Pharmacokinetics and Immune Reconstitution Following Discontinuation of Thiopurine Analogues: Implications for Drug Withdrawal Strategies

Journal of Crohn's & Colitis
Shomron Ben-HorinNoa Markovits

Abstract

Discontinuation of thiopurine analogues is common prior to live vaccines, during infection or when de-escalating therapy. Data regarding clearance of active metabolites and immune re-constitution is scant. We aimed to determine drug elimination and immune re-constitution following thiopurine cessation. The elimination kinetics of 6-thioguanine nucleotides (6-TGN) were determined in nine inflammatory bowel disease [IBD] patients discontinuing thiopurines. Immune reconstitution was evaluated by toxic shock syndrome toxin 1 [TSST1] or anti-CD3 [OKT3]-induced CD4+ T-cell proliferation, following an initial exposure to TSST1 and 6-mercaptopurine [6MP], separately or combined. All patients discontinuing thiopurines displayed first-order elimination kinetics of 6-TGN, with a median elimination half-life of 6.8 days [interquartile range 5.9-8.4]. Resting CD4+ T-cells exposed to 6MP preserved their response to subsequent polyclonal or Vβ2+-preferential stimulation. By contrast, exposure of TSST1-activated CD4+ T-cells to 6MP inhibited their subsequent Vβ2+clonal response to further stimulation [p = 0.008], whereas overall response to further non-Vβ2-selective stimulation with OKT3 was unaltered [p = 0.9]. Upon 6MP/azathioprine discontin...Continue Reading

References

Jul 15, 1995·Annals of Internal Medicine·D C PearsonL R Sutherland
Sep 1, 1995·British Journal of Clinical Pharmacology·A Rostami-HodjeganJ S Lilleyman
Oct 31, 2001·Alimentary Pharmacology & Therapeutics·O H NielsenJ Rask-Madsen
Jan 16, 2003·Pharmacological Research : the Official Journal of the Italian Pharmacological Society·Ian D R ArnottJack Satsangi
Apr 17, 2003·The Journal of Clinical Investigation·Imke TiedeMarkus F Neurath
May 8, 2003·The Journal of Immunology : Official Journal of the American Association of Immunologists·Laurence QuéméneurLaurent Genestier
Sep 3, 2003·European Journal of Biochemistry·Antonios KlokouzasStephen B Hladky
Jun 30, 2004·Clinical Gastroenterology and Hepatology : the Official Clinical Practice Journal of the American Gastroenterological Association·Stephen B HanauerPaul Rutgeerts
Jan 29, 2011·Clinical Pharmacology and Therapeutics·M V RellingUNKNOWN Clinical Pharmacogenetics Implementation Consortium
Sep 29, 2011·Gastroenterology·Edouard LouisUNKNOWN Groupe D'etudes Thérapeutiques Des Affections Inflammatoires Digestives
Jan 20, 2012·Journal of Digestive Diseases·Laurie S ConklinXuhang Li
Mar 13, 2014·Journal of Crohn's & Colitis·J F RahierUNKNOWN European Crohn's and Colitis Organisation (ECCO)
Mar 22, 2014·Inflammatory Bowel Diseases·Jason M Swoger, Miguel Regueiro
Jul 30, 2014·Clinical Gastroenterology and Hepatology : the Official Clinical Practice Journal of the American Gastroenterological Association·David DrobneGert Van Assche
Jun 3, 2015·Alimentary Pharmacology & Therapeutics·S Ben-HorinX Roblin
May 18, 2016·The Journal of Biological Chemistry·Jin-Young ShinJongyun Heo
Feb 6, 2017·Current Treatment Options in Gastroenterology·Gerassimos J Mantzaris

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Citations

Jan 11, 2020·Journal of Crohn's & Colitis·Britta Siegmund
Apr 30, 2020·Alimentary Pharmacology & Therapeutics·Aysha H Al-AniBritt Christensen
Apr 10, 2020·Gastroenterology·David T RubinUNKNOWN International Organization for the Study of Inflammatory Bowel Disease

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