I_MDS: an inflammatory bowel disease molecular activity score to classify patients with differing disease-driving pathways and therapeutic response to anti-TNF treatment

摘要

Author summary Patients exhibiting similar phenotypical characteristics, diagnosed with the same disease, exhibit variable response to therapeutics. This is a major health care issue, due to the increased patient suffering and the socioeconomical burden that occurs. Crohns disease and ulcerative colitis constitute good examples of inflammatory conditions, with sufferers responding differentially to existent therapeutics. Here, we identified disease-driving pathways and classified individuals into subpopulations that differ in their pathobiology and response to treatment. We utilized gene set variation analysis and transcriptomic data from inflammatory bowel disease sufferers to stratify patients at baseline or after anti-TNF treatment in clinical responders and non-responders. We explored gene signatures obtained from the literature, relevant to immune processes, which were significantly enriched in disease compared to healthy controls, as well as before and after treatment. Using these signatures, we established an inflammatory bowel disease molecular activity score, which allowed us to separate clinical responders and non-responders at baseline with high specificity and sensitivity. We validated the proposed approach in an independent data set, demonstrating comparable classification. This methodological approach may lead to better targeted design of clinical studies, allowing the selection of patient sharing similar underlying pathobiology, thus increasing the likelihood of clinical response to treatment.