RESUMEN
BACKGROUND AND AIMS: Ustekinumab is an effective treatment for inflammatory bowel diseases. However, some patients do not respond to conventional doses. The aim of the study was to evaluate the effectiveness of intravenous maintenance Ustekinumab in patients with secondary failure. METHODS: Single-center, retrospective study in adult patients with intravenous maintenance ustekinumab. The reduction of biochemical activity markers, ustekinumab trough levels and clinical indices of activity were evaluated. Biological remission was defined as the percentage decrease fecal calprotectin ≥ 80% and/or final fecal calprotectin ≤ 250 and C reactive protein < 5mg/L. RESULTS: 31 patients were included: Crohn's disease 77.4%. All included patients were bio-exposed and 61.3% had carried ≥ 2 biologics. Pre-intravenous maintenance mean Harvey-Bradshaw Index was 6.5±4,38 vs 5±3,1 at week 8 (p=0.024) vs 4.1±3.1 at week 24 (p=0.019). The median ustekinumab trough levels pre-intravenous maintenance were 1.40µg/ml [IQR 2.3] vs 5.35µg/ml [IQR 4.1] at week 8 (p<0.001) vs 4.8µg/ml [IQR 3.9] at week 24 (p<0.001). The pre-intravenous maintenance median fecal calprotectin was 809µg/g [IQR: 2256] vs 423µg/g [IQR: 999] at week 8 (p=0.025) vs 333µg/g [508] (p=0.001) at week 24. At the end of follow-up 48% went into biological remission. The presence of perianal disease was associated with lower biological remission (70.6% vs 27.3%, p=0.025). Median intravenous ustekinumab maintenance time was 8.55 [IQR 23.9] months. In 83.9% of patients no serious infections or malignancy were documented. CONCLUSIONS: The use of maintenance intravenous ustekinumab appears to be an effective and safe strategy that can be evaluated as a salvage treatment especially in highly bioexposed patients.
RESUMEN
An impaired expression of α-defensins (α-Defs) in the ileal mucosa and, conversely, increased levels in plasma, have been reported in Crohn's disease (CD). However, the specificity and correlation of these findings with the degree of inflammation are unclear. We aimed to characterize the concentration and utility of ileal and plasma α-Defs in CD and to analyse a potential epigenetic mechanism of α-Def expression. Peripheral blood samples and ileal biopsies were obtained from patients at disease onset (aCD), from those who achieved remission (iCD) and from two control groups (healthy controls and non-CD-aetiology ileitis patients). Plasma α-Defs 1-3 and 4 were detected by enzyme-linked immunosorbent assay (ELISA); α-Def 5 by immunolocalization. Methylation analysis of the α-Def 5 gene was performed using the MassARRAY EpiTYPER system. Plasma α-Defs 1-3 concentrations were significantly higher in aCD with ileal involvement (L1, L3) versus iCD or the control groups. The α-Defs 1-3 concentrations were also similar to healthy controls in patients with non-CD ileitis. There was a significant positive correlation between plasma α-Defs 1-3 levels in aCD and the endoscopic index, as well as with C-reactive protein (CRP) levels. The immunopositivity scoring showed significantly reduced α-Def 5 expression in ileal inflamed (aCD) versus non-inflamed mucosa (iCD and healthy controls). The α-Def 5 gene showed a higher methylation status in CD patients than controls, regardless of the inflammation. Plasma α-Defs 1-3 concentrations correlate with the degree of inflammation and appear to be specific biomarkers of ileal-CD at diagnosis. Ileal α-Def 5 expression is down-regulated permanently by methylation.