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

Autor:	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., Paramsothy S; Department of Gastroenterology and Hepatology, Concord Repatriation General Hospital, Sydney, Australia; Faculty of Medicine and Health, University of Sydney, Sydney, Australia., Kariyawasam V; Department of Gastroenterology, Blacktown Hospital, Sydney, Australia; Blacktown Clinical School, Faculty of Medicine, Western Sydney University, Sydney, Australia., Paramsothy R; Department of Gastroenterology, Blacktown Hospital, Sydney, Australia., 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., 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., An YK; Department of Gastroenterology, Mater Hospital, Brisbane, Australia; Mater Research Institute, The University of Queensland, Brisbane, Australia., Begun J; Department of Gastroenterology, Mater Hospital, Brisbane, Australia; Mater Research Institute, The University of Queensland, Brisbane, Australia., Connor SJ; Department of Gastroenterology, Liverpool Hospital, Sydney, Australia; South West Sydney Clinical Campuses, UNSW Medicine & Health, UNSW, Sydney, Australia., Corte C; AW Morrow Gastroenterology Centre, Royal Prince Alfred Hospital, Sydney, Australia., Ward MG; Department of Gastroenterology, The Alfred Hospital, Melbourne, Australia., De Cruz P; Department of Gastroenterology, Austin Hospital, Melbourne, Australia; Department of Medicine, Austin Academic Centre, The University of Melbourne, Melbourne, Australia., Lan-San Fung C; Department of Anatomical Pathology, Concord Repatriation General Hospital, Sydney, Australia., Redmond D; Department of Gastroenterology and Hepatology, Concord Repatriation General Hospital, Sydney, Australia., Chan W; Department of Gastroenterology and Hepatology, Concord Repatriation General Hospital, Sydney, Australia., Mourad F; Department of Gastroenterology and Hepatology, Concord Repatriation General Hospital, Sydney, Australia., Kermeen M; Department of Gastroenterology and Hepatology, Concord Repatriation General Hospital, Sydney, Australia., Leong RW; Department of Gastroenterology and Hepatology, Concord Repatriation General Hospital, Sydney, Australia; Faculty of Medicine and Health, University of Sydney, Sydney, Australia.
Jazyk:	angličtina
Zdroj:	Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association [Clin Gastroenterol Hepatol] 2024 Nov; Vol. 22 (11), pp. 2299-2308.e5. Date of Electronic Publication: 2024 May 09.
DOI:	10.1016/j.cgh.2024.04.019
Abstrakt:	Background & Aims: The impact of thiopurine de-escalation while 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: This multicenter randomized controlled trial recruited UC patients on vedolizumab 300 mg intravenously every 8 weeks and a thiopurine. Patients in steroid-free clinical remission for ≥6 months and endoscopic remission/improvement (Mayo endoscopic subscore ≤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 >150 μg/g or increase in Mayo endoscopic subscore ≥1 from baseline), fecal calprotectin remission (<150 μg/g), C-reactive protein remission (<5 mg/L), centrally read endoscopic remission (Mayo endoscopic subscore = 0), histologic remission (Nancy index = 0), histo-endoscopic remission, and adverse events. 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 (14.7 μg/mL, interquartile rate [IQR], 12.3-18.5 μg/mL versus 15.9 μg/mL, IQR, 10.1-22.7 μg/mL, respectively, P = 0.36). The continue group had significantly higher fecal calprotectin remission (95.0%, 19/20 versus 71.4%, 30/42; P = .03), histologic remission (80.0%, 16/20 versus 48.6%, 18/37; P = .02), and histo-endoscopic remission (75.0%, 15/20 versus 32.4%, 12/37; P = .002) than the withdrawal group. Histologic activity (hazard ratio [HR], 15.5; 95% confidence interval [CI], 1.6-146.5; P = .02) and prior anti-tumor necrosis factor exposure (HR, 6.5; 95% CI, 1.3-33.8; P = .03) predicted clinical relapse after thiopurine withdrawal. Conclusions: Thiopurine withdrawal did not affect vedolizumab trough concentrations. However, it may increase fecal calprotectin, histologic, and histo-endoscopic activity. Histologic activity and prior anti-tumor necrosis factor exposure may predict disease relapse on thiopurine withdrawal for patients using vedolizumab for UC. Australian and New Zealand Trial Registry, number ACTRN12618000812291. (Crown Copyright © 2024. Published by Elsevier Inc. All rights reserved.)
Databáze:	MEDLINE
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