Influence of JAK inhibitors on the disease-associated network of intestinal immune cells in ulcerative colitis

The treatment for Ulcerative Colitis (UC) aims to achieve and maintain
remission and is usually lifelong and expensive. Current available medications
are unable to break the cycle of chronic inflammation, and still a significant
proportion of patients will fail to respond (primary non-response) or lose
response over time (secondary non-response). There is now growing evidence that
there is substantial interpatient variation in the composition of the
inflammation associated network of immune cells. A deeper knowledge of the
patient*s alterations in the mucosal immune response would help identify key
drivers of inflammation and select the appropriate therapy. By analyzing the
changes in the composition of immune cells induced by Janus Kinase (JAK)
inhibition, we aim to obtain a better insight into the mechanistic effects of
JAK inhibition and the downstream effects. These mechanistic insights are
needed to identifying potential responders and non-responders in the future.

Observing changes in immune cell composition in locally (intestinal biopsies)
and systemically (Peripheral Blood Mononuclear Cells (PBMCs)) upon JAK
inhibitor treatment of UC patients.

Patient with active ulcerative colitis that are eligible for medication change
will and choose for a JAK inhibitor will be asked to participate. The choice
for specific medication is at the gastroenterologists and patients discretion.
The follow-up will be according to standard clinical practice. At all endoscopy
timepoints we will acquire extra biopsies to perform multi-omics analyses (the
multi-omics approach is explained in section 1, the introduction). We will
obtain PMBCs at the standard care blood control time points. The PBMCs will
also be used for multi-omics analyses.

In adults there is a negligible risk to taking biopsies. Taking biopsies during
endoscopy can cause intra-intestinal or intramural haemorrhage, or, although
very rarely, a perforation. The risk is estimated to be < 1:10000. There is no
additional risk in sampling an extra 30 ml of blood.