Therapeutic Advances in Gastroenterology (Aug 2023)
Evaluation of serum cytokines and acute phase proteins as possible pharmacodynamic biomarkers to monitor endoscopic remission during ustekinumab therapy in patients with Crohn’s disease
Abstract
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)-γ (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-γ, 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.