P575 Effect of etrasimod on immune cell subsets in colonic tissue of patients with ulcerative colitis: immunophenotyping analysis of colon biopsy samples from the phase 3 ELEVATE UC 52 and ELEVATE UC 12 trials
| العنوان: | P575 Effect of etrasimod on immune cell subsets in colonic tissue of patients with ulcerative colitis: immunophenotyping analysis of colon biopsy samples from the phase 3 ELEVATE UC 52 and ELEVATE UC 12 trials |
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| المؤلفون: | B Siegmund, H K Komori, M T Abreu, S Vermeire, I Dotan, M Goetsch, C Crosby, R Ryan, J Woolcott, S Danese |
| المصدر: | Journal of Crohn's and Colitis. 17:i701-i704 |
| بيانات النشر: | Oxford University Press (OUP), 2023. |
| سنة النشر: | 2023 |
| مصطلحات موضوعية: | Gastroenterology, General Medicine |
| الوصف: | Background Etrasimod is an investigational, once-daily, oral, selective sphingosine 1-phosphate receptor 1,4,5 (S1P1,4,5) modulator in development for the treatment of moderately to severely active ulcerative colitis (UC). Etrasimod reversibly sequesters specific lymphocyte subsets in lymph nodes, reducing circulating lymphocytes and resulting in fewer immune cells available to traffic to the gastrointestinal tract. To better understand how etrasimod reduces inflammation in UC, the phase 3 ELEVATE UC 52 and ELEVATE UC 12 trials included a per protocol exploratory immunophenotyping biomarker analysis in fixed-formalin paraffin-embedded (FFPE) colon biopsies. Methods In ELEVATE UC 52 (NCT03945188) and ELEVATE UC 12 (NCT03996369), patients (16-80 years) with moderately to severely active UC were randomised 2:1 to once-daily etrasimod 2 mg or placebo (PBO). Characterization of immune cell types in colon biopsies were assessed at baseline, week 12, and week 52 (ELEVATE UC 52 only) by Epiontis ID, an epigenetic immune monitoring method. Biomarker levels for each lymphocyte subset were evaluated between responders vs nonresponders, defined by achievement of clinical efficacy criteria within each treatment group, using t-tests and nominal P values. Results Colon biopsies were collected and analysed from 276 subjects in ELEVATE UC 52 (179 etrasimod, 97 PBO) and 150 subjects in ELEVATE UC 12 (97 etrasimod, 53 PBO). Etrasimod induced significant changes from baseline (nominal P value Conclusion In this per protocol exploratory analysis of two independent phase 3 trials, etrasimod induced changes from baseline in colonic tissue T- and B-cell subsets in subjects with UC, with nominally significant reductions observed in those who met response criteria. The reduction in activated immune cells in colonic tissue in responders suggests etrasimod induces a reduction in local inflammation that could contribute to remission. These findings are the first to report changes to immune cell subsets in colonic tissue in response to a S1P receptor modulator. |
| تدمد: | 1876-4479 1873-9946 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_________::e0b29073af0d84b2c68636ddba3752df https://doi.org/10.1093/ecco-jcc/jjac190.0705 |
| حقوق: | CLOSED |
| رقم الأكسشن: | edsair.doi...........e0b29073af0d84b2c68636ddba3752df |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 18764479 18739946 |
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