Disputas - Cand. med. Kay-Martin Johnsen

Avhandlingen er tilgjengelig her! / The doctoral thesis is available here!

Auditoriet er åpent for publikum. Disputasen strømmes og et opptak vil være tilgjengelig i et døgn.
The auditorium is open to the public. The defense will still be streamed, and a recording of the disputation will be available for 24 hours.

Prøveforelesning over oppgitt emne starter kl. 09.15 / The trial lecture starts at 09.15
Tittel/Title:  «Ekstraintestinale manifestasjoner ved inflammatorisk tarmsykdom»
Prøveforelesningen strømmes her / The trial lecture will be streamed here

Disputasen starter kl. 11.15 / The defense starts at 11.15
Disputasen strømmes her / The defense will be streamed here

Populærvitenskapelig sammendrag av avhandlingen/ Summary of the thesis

Ulcerative colitis (UC) is a chronic inflammation of the colon that causes symptoms such as abdominal pain, bloody stools, and diarrhea. Understanding the causes of UC, an inflammatory bowel disease (IBD), is challenging and involves a complex interplay of factors such as immune system issues, exposure to microbes, and genetic influences.

A breakthrough in UC treatment came with targeted therapies like anti-tumor necrosis factor (anti-TNF) medications. This treatment has significantly improved the management of intestinal inflammation. Personalized medicine, tailoring treatment based on biomarkers to predict disease progression, would be beneficial in assessing how treatment should be customized for each patient.

In the early stages of the disease, a gradual escalation of treatment is typically followed to gain control over inflammation. Due to the risk of overtreating, the most effective treatment is not initiated immediately and then tapered down. This, in turn, may lead to some patients experiencing prolonged periods of high inflammation and worsening of the disease before treatment escalation. The lack of tools to select suitable patients is a challenge.

Current guidelines often favor indefinite maintenance treatment due to the absence of criteria to discontinue anti-TNF treatment. The lack of biomarkers and limited knowledge of how therapy alters the course of the disease contribute to this challenge.

The high cost of IBD treatment is a significant challenge for healthcare and a burden for patients in terms of frequent hospital visits and side effects. Introducing treatment algorithms with biomarkers that can help choose the right time to discontinue expensive targeted therapy can make such treatments more accessible and reduce side effects. Similarly, biomarkers would be beneficial if they could predict which patients will need anti-TNF treatment, enabling the initiation of the most effective treatment followed by tapering. Early control of inflammation will likely improve prognoses.

By performing a colonoscopy, which involves the use of a flexible tube equipped with a camera, it is possible to obtain tissue samples from the colon and assess the expression levels of signaling molecules critical to the inflammatory process. A key molecule in this context is tumor necrosis factor (TNF). The research presented in this thesis includes measurements of TNF and other signaling molecules within the intestinal lining. Additionally, the progression of the disease in patients has been monitored over an extended period. This longitudinal observation aims to explore ways to optimize treatment strategies, identify biomarkers that can predict disease course, and enhance our understanding of the course of the disease of UC.

The thesis concludes that early and intensive treatment, especially with infliximab, can contribute to achieving rapid disease control. Long-term results suggest a shift toward a milder disease course, possibly with the normalization of TNF expression in the intestinal lining as a key marker. Discontinuation of anti-TNF treatment is feasible for most, and for those experiencing relapses, re-treatment with the same medication is effective. Biomarkers, especially mucosal TNF expression combined with histological assessment, can help identify patients suitable for early initiation of targeted treatment.

Veiledere/ Supervisors:
Hovedveileder/Main supervisor:
Førsteamanuensis Rasmus Goll, Institutt for klinisk medisin, Det helsevitenskapelige fakultet, UiT Norges arktiske universitet.

Biveileder/supervisor:
Professor Jon Florholmen, Institutt for klinisk medisin, Det helsevitenskapelige fakultet, UiT Norges arktiske universitet.

Bedømmelseskomité/Defensecomitee:
Professor emeritus Bjørn Moum, Universitetet i Oslo – 1. opponent.
Førsteamanuensis Jacob Wium Bjerrum, København Universitet – 2. opponent.
Førsteamanuensis Erin Mathiesen Hald, Institutt for klinisk medisin, Det helsevitenskapelige fakultet, UiT Norges arktiske universitet – leder av komité.

Disputasleder/ Leader of defense:
Professor Jorunn Cavanagh, Institutt for klinisk medisin, Det helsevitenskapelige fakultet, UiT Norges arktiske universitet.