| Autor: |
Gennep, Sara van, Fung, Ivan C N, Jong, Djuna C de, Ramkisoen, Rishand K, Clasquin, Esmé, Jong, Jitteke de, Vries, Leonie C S de, Jonge, Wouter J de, Gecse, Krisztina B, Löwenberg, Mark, Woolcott, John C, Mookhoek, Aart, D'Haens, Geert R |
| Zdroj: |
Journal of Crohn's & Colitis; Aug2024, Vol. 18 Issue 8, p1283-1291, 9p |
| Abstrakt: |
Background and aims Histological outcomes and JAK-STAT signalling were assessed in a prospective ulcerative colitis [UC] patient cohort after 8 weeks treatment with tofacitinib, an oral Janus kinase [JAK] inhibitor. Methods Forty UC patients received tofacitinib 10 mg twice daily for 8 weeks. Treatment response was defined as histo-endoscopic mucosal improvement [HEMI]. Histological remission was defined as a Robarts Histopathology Index [RHI] ≤3 points and histological response as 50% decrease in RHI. Mucosal expression of JAK1-3, tyrosine kinase 2 [TYK2], and total signal transducer and activator of transcription [STAT] 1-6 were assessed using immunohistochemistry [IHC]. Results At baseline, the median RHI was 14 (interquartile range [IQR] 10–19). Of 40 [65%] patients, 26 had severe endoscopic disease [endoscopic Mayo score 3] and 31/40 [78%] failed prior anti-tumour necrosis factor [anti-TNF] treatment. At Week 8, 15 patients [38%] had HEMI, 23 patients [58%] histological remission, and 34 [85%] histological response. RHI decreased by a median of 14 points [IQR 9-21] in responders [ p <0.001] and by 6 points [IQR 0-13] in non-responders [ p = 0.002]. STAT1, STAT3, and STAT5 expression levels decreased significantly in the whole cohort. Responders had lower Week 8 STAT1 expression levels compared with non-responders [0.2%, IQR 0.1-2.8 vs 4.3%, IQR 1.2-11.9, p = 0.001], suggesting more profound STAT1 blockade. A trend of higher baseline JAK2 expression was observed in tofacitinib non-responders [2.7%, IQR 0.1-7.7] compared with responders [0.4%, IQR 0.1-2.1]. Conclusions Tofacitinib treatment resulted in histological improvement in the majority of UC patients and in a substantial decrease of STAT1, STAT3, and STAT5 expression. HEMI was associated with more profound suppression of STAT1. [ABSTRACT FROM AUTHOR] |
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