期刊
THERAPEUTIC ADVANCES IN GASTROENTEROLOGY
卷 16, 期 -, 页码 -出版社
SAGE PUBLICATIONS LTD
DOI: 10.1177/17562848231189110
关键词
acute phase proteins; Crohn's disease; cytokines; endoscopic remission; pharmacodynamic biomarkers; ustekinumab
This study investigated the dynamics of serum biomarker concentrations during ustekinumab treatment in Crohn's disease (CD) patients. The results showed that lower concentrations of serum amyloid A protein (SAA), interleukin-6 (IL-6), serum albumin (AGP), interferon-γ (IFN-γ), lipopolysaccharide binding protein (LBP), and interleukin-22 (IL-22) were associated with better endoscopic remission. Therefore, monitoring the concentrations of these biomarkers may be helpful for evaluating the response to ustekinumab treatment in CD patients.
Background: Since not all Crohn's disease (CD) patients respond adequately to ustekinumab therapy, biomarkers could aid to monitor treatment response and optimize therapeutic outcomes.Objectives: To explore the dynamics of serum biomarker concentrations to monitor the response to ustekinumab treatment in CD patients.Design: Retrospective, exploratory study to evaluate concentrations of serum cytokines and acute phase proteins and their relation to endoscopic remission in CD patients during ustekinumab treatment.Methods: Serum concentrations of 16 proteins including cytokines and acute phase proteins were measured using the Mesoscale Discovery Platform in serum of healthy controls (n = 13), and CD patients (n = 61) at baseline (week 0), week 8 and week 24 during ustekinumab treatment. Endoscopic remission was defined as simple endoscopic score for CD (SES-CD) <3 after 6 months of therapy.Results: Absolute concentrations of serum amyloid A protein (SAA; week 8), IL-6 (week 24), AGP (weeks 8 and 24), interferon (IFN)-? (weeks 8 and 24), lipopolysaccharide binding protein (LBP; weeks 8 and 24) and IL-22 (weeks 8 and 24) were significantly lower in endoscopic remitters compared to non-responders (p-values ranging between <0.001 and <0.05). SAA (week 8) and AGP (week 24) were the biomarkers with the highest area under the ROC curve (AUROC; 0.761 and 0.760, respectively) for identifying patients in endoscopic remission, though their performance was not superior to C-reactive protein (CRP) or faecal calprotectin. AUROCs of the predictive probability of biomarker combinations showed superiority in discriminating endoscopic remitters from non-responders in comparison to single biomarker measurements, but not as compared to faecal calprotectin.Conclusion: Although not superior to faecal calprotectin, measurement of AGP, SAA, LBF, IFN-?, IL-6 and IL-22 concentrations, and combinations thereof with or without CRP and faecal calprotectin, during ustekinumab therapy might contribute to adequate monitoring of treatment response in CD patients.
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