Abstract
The most prominent treatment for the serious cases of Crohn’s disease (CD) are biological tumour necrosis factor (TNF) inhibitors. Unfortunately, therapy nonresponse is still a serious issue in ~1/3 of CD patients. Accurate prediction of responsiveness prior to therapy start would therefore be of great value. Clinical predictors have, however, proved insufficient. Here, we integrate genomic and expression data on potential pre-treatment biomarkers of anti-TNF nonresponse. We show that there is almost no overlap between genomic (annotated with tissue-specific expression quantitative trait loci data) and transcription (RNA and protein data) biomarkers. Furthermore, using interaction networks we demonstrate there is little direct interaction between the proposed biomarkers, though a majority do have common interactors connecting them into networks. Our gene ontology analysis shows that these networks have roles in apoptotic signalling, response to oxidative stress and inflammation pathways. We conclude that a more systematic approach with genome-wide search of genomic and expression biomarkers in the same patients is needed in future studies.
Highlights
Crohn’s disease (CD) is one of the two principal subtypes of Inflammatory Bowel Disease (IBD), a chronic autoimmune condition that may affect any part of the digestive system and seriously affects the quality of life [1,2,3]
The serious cases of CD/IBD are treated with biologicals, most prominently with tumour necrosis factor (TNF) inhibitors
The 9386 hits were either automatically excluded based on publication type or excluded after manual screening for obviously irrelevant studies and studies not reporting data on adult CD patients
Summary
Crohn’s disease (CD) is one of the two principal subtypes of Inflammatory Bowel Disease (IBD), a chronic autoimmune condition that may affect any part of the digestive system and seriously affects the quality of life [1,2,3]. 20–40% of patients (in clinical studies) fail to respond to treatment while 23–46% of patients loose response over time [4,5]. Non-responsiveness to anti-TNF therapy in CD is an important issue, both for patients who are exposed to potentially severe side-effects of the therapy that they do not benefit from, and for the healthcare systems that need to pay for the expensive yet inefficient treatment. With novel biologicals against alternative targets, such as ustekinumab (anti-IL12/23) and vedolizumab (anti-α4 β7 integrin) for treatment of CD/IBD and possibility of greater stratification of the patients [6], pre-emptive prediction of non-response to anti-TNF is becoming even more meaningful. Current clinical predictors of response to anti-TNFs do not satisfactorily predict the response. Genetic background and gene expression are under investigation [7,8,9,10,11,12,13]
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