Longitudinal monitoring of STAT3 phosphorylation and histologic outcome of tofacitinib therapy in patients with ulcerative colitis
Summary 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...
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| Veröffentlicht in: | Alimentary pharmacology & therapeutics 2022-07, Vol.56 (2), p.282-291 |
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| creator | Verstockt, Bram Volk, Valery Jaeckel, Charlot Alsoud, Dahham Sabino, João Nikolaus, Susanna Outtier, An Krönke, Nicole Feuerhake, Friedrich De Hertogh, Gert Rosenstiel, Philip Vermeire, Séverine Schreiber, Stefan Ferrante, Marc Aden, Konrad |
| description | Summary
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.
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. |
| doi_str_mv | 10.1111/apt.16955 |
| format | Article |
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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.
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.</description><identifier>ISSN: 0269-2813</identifier><identifier>EISSN: 1365-2036</identifier><identifier>DOI: 10.1111/apt.16955</identifier><identifier>PMID: 35484689</identifier><language>eng</language><publisher>England: Wiley Subscription Services, Inc</publisher><subject>Endoscopy ; Immunohistochemistry ; Inflammatory bowel disease ; Lamina propria ; Mucosa ; Patients ; Phosphorylation ; Remission ; Stat3 protein ; Tumor necrosis factor ; Ulcerative colitis</subject><ispartof>Alimentary pharmacology & therapeutics, 2022-07, Vol.56 (2), p.282-291</ispartof><rights>2022 The Authors. published by John Wiley & Sons Ltd.</rights><rights>2022 The Authors. Alimentary Pharmacology & Therapeutics published by John Wiley & Sons Ltd.</rights><rights>2022. This article is published under http://creativecommons.org/licenses/by-nc/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c3535-2bb26fe207c34ce7c722b6b216bc980212da48b9e26a6915d4f85330c5ce09a83</citedby><cites>FETCH-LOGICAL-c3535-2bb26fe207c34ce7c722b6b216bc980212da48b9e26a6915d4f85330c5ce09a83</cites><orcidid>0000-0003-2254-7771 ; 0000-0002-7351-0023 ; 0000-0003-3898-7093</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://onlinelibrary.wiley.com/doi/pdf/10.1111%2Fapt.16955$$EPDF$$P50$$Gwiley$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://onlinelibrary.wiley.com/doi/full/10.1111%2Fapt.16955$$EHTML$$P50$$Gwiley$$Hfree_for_read</linktohtml><link.rule.ids>314,776,780,1411,1427,27903,27904,45553,45554,46388,46812</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/35484689$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Verstockt, Bram</creatorcontrib><creatorcontrib>Volk, Valery</creatorcontrib><creatorcontrib>Jaeckel, Charlot</creatorcontrib><creatorcontrib>Alsoud, Dahham</creatorcontrib><creatorcontrib>Sabino, João</creatorcontrib><creatorcontrib>Nikolaus, Susanna</creatorcontrib><creatorcontrib>Outtier, An</creatorcontrib><creatorcontrib>Krönke, Nicole</creatorcontrib><creatorcontrib>Feuerhake, Friedrich</creatorcontrib><creatorcontrib>De Hertogh, Gert</creatorcontrib><creatorcontrib>Rosenstiel, Philip</creatorcontrib><creatorcontrib>Vermeire, Séverine</creatorcontrib><creatorcontrib>Schreiber, Stefan</creatorcontrib><creatorcontrib>Ferrante, Marc</creatorcontrib><creatorcontrib>Aden, Konrad</creatorcontrib><title>Longitudinal monitoring of STAT3 phosphorylation and histologic outcome of tofacitinib therapy in patients with ulcerative colitis</title><title>Alimentary pharmacology & therapeutics</title><addtitle>Aliment Pharmacol Ther</addtitle><description>Summary
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.
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.</description><subject>Endoscopy</subject><subject>Immunohistochemistry</subject><subject>Inflammatory bowel disease</subject><subject>Lamina propria</subject><subject>Mucosa</subject><subject>Patients</subject><subject>Phosphorylation</subject><subject>Remission</subject><subject>Stat3 protein</subject><subject>Tumor necrosis factor</subject><subject>Ulcerative colitis</subject><issn>0269-2813</issn><issn>1365-2036</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2022</creationdate><recordtype>article</recordtype><sourceid>24P</sourceid><sourceid>WIN</sourceid><recordid>eNp10U1PwyAABmBiNG5-HPwDhsSLHjb5KKw9LotfyRJNnOeGUrphKFSgLrv6y2VOPZhIQjjw8BJ4ATjDaIzTuBZdHGNeMLYHhphyNiKI8n0wRIQXI5JjOgBHIbwihPgEkUMwoCzLM54XQ_Axd3apY19rKwxsndXReW2X0DXweTFdUNitXEjTb4yI2lkobA1XOkRn3FJL6PooXau2PrpGSB211RWMK-VFt4Hawi6dUzYGuNZxBXsj007U7wpKZ5IOJ-CgESao0-_1GLzc3ixm96P5493DbDofScpoelNVEd4ogiaSZlJN5ISQilcE80oWOSKY1CLLq0IRLniBWZ01OaMUSSYVKkROj8HlLrfz7q1XIZatDlIZI6xyfSgJZzmh6ftQohd_6KvrffqhrUp3kQyjrbraKeldCF41Zed1K_ymxKjcFlOmYsqvYpI9_07sq1bVv_KniQSud2Ctjdr8n1ROnxa7yE8dz5lr</recordid><startdate>202207</startdate><enddate>202207</enddate><creator>Verstockt, Bram</creator><creator>Volk, Valery</creator><creator>Jaeckel, Charlot</creator><creator>Alsoud, Dahham</creator><creator>Sabino, João</creator><creator>Nikolaus, Susanna</creator><creator>Outtier, An</creator><creator>Krönke, Nicole</creator><creator>Feuerhake, Friedrich</creator><creator>De Hertogh, Gert</creator><creator>Rosenstiel, Philip</creator><creator>Vermeire, Séverine</creator><creator>Schreiber, Stefan</creator><creator>Ferrante, Marc</creator><creator>Aden, Konrad</creator><general>Wiley Subscription Services, Inc</general><scope>24P</scope><scope>WIN</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7T5</scope><scope>7TK</scope><scope>7U9</scope><scope>H94</scope><scope>M7N</scope><scope>7X8</scope><orcidid>https://orcid.org/0000-0003-2254-7771</orcidid><orcidid>https://orcid.org/0000-0002-7351-0023</orcidid><orcidid>https://orcid.org/0000-0003-3898-7093</orcidid></search><sort><creationdate>202207</creationdate><title>Longitudinal monitoring of STAT3 phosphorylation and histologic outcome of tofacitinib therapy in patients with ulcerative colitis</title><author>Verstockt, Bram ; Volk, Valery ; Jaeckel, Charlot ; Alsoud, Dahham ; Sabino, João ; Nikolaus, Susanna ; Outtier, An ; Krönke, Nicole ; Feuerhake, Friedrich ; De Hertogh, Gert ; Rosenstiel, Philip ; Vermeire, Séverine ; Schreiber, Stefan ; Ferrante, Marc ; Aden, Konrad</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c3535-2bb26fe207c34ce7c722b6b216bc980212da48b9e26a6915d4f85330c5ce09a83</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2022</creationdate><topic>Endoscopy</topic><topic>Immunohistochemistry</topic><topic>Inflammatory bowel disease</topic><topic>Lamina propria</topic><topic>Mucosa</topic><topic>Patients</topic><topic>Phosphorylation</topic><topic>Remission</topic><topic>Stat3 protein</topic><topic>Tumor necrosis factor</topic><topic>Ulcerative colitis</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Verstockt, Bram</creatorcontrib><creatorcontrib>Volk, Valery</creatorcontrib><creatorcontrib>Jaeckel, Charlot</creatorcontrib><creatorcontrib>Alsoud, Dahham</creatorcontrib><creatorcontrib>Sabino, João</creatorcontrib><creatorcontrib>Nikolaus, Susanna</creatorcontrib><creatorcontrib>Outtier, An</creatorcontrib><creatorcontrib>Krönke, Nicole</creatorcontrib><creatorcontrib>Feuerhake, Friedrich</creatorcontrib><creatorcontrib>De Hertogh, Gert</creatorcontrib><creatorcontrib>Rosenstiel, Philip</creatorcontrib><creatorcontrib>Vermeire, Séverine</creatorcontrib><creatorcontrib>Schreiber, Stefan</creatorcontrib><creatorcontrib>Ferrante, Marc</creatorcontrib><creatorcontrib>Aden, Konrad</creatorcontrib><collection>Wiley Online Library Open Access</collection><collection>Wiley Online Library Free Content</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Immunology Abstracts</collection><collection>Neurosciences Abstracts</collection><collection>Virology and AIDS Abstracts</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>Algology Mycology and Protozoology Abstracts (Microbiology C)</collection><collection>MEDLINE - Academic</collection><jtitle>Alimentary pharmacology & therapeutics</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Verstockt, Bram</au><au>Volk, Valery</au><au>Jaeckel, Charlot</au><au>Alsoud, Dahham</au><au>Sabino, João</au><au>Nikolaus, Susanna</au><au>Outtier, An</au><au>Krönke, Nicole</au><au>Feuerhake, Friedrich</au><au>De Hertogh, Gert</au><au>Rosenstiel, Philip</au><au>Vermeire, Séverine</au><au>Schreiber, Stefan</au><au>Ferrante, Marc</au><au>Aden, Konrad</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Longitudinal monitoring of STAT3 phosphorylation and histologic outcome of tofacitinib therapy in patients with ulcerative colitis</atitle><jtitle>Alimentary pharmacology & therapeutics</jtitle><addtitle>Aliment Pharmacol Ther</addtitle><date>2022-07</date><risdate>2022</risdate><volume>56</volume><issue>2</issue><spage>282</spage><epage>291</epage><pages>282-291</pages><issn>0269-2813</issn><eissn>1365-2036</eissn><abstract>Summary
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.
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.</abstract><cop>England</cop><pub>Wiley Subscription Services, Inc</pub><pmid>35484689</pmid><doi>10.1111/apt.16955</doi><tpages>10</tpages><orcidid>https://orcid.org/0000-0003-2254-7771</orcidid><orcidid>https://orcid.org/0000-0002-7351-0023</orcidid><orcidid>https://orcid.org/0000-0003-3898-7093</orcidid><oa>free_for_read</oa></addata></record> |
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| source | Wiley-Blackwell Journals; Wiley Online Library Free Content; EZB Electronic Journals Library |
| subjects | Endoscopy Immunohistochemistry Inflammatory bowel disease Lamina propria Mucosa Patients Phosphorylation Remission Stat3 protein Tumor necrosis factor Ulcerative colitis |
| title | Longitudinal monitoring of STAT3 phosphorylation and histologic outcome of tofacitinib therapy in patients with ulcerative colitis |
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