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

Aviv Pudipeddi; Sudarshan Paramsothy; Viraj Kariyawasam; Ramesh Paramsothy; Simon Ghaly; Craig Haifer; Yoon-Kyo An; Jakob Begun; Susan J Connor; Crispin Corte; Mark G Ward; Peter De Cruz; Caroline Lan-San Fung; Diane Redmond; Webber Chan; Fadi Mourad; Melissa Kermeen; Rupert W Leong

doi:10.1016/j.cgh.2024.04.019

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

Clin Gastroenterol Hepatol. 2024 May 8:S1542-3565(24)00426-9. doi: 10.1016/j.cgh.2024.04.019. Online ahead of print.

Authors

Aviv Pudipeddi¹, Sudarshan Paramsothy², Viraj Kariyawasam³, Ramesh Paramsothy⁴, Simon Ghaly⁵, Craig Haifer⁵, Yoon-Kyo An⁶, Jakob Begun⁶, Susan J Connor⁷, Crispin Corte⁸, Mark G Ward⁹, Peter De Cruz¹⁰, Caroline Lan-San Fung¹¹, Diane Redmond¹², Webber Chan¹², Fadi Mourad¹², Melissa Kermeen¹², Rupert W Leong²

Affiliations

¹ 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.
² Department of Gastroenterology and Hepatology, Concord Repatriation General Hospital, Sydney, Australia; Faculty of Medicine and Health, University of Sydney, Sydney, Australia.
³ Department of Gastroenterology, Blacktown Hospital, Sydney, Australia; Blacktown Clinical School, Faculty of Medicine, Western Sydney University, Sydney, Australia.
⁴ Department of Gastroenterology, Blacktown Hospital, Sydney, Australia.
⁵ Department of Gastroenterology and Hepatology, St Vincent's Hospital, Sydney, Australia; School of Clinical Medicine, St Vincent's Healthcare Campus, UNSW, Sydney, Australia.
⁶ Department of Gastroenterology, Mater Hospital, Brisbane, Australia; Mater Research Institute, The University of Queensland, Brisbane, Australia.
⁷ Department of Gastroenterology, Liverpool Hospital, Sydney, Australia; South West Sydney Clinical Campuses, UNSW Medicine & Health, UNSW, Sydney, Australia.
⁸ AW Morrow Gastroenterology Centre, Royal Prince Alfred Hospital, Sydney, Australia.
⁹ Department of Gastroenterology, The Alfred Hospital, Melbourne, Australia.
¹⁰ Department of Gastroenterology, Austin Hospital, Melbourne, Australia; Department of Medicine, Austin Academic Centre, The University of Melbourne, Melbourne, Australia.
¹¹ Department of Anatomical Pathology, Concord Repatriation General Hospital, Sydney, Australia.
¹² Department of Gastroenterology and Hepatology, Concord Repatriation General Hospital, Sydney, Australia.

PMID: 38729400
DOI: 10.1016/j.cgh.2024.04.019

Abstract

Background and aims: 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: 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: 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: 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.

Keywords: combination; thiopurine; vedolizumab; withdrawal.