Inflammatory bowel disease is a chronic inflammatory disorder of the gastrointestinal tract that includes Crohn’s disease and ulcerative colitis. Treatment follows a stepwise approach, with biological therapies such as tumor necrosis factor- α inhibitors, integrin inhibitors, and interleukin inhibitors currently serving as the cornerstone of therapy. Despite their effectiveness, some patients experience adverse effects or an insufficient therapeutic response, highlighting the need for reliable biological markers to predict treatment efficacy and safety.
The aim of this master’s thesis was to evaluate the impact of biological therapy on the occurrence of extraintestinal manifestations and the development of new autoantibodies, as well as to identify potential biomarkers associated with treatment response. A total of 34 patients were included in the study, 31 were treated with biological agents (infliximab, adalimumab, vedolizumab, and ustekinumab) and 3 were treated with Janus kinase inhibitors inhibitors, who serving as controls. Patients were managed at the Department of Gastroenterology, University Medical Centre Ljubljana, while laboratory analyses were performed at the Department of Rheumatology, Immunology Laboratory, University Medical Centre Ljubljana. Extraintestinal symptoms were assessed using questionnaires. Serum levels of rheumatoid factor, anti-cyclic citrullinated peptide antibodies, antibodies against extractable nuclear antigen, and antinuclear antibodies, concentrations of biological drugs at multiple time points, and levels of cytokines and chemokines before treatment and after two months were measured. Treatment response was defined using clinical indices and laboratory parameters, including C-reactive protein and fecal calprotectin.
No statistically significant differences were observed in the incidence of extraintestinal manifestations or new autoantibodies, although musculoskeletal symptoms were reported. In patients treated with ustekinumab, higher drug concentrations were associated with a better therapeutic response, while such associations were not confirmed for vedolizumab or TNF-α inhibitors. Among the analyzed inflammatory mediators, selected cytokines and chemokines showed significant changes, with IL-33 demonstrating potential predictive value for treatment response. Additional cytokines and chemokines also showed potential as predictive biomarkers. Further studies with larger patient cohorts are required to validate these findings and enable generalization to a broader population.
The findings represent a step toward a better understanding of treatment response in patients with inflammmatory bowel disease.
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