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dc.contributor.authorGoll, Rasmus
dc.contributor.authorMoe, Øystein Kittel
dc.contributor.authorJohnsen, Kay-Martin
dc.contributor.authorMeyer, Renate Weenås
dc.contributor.authorFriestad, Joachim
dc.contributor.authorGundersen, Mona Dixon
dc.contributor.authorKileng, Hege
dc.contributor.authorJohnsen, Knut
dc.contributor.authorFlorholmen, Jon
dc.date.accessioned2022-12-27T13:02:08Z
dc.date.available2022-12-27T13:02:08Z
dc.date.issued2022-11-17
dc.description.abstractBackground and aims - Biological therapy for inflammatory bowel disease is efficient in many cases but not all. The underlying molecular mechanisms behind non-response to biological therapy in inflammatory bowel disease are poorly described. Therefore, we aimed to characterize the mucosal cytokine transcript profile in non-immunogenic, non-responder patients with adequate trough level.<p> <p>Material and methods - Patients with ulcerative colitis (UC) (n = 21) and Crohn’s disease (CD) (n = 12) with non-response to biological therapy (anti-tumor necrosis factor (TNF) or vedolizumab) were included. Reference groups were A: untreated patients with UC or CD at debut of disease who had severe 1-year outcome, B: patients with UC or CD treated to endoscopic remission with biological agents, and C: healthy normal controls. Mucosal transcripts of TNF, interleukin (IL)17 and IL23 were measured by reverse transcription real-time quantitative polymerase chain reaction. Results Of the non-responders, 2 out of 12 CD and 1 out of 21 UC patients needed surgery during follow-up. Of the remaining non-responding patients, 8 out of 10 CD and 12 out of 20 UC patients switched biologic treatment. The remaining 2 CD and 8 UC patients continued treatment with the same biological agent with the addition of steroids, immunomodulators (AZA/MTX) and /or local steroids/5ASA. Twelve (8 UC/4 CD) out of 20 IBD patients were still non-responders after changing biological therapy to either anti-TNF (2), vedolizumab (9) or ustekinumab (1).<p> <p>The transcripts of IL17, IL23 and TNF were significantly upregulated in the non-response group compared to normal controls and patients in remission. In UC, 24% of the non-responders had normal mucosal TNF transcript indicating a non-TNF mediated inflammation. No obvious differences in gene expression were observed between primary and secondary non-responders, nor between anti-TNF and vedolizumab non-responders.<p> <p>Conclusions - Mucosal transcripts of IL17 and IL23 are highly associated with non-response to biological therapy, whereas some UC patients may also have a non-TNF mediated inflammatory pathway.en_US
dc.identifier.citationGoll, Moe, Johnsen, Meyer, Friestad, Gundersen, Kileng, Johnsen, Florholmen. Pharmacodynamic mechanisms behind a refractory state in inflammatory bowel disease. BMC Gastroenterology. 2022;22(1)
dc.identifier.cristinIDFRIDAID 2089394
dc.identifier.doi10.1186/s12876-022-02559-5
dc.identifier.issn1471-230X
dc.identifier.urihttps://hdl.handle.net/10037/27929
dc.language.isoengen_US
dc.publisherBMCen_US
dc.relation.journalBMC Gastroenterology
dc.rights.holderCopyright 2022 The Author(s)en_US
dc.rights.urihttps://creativecommons.org/licenses/by/4.0en_US
dc.rightsAttribution 4.0 International (CC BY 4.0)en_US
dc.titlePharmacodynamic mechanisms behind a refractory state in inflammatory bowel diseaseen_US
dc.type.versionpublishedVersionen_US
dc.typeJournal articleen_US
dc.typeTidsskriftartikkelen_US
dc.typePeer revieweden_US


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Attribution 4.0 International (CC BY 4.0)
Except where otherwise noted, this item's license is described as Attribution 4.0 International (CC BY 4.0)