensitivity and resistance.
The association of anti-TNF resistance and mucosal OSM and OSMR expression was consistent with the results of a previous study in a European cohort. Our observation that IBD subjects with higher mucosal IL23A expression were more likely to achieve remission by UST has not been previously reported. The response to biologics may thus be predicted in IBD patients through the analysis of mucosal gene expression levels and patterns.
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The authors thank the staffs of endoscopy units at Kyushu Medical Center, Fukuoka Higashi Medical Center, Kitakyushu Municipal Medical Center, Saiseikai Fukuoka General Hospital, and Harasanshin Hospital for helpful discussions, and Dr. Junji Kishimoto (Center for Clinical and Translational Research, Kyushu University) for assistance with statistical analysis.
This study was supported in part by the Japan Society for the Promotion of Science KAKENHI (20K08389).
Conflict of interest
EI belongs to an endowed course supported by companies Ono Pharmaceutical Co., Ltd., Miyarisan Pharmaceutical Co. Ltd., Sanwa Kagaku Kenkyusho Co., Ltd., Otsuka Pharmaceutical Factory, Inc., Fujifilm Medical Co., Ltd., Terumo Corporation, Fancl FANCL Corporation, and Ohga Pharmacy. No other authors have any conflict of interest to report.
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Nishioka, K., Ogino, H., Chinen, T. et al. Mucosal IL23A expression predicts the response to Ustekinumab in inflammatory bowel disease. J Gastroenterol 56, 976–987 (2021). https://doi.org/10.1007/s00535-021-01819-7
- Inflammatory bowel disease
- Drug response prediction