Effects of Thiopurine Withdrawal on Vedolizumab-Treated Patients With Ulcerative Colitis: a Randomized Controlled Trial.

combination thiopurine vedolizumab withdrawal

Journal

Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association
ISSN: 1542-7714
Titre abrégé: Clin Gastroenterol Hepatol
Pays: United States
ID NLM: 101160775

Informations de publication

Date de publication:
08 May 2024
Historique:
received: 28 12 2023
revised: 31 03 2024
accepted: 01 04 2024
medline: 11 5 2024
pubmed: 11 5 2024
entrez: 10 5 2024
Statut: aheadofprint

Résumé

The impact of thiopurine de-escalation whilst on vedolizumab versus continuing thiopurine therapy in ulcerative colitis (UC) is unclear. We aimed to determine the effect of thiopurine withdrawal for patients with UC in remission on vedolizumab. This multi-centre randomized controlled trial recruited UC patients on vedolizumab 300mg IV every 8 weeks and a thiopurine. Patients in steroid-free clinical remission for ≥6 months and endoscopic remission/improvement (Mayo endoscopic subscore[MES]≤1) were randomized 2:1 to withdraw or continue thiopurine. Primary outcome was comparing week 48 vedolizumab trough concentrations. Secondary outcomes were clinical relapse (partial Mayo score≥3 and fecal calprotectin>150μg/g or increase in MES≥1 from baseline), fecal calprotectin remission (<150μg/g), C-reactive protein remission (<5mg/L), centrally-read endoscopic remission (MES=0), histologic remission (Nancy index=0), histo-endoscopic remission and adverse events. In total, 62 patients were randomized to continue (n=20) or withdraw (n=42) thiopurine. At week 48, vedolizumab trough concentrations were not significantly different between continue and withdrawal groups (14.7μg/mL [IQR:12.3-18.5μg/mL] versus 15.9μg/mL [IQR:10.1-22.7μg/mL] respectively, P=0.36). The continue group had significantly higher fecal calprotectin remission (95.0% [19/20] versus 71.4% [30/42], P=0.03), histologic remission (80.0% [16/20] versus 48.6% [18/37], P=0.02) and histo-endoscopic remission (75.0% [15/20] versus 32.4% [12/37], P=0.002) than the withdrawal group. Histological activity (HR:15.5 [95%CI:1.6-146.5],P=0.02) and prior anti-TNF exposure (HR:6.5 [95%CI:1.3-33.8],P=0.03) predicted clinical relapse after thiopurine withdrawal. Thiopurine withdrawal did not affect vedolizumab trough concentrations. However, it may increase fecal calprotectin, histologic and histo-endoscopic activity. Histological activity and prior anti-TNF exposure may predict disease relapse upon thiopurine withdrawal for patients using vedolizumab for UC; Australian and New Zealand Trial Registry, number ACTRN12618000812291.

Sections du résumé

BACKGROUND AND AIMS OBJECTIVE
The impact of thiopurine de-escalation whilst on vedolizumab versus continuing thiopurine therapy in ulcerative colitis (UC) is unclear. We aimed to determine the effect of thiopurine withdrawal for patients with UC in remission on vedolizumab.
METHODS METHODS
This multi-centre randomized controlled trial recruited UC patients on vedolizumab 300mg IV every 8 weeks and a thiopurine. Patients in steroid-free clinical remission for ≥6 months and endoscopic remission/improvement (Mayo endoscopic subscore[MES]≤1) were randomized 2:1 to withdraw or continue thiopurine. Primary outcome was comparing week 48 vedolizumab trough concentrations. Secondary outcomes were clinical relapse (partial Mayo score≥3 and fecal calprotectin>150μg/g or increase in MES≥1 from baseline), fecal calprotectin remission (<150μg/g), C-reactive protein remission (<5mg/L), centrally-read endoscopic remission (MES=0), histologic remission (Nancy index=0), histo-endoscopic remission and adverse events.
RESULTS RESULTS
In total, 62 patients were randomized to continue (n=20) or withdraw (n=42) thiopurine. At week 48, vedolizumab trough concentrations were not significantly different between continue and withdrawal groups (14.7μg/mL [IQR:12.3-18.5μg/mL] versus 15.9μg/mL [IQR:10.1-22.7μg/mL] respectively, P=0.36). The continue group had significantly higher fecal calprotectin remission (95.0% [19/20] versus 71.4% [30/42], P=0.03), histologic remission (80.0% [16/20] versus 48.6% [18/37], P=0.02) and histo-endoscopic remission (75.0% [15/20] versus 32.4% [12/37], P=0.002) than the withdrawal group. Histological activity (HR:15.5 [95%CI:1.6-146.5],P=0.02) and prior anti-TNF exposure (HR:6.5 [95%CI:1.3-33.8],P=0.03) predicted clinical relapse after thiopurine withdrawal.
CONCLUSION CONCLUSIONS
Thiopurine withdrawal did not affect vedolizumab trough concentrations. However, it may increase fecal calprotectin, histologic and histo-endoscopic activity. Histological activity and prior anti-TNF exposure may predict disease relapse upon thiopurine withdrawal for patients using vedolizumab for UC; Australian and New Zealand Trial Registry, number ACTRN12618000812291.

Identifiants

DOI: 10.1016/j.cgh.2024.04.019 PMID: 38729400
pubmed: 38729400
pii: S1542-3565(24)00426-9
doi: 10.1016/j.cgh.2024.04.019
pii:
doi:

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

IM

Informations de copyright

Copyright © 2024. Published by Elsevier Inc.

Auteurs

Aviv Pudipeddi (A)

Department of Gastroenterology and Hepatology, Concord Repatriation General Hospital, Sydney, Australia; Faculty of Medicine and Health, University of Sydney, Sydney, Australia. Electronic address: avivpudipeddi@gmail.com.

Sudarshan Paramsothy (S)

Department of Gastroenterology and Hepatology, Concord Repatriation General Hospital, Sydney, Australia; Faculty of Medicine and Health, University of Sydney, Sydney, Australia.

Viraj Kariyawasam (V)

Department of Gastroenterology, Blacktown Hospital, Sydney, Australia; Blacktown Clinical School, Faculty of Medicine, Western Sydney University, Sydney, Australia.

Ramesh Paramsothy (R)

Department of Gastroenterology, Blacktown Hospital, Sydney, Australia.

Simon Ghaly (S)

Department of Gastroenterology and Hepatology, St Vincent's Hospital, Sydney, Australia; School of Clinical Medicine, St Vincent's Healthcare Campus, UNSW, Sydney, Australia.

Craig Haifer (C)

Department of Gastroenterology and Hepatology, St Vincent's Hospital, Sydney, Australia; School of Clinical Medicine, St Vincent's Healthcare Campus, UNSW, Sydney, Australia.

Yoon-Kyo An (YK)

Department of Gastroenterology, Mater Hospital, Brisbane, Australia; Mater Research Institute, The University of Queensland, Brisbane, Australia.

Jakob Begun (J)

Department of Gastroenterology, Mater Hospital, Brisbane, Australia; Mater Research Institute, The University of Queensland, Brisbane, Australia.

Susan J Connor (SJ)

Department of Gastroenterology, Liverpool Hospital, Sydney, Australia; South West Sydney Clinical Campuses, UNSW Medicine & Health, UNSW, Sydney, Australia.

Crispin Corte (C)

AW Morrow Gastroenterology Centre, Royal Prince Alfred Hospital, Sydney, Australia.

Mark G Ward (MG)

Department of Gastroenterology, The Alfred Hospital, Melbourne, Australia.

Peter De Cruz (P)

Department of Gastroenterology, Austin Hospital, Melbourne, Australia; Department of Medicine, Austin Academic Centre, The University of Melbourne, Melbourne, Australia.

Caroline Lan-San Fung (CL)

Department of Anatomical Pathology, Concord Repatriation General Hospital, Sydney, Australia.

Diane Redmond (D)

Department of Gastroenterology and Hepatology, Concord Repatriation General Hospital, Sydney, Australia.

Webber Chan (W)

Department of Gastroenterology and Hepatology, Concord Repatriation General Hospital, Sydney, Australia.

Fadi Mourad (F)

Department of Gastroenterology and Hepatology, Concord Repatriation General Hospital, Sydney, Australia.

Melissa Kermeen (M)

Department of Gastroenterology and Hepatology, Concord Repatriation General Hospital, Sydney, Australia.

Rupert W Leong (RW)

Department of Gastroenterology and Hepatology, Concord Repatriation General Hospital, Sydney, Australia; Faculty of Medicine and Health, University of Sydney, Sydney, Australia.

Classifications MeSH