Article ; Online: Longitudinal monitoring of STAT3 phosphorylation and histologic outcome of tofacitinib therapy in patients with ulcerative colitis.
Alimentary pharmacology & therapeutics
2022 Volume 56, Issue 2, Page(s) 282–291
Abstract: Background: Tofacitinib is the first in class, pan-JAK inhibitor approved for ulcerative colitis (UC). Clinical efficacy has been shown, but long-term real-life endoscopic and histologic data are lacking.: Aim: To investigate the effects of ... ...
| Abstract | Background: Tofacitinib is the first in class, pan-JAK inhibitor approved for ulcerative colitis (UC). Clinical efficacy has been shown, but long-term real-life endoscopic and histologic data are lacking. Aim: To investigate the effects of tofacitinib in patients with refractory UC focussing on endoscopic, histologic and molecular outcomes, including STAT3 phosphorylation (pSTAT3) detection in the spatial context of mucosal inflammation METHODS: We prospectively monitored 59 highly refractory patients (96.7% anti-TNF exposure, 91.7% vedolizumab exposure) initiating tofacitinib at two IBD referral centres and assessed outcome at the end of induction and after 48 weeks of therapy. Endoscopic improvement was defined as a Mayo endoscopic subscore ≤1, endoscopic and histologic remission as Mayo endoscopic subscore 0 and Nancy histologic score 0. Multiplex immunohistochemistry with multispectral imaging was used to assess pSTAT3. Results: Endoscopic improvement was achieved by 24.4% and 30.5% of patients at weeks 8 and 48, respectively. Endoscopic and histologic remission rates were 11.1%, 23.7 and 16.7%, 21.4%, respectively. Endoscopic improvement at week 8 was significantly associated with treatment continuation in the long-term (72.7% vs 20.6%, p = 0.003). Although we observed a gradual decrease of mucosal pSTAT3 levels in both remitters and non-remitters (p < 0.05), no association with treatment outcome could be demonstrated. However, lamina propria pSTAT3 was significantly associated with the Nancy Histologic index (p = 0.004). Conclusion: Tofacitinib can induce and maintain endoscopic and histologic remission in up to one-quarter of highly refractory UC patients. Longitudinal monitoring of nuclear pSTAT3 in mucosal tissue compartments reflects distinctive on-target effects, independently of long-term treatment outcomes. |
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| MeSH term(s) | Colitis, Ulcerative/diagnosis ; Colitis, Ulcerative/drug therapy ; Humans ; Janus Kinase Inhibitors/therapeutic use ; Phosphorylation ; Piperidines/therapeutic use ; Pyrimidines/therapeutic use ; Remission Induction ; STAT3 Transcription Factor/metabolism ; Treatment Outcome |
| Chemical Substances | Janus Kinase Inhibitors ; Piperidines ; Pyrimidines ; STAT3 Transcription Factor ; STAT3 protein, human ; tofacitinib (87LA6FU830) |
| Language | English |
| Publishing date | 2022-04-28 |
| Publishing country | England |
| Document type | Journal Article ; Research Support, Non-U.S. Gov't |
| ZDB-ID | 639012-2 |
| ISSN | 1365-2036 ; 0269-2813 ; 0953-0673 |
| ISSN (online) | 1365-2036 |
| ISSN | 0269-2813 ; 0953-0673 |
| DOI | 10.1111/apt.16955 |
| Database | MEDical Literature Analysis and Retrieval System OnLINE |
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