Optimization of tools for monitoring, evaluating, and treating inflammatory conditions of the bowel

Crohn’s disease (CD) and ulcerative colitis (UC) are the two main types of inflammatory bowel disease (IBD). The prevalence of these conditions is approximately 0.7%. With the advent of new treatments and improved management algorithms throughout the last century, the mortality rates associated with these conditions have decreased steeply. However, IBD is still a major cause of lifetime morbidity. Immune checkpoint inhibitor-induced enterocolitis, or immune-mediated enterocolitis (IMC), is a similar yet distinct condition that may arise as a side-effect to treatment with immune checkpoint inhibitors against various types of neoplasias. The main aim of this thesis work was to generate new knowledge on how to monitor, evaluate, and treat inflammatory conditions of the bowel with a focus on IBD and IMC.

In paper I, we successfully evaluated off-label use of the anti-α4β7 integrin inhibitor vedolizumab for IMC in a cohort of patients treated with ipilimumab or nivolumab due to metastasized melanoma or lung cancer, respectively.

In paper II, we investigated the impact of a non-medical switch from the originator infliximab to its biosimilar CT-P13 in a cohort of 313 IBD patients with a follow-up period of 12 months. Our results indicated that this type of switch was feasible with maintaned therapeutic effect and no new safety signals.

In paper III, we examined the feasibility of a non-medical switch from maintenance intravenously to subcutaneously administered vedolizumab in a cohort of 89 IBD patients. Our data indicated that this type of switch could be carried out with maintained therapeutic effect, safety, improved overall patient satisfaction, at a reduced cost.

In paper IV, we developed a novel endoscopic score for assessment of UC disease acitivity based on the two inflammatory descriptors vascular pattern (scored 0-2 points) and ulcers (scored 0-3 points). The score accounts for the most severely affected segment but also the total inflammatory burden of the large bowel. The new endoscopic score is referred to as the Simple Endoscopic Score for Ulcerative Colitis (SES-UC), and has the advantages of being simple to use without compromising performance features.

Taken together, these results have contributed with new knowledge on how to manage inflammatory conditions of the bowel with a focus on IBD and IMC.