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Mucosal microbiota and gene expression are associated with long-term remission after discontinuation of adalimumab in ulcerative colitis.

ABSTRACT: Given that sustained remission is the ultimate treatment goal in the management of patients with ulcerative colitis (UC), the decision to stop anti-tumor necrosis factor (anti-TNF) treatment in UC patients is difficult. The aim of this study was to evaluate mucosal microbiota and gene expression profiles associated with long-term remission after discontinuation of anti-TNF therapy. In nine UC patients who received anti-TNF therapy for 6 months, microbiota isolated from uninflamed mucosae and gene expression in inflamed and uninflamed mucosae were investigated at week 0 and at week 24. At treatment initiation, Fusobacterium sp. and Veillonella dispar were over-represented in the relapse group compared with the non-relapse group. After treatment, Dorea sp. and Lachnospira sp. were over-represented in the non-relapse group. In the relapse group only, a significant shift in gut bacterial community composition was found between week 0 and week 24. Gene expression of ALIX (PDCD6IP) and SLC9A3 was significantly higher in the non-relapse group than in the relapse group. Lastly, we used machine learning methods to identify relevant gene signatures associated with sustained remission. Statistical analyses of microbiota and expression profiles revealed differences between UC patients who did or did not keep remission after the discontinuation of TNF inhibitors.Trial registration: UMIN000020785: Evaluation of adalimumab therapy in mesalazine-resistant or -intolerant ulcerative colitis; an observational study (EARLY study).

SUBMITTER: Sakurai T

PROVIDER: S-EPMC7644643 | biostudies-literature | 2020 Nov

REPOSITORIES: biostudies-literature

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Mucosal microbiota and gene expression are associated with long-term remission after discontinuation of adalimumab in ulcerative colitis.

Sakurai Toshiharu T Nishiyama Hiroki H Sakai Kazuko K De Velasco Marco A MA Nagai Tomoyuki T Komeda Yoriaki Y Kashida Hiroshi H Okada Akiyoshi A Kawai Isao I Nishio Kazuto K Ogata Hiroyuki H Kudo Masatoshi M

Scientific reports 20201105 1

Given that sustained remission is the ultimate treatment goal in the management of patients with ulcerative colitis (UC), the decision to stop anti-tumor necrosis factor (anti-TNF) treatment in UC patients is difficult. The aim of this study was to evaluate mucosal microbiota and gene expression profiles associated with long-term remission after discontinuation of anti-TNF therapy. In nine UC patients who received anti-TNF therapy for 6 months, microbiota isolated from uninflamed mucosae and gen ...[more]

PMID: 33154436

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Project description:BackgroundThe long-term outcomes of Ulcerative colitis (UC) after discontinuation of biological therapy are largely unknown. There is also a lack of accurate and validated markers that can predict outcome after withdrawal accurately. The aims of this study were to describe the long-term outcomes in UC patients following cessation of anti-TNF therapy and explore potential biomarkers as an approach towards precision medicine.MethodsSeventy-five patients with moderate to severe UC treated to remission with anti-tumor necrosis factor (TNF) were included in the study. This is a follow-up of previously reported UC outcomes. The patients were categorized as either "Remission" or "Relapse". The "Relapse" group was divided into subgroups determined by the highest treatment level needed to obtain remission the last 3 years of observation: non-biological therapy, biological therapy or colectomy. Remission were divided in long term remission (LTR), those using immunomodulating drugs (LTR + imids) and those using only 5-amino-salicylate (5-ASA) treatment (LTR) for the past 3 years. Analyses of mucosal gene expression by real-time PCR were performed.ResultsThe median (IQR) observation time of all patients included was 121 (111-137) months. Of the 75 patients, 46 (61%) did not receive biological therapy, including 23 (31%) in LTR ± imids. Of these 23 patients, 16 (21%) were defined as LTR with a median observation time of (IQR) 95 (77-113) months. In total 14 patients (19%) underwent colectomy during the 10 years after first remission. Mucosal TNF copies/µg mRNA < 10 000 at anti-TNF discontinuation predicted long-term remission, biological free remission and lower risk of colectomy with a HR 0.36 (0.14-0.92) for long-term remission, HR 0.17 (0.04-0.78) for biological free remission and HR 0.12 (0.01-0.91) for colectomy. IL1RL1 was normalized in LTR phenotype and higher in relapsing UC.ConclusionIn this 10-year follow-up of UC of patients with moderate to severe disease, 61% of patients experience an altered phenotype to a milder disease course without need of biological therapy. Twenty-one percent of the patients were LTR without any medication except of 5-ASA. Mucosal TNF gene expression and IL1RL1- transcripts may be of clinical utility for long term prognosis in development of precision medicine in UC.

Dataset Information

Mucosal microbiota and gene expression are associated with long-term remission after discontinuation of adalimumab in ulcerative colitis.

Publications

Mucosal microbiota and gene expression are associated with long-term remission after discontinuation of adalimumab in ulcerative colitis.

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