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Inflammatory bowel diseases (IBD), including Crohn’s disease (CD) and ulcerative colitis (UC), are chronic, relapsing–remitting conditions. The introduction of biologic therapies, especially anti-TNF agents, has greatly improved treatment. However, many patients still do not benefit sufficiently due to primary non-response, secondary loss of response, or early discontinuation for reasons such as side effects. This thesis explores how the effectiveness and long-term use of anti-TNF therapy in IBD can be optimized.

Across several clinical studies, factors influencing sustained anti-TNF treatment were evaluated. Longer treatment duration was associated with a lower risk of discontinuation, while female sex was linked to earlier withdrawal due to adverse events. The impact of stopping immunomodulators in patients successfully treated with anti-TNF combination therapy was also examined: although discontinuation increased antibody formation, it did not result in higher treatment failure rates. Switching back from biosimilar to originator infliximab was rarely required, but when indicated, it was safe and effective.

Treatment adherence proved to be another important, modifiable determinant of therapeutic success. An electronic injection device with digital reminders, however, did not improve adherence.

In a translational part of the thesis, the role of the chemokine CXCL4 in Crohn’s-related fibrosis was investigated. Increased CXCL4 gene expression was found in patients with active inflammation and fibrosis, with striking CXCL4 deposits in L cells within fibrotic and inflamed tissue samples. These findings suggest CXCL4 contributes to the pathogenesis of fibrosis in CD.

Overall, the results provide new insights into tailoring anti-TNF therapy for more effective and sustainable use, and into the mechanisms underlying fibrostenotic Crohn’s disease.