| Autor: |
Oh Kyu Yoon, Adrian Serone, Robert Petryka, Chantal Tasset, Severine Vermeire, Xavier Roblin, Jason Goh, Shiva Zaboli, Xavier Hébuterne, Maria Kłopocka, Jens Brodbeck, Ethan Grant, Rene Galien, Walter Reinisch |
| Rok vydání: |
2021 |
| Předmět: |
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| Zdroj: |
Posters. |
| Popis: |
Introduction Filgotinib (FIL) is a JAK1 inhibitor under phase 3 clinical evaluation for treatment of IBD. We conducted a post hoc analysis in patients (pts) with moderately to severely active Crohn’s disease (CD) to assess the effect of FIL on markers of JAK1 signaling (STAT1/3 phosphorylation [pSTAT1/3]) within intestinal mucosa and their correlation to histologic/endoscopic indices (NCT02048618). Methods Baseline (BL) and Week 10 (W10) biopsies were collected from predefined bowel segments. Within-subject matched biopsies (FIL, n=42; placebo [PBO], n=18) were scored for histologic and endoscopic disease activity. Machine learning (Visiopharmv.2019.06) was used to quantify%pSTAT1 and%pSTAT3 positive nuclei within epithelium (Ep) and non-Ep regions. Basal pSTAT levels from 182 non-diseased segments were used to classify segments as low or high molecular disease activity (MDA). Agreement between endoscopy/histology and MDA was evaluated by Cohen’s kappa coefficient (κ) and% agreement. Results In segments with BL GHAS activity subscore ≥2, Ep (10–30%) and non-Ep (25–35%) MDA were elevated and correlated to histologic activity. Table 1 shows the effect of FIL on MDA in the intestinal mucosa: significantly fewer low BL MDA segments showed MDA worsening, and significantly more high BL MDA segments showed MDA improvement (pSTAT3 only) with FIL vs. PBO. Agreement for MDA and endoscopy was fair to moderate (κ 0.3–0.5), and for MDA and histology was moderate to good (κ 0.4–0.8). Conclusions FIL improved JAK1-related MDA within the mucosa of pts with CD. Agreement between MDA and clinical indices was highest with histology. |
| Databáze: |
OpenAIRE |
| Externí odkaz: |
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