dc.contributor.author | Goll, Rasmus | |
dc.contributor.author | Moe, Øystein Kittel | |
dc.contributor.author | Johnsen, Kay-Martin | |
dc.contributor.author | Meyer, Renate Weenås | |
dc.contributor.author | Friestad, Joachim | |
dc.contributor.author | Gundersen, Mona Dixon | |
dc.contributor.author | Kileng, Hege | |
dc.contributor.author | Johnsen, Knut | |
dc.contributor.author | Florholmen, Jon | |
dc.date.accessioned | 2022-12-27T13:02:08Z | |
dc.date.available | 2022-12-27T13:02:08Z | |
dc.date.issued | 2022-11-17 | |
dc.description.abstract | Background 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.citation | Goll, 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.cristinID | FRIDAID 2089394 | |
dc.identifier.doi | 10.1186/s12876-022-02559-5 | |
dc.identifier.issn | 1471-230X | |
dc.identifier.uri | https://hdl.handle.net/10037/27929 | |
dc.language.iso | eng | en_US |
dc.publisher | BMC | en_US |
dc.relation.journal | BMC Gastroenterology | |
dc.rights.holder | Copyright 2022 The Author(s) | en_US |
dc.rights.uri | https://creativecommons.org/licenses/by/4.0 | en_US |
dc.rights | Attribution 4.0 International (CC BY 4.0) | en_US |
dc.title | Pharmacodynamic mechanisms behind a refractory state in inflammatory bowel disease | en_US |
dc.type.version | publishedVersion | en_US |
dc.type | Journal article | en_US |
dc.type | Tidsskriftartikkel | en_US |
dc.type | Peer reviewed | en_US |