Abstract
Abstract Background Early prediction of the response to biological drugs in Inflammatory Bowel Diseases (IBD) is of utmost importance to allow prompt optimization of therapeutic strategies. Ustekinumab (UST) is nowadays a milestone in the treatment of Crohn’s disease (CD), but potential markers predicting its long-term efficacy are still lacking. Multimodal ultrasound (US), encompassing B-mode US, color-Doppler and contrast-enhanced US (CEUS), is a promising non-invasive technique, providing complementary information to endoscopy, due to its ability to both assess transmural healing and quantify changes in bowel microvascularization over time. The main objective of this study was to evaluate the role of multimodal US in predicting endoscopic response to UST in patients with CD. The secondary aim was to develop an US score that allows an early detection of treatment response. Methods We conducted a prospective monocentric study in the IBD outpatient clinic of Policlinico Agostino Gemelli in Rome, enrolling consecutive patients with moderate to severe ileal CD, who were scheduled to begin UST therapy as per clinical practice. Demographic, clinical and laboratory data were collected. Clinical activity was defined according to Harvey-Bradshaw Index. A complete US evaluation including B mode, Doppler, dynamic CEUS and elastography was perfomed at the time of induction (T0) and after 8 (T1), 16 (T2), 24 (T3) and 48 (T4) weeks of therapy. Each US parameter and their variations from baseline were correlated with endoscopic response (SES-CD reduction of at least 50% from baseline) and mucosal healing (SES-CD < 3) after 1 year. Results A total of 52 patients were included, 29 (55.8%) of which reached endoscopic response at T4. Median values of US parameters at the various time points were significantly different in the group who achieved endoscopic response from non reponders’ group (Figure 1). The univariate analysis showed that the percentage changes between T3 and T0 of bowel wall thickness, Limberg score (LS), mean signal intensity, rise time, wash-in rate (WiR), C reactive protein and Harvey-Bradshaw Index were associated with long-term therapeutic outcome (table 1). At the multivariate logistic regression analysis, three independent predictors of endoscopic response were selected: male sex, ∆%LS, and ∆%WiR. Based on the above parameters, we developed an US score that showed a good performance in predicting 1 year-endoscopic response (area under the curve: 0.91). Conclusion Multimodal ultrasound provides early predictors of the long-term therapeutic outcome in patients with CD treated with UST.
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