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Thiopurine Metabolite Shunting in Late Pregnancy Increases the Risk of Intrahepatic Cholestasis of Pregnancy in Women With Inflammatory Bowel Disease, and Can be Managed With Split Dosing.
Prentice, Ralley; Flanagan, Emma; Wright, Emily; Prideaux, Lani; Connell, William; Sparrow, Miles; De Cruz, Peter; Lust, Mark; Hardikar, Winita; Goldberg, Rimma; Vogrin, Sara; Palmer, Kirsten; Ross, Alyson; Burns, Megan; Greeve, Tessa; Bell, Sally.
Afiliación
  • Prentice R; Monash Health, Gastroenterology Department, Melbourne, VIC, Australia.
  • Flanagan E; St Vincent's Hospital Melbourne, Gastroenterology Department, Melbourne, VIC, Australia.
  • Wright E; Faculty of Medicine, Nursing and Health Sciences, Monash University, Melbourne, VIC, Australia.
  • Prideaux L; St Vincent's Hospital Melbourne, Gastroenterology Department, Melbourne, VIC, Australia.
  • Connell W; Faculty of Medicine, Dentistry and Health Sciences, University of Melbourne, Melbourne, VIC, Australia.
  • Sparrow M; St Vincent's Hospital Melbourne, Gastroenterology Department, Melbourne, VIC, Australia.
  • De Cruz P; Faculty of Medicine, Dentistry and Health Sciences, University of Melbourne, Melbourne, VIC, Australia.
  • Lust M; Monash Health, Gastroenterology Department, Melbourne, VIC, Australia.
  • Hardikar W; St Vincent's Hospital Melbourne, Gastroenterology Department, Melbourne, VIC, Australia.
  • Goldberg R; Faculty of Medicine, Dentistry and Health Sciences, University of Melbourne, Melbourne, VIC, Australia.
  • Vogrin S; Faculty of Medicine, Nursing and Health Sciences, Monash University, Melbourne, VIC, Australia.
  • Palmer K; Alfred Health, Gastroenterology Department, Melbourne, VIC, Australia.
  • Ross A; Faculty of Medicine, Nursing and Health Sciences, Monash University, Melbourne, VIC, Australia.
  • Burns M; Austin Health, Gastroenterology Department, Melbourne, VIC, Australia.
  • Greeve T; St Vincent's Hospital Melbourne, Gastroenterology Department, Melbourne, VIC, Australia.
  • Bell S; Faculty of Medicine, Dentistry and Health Sciences, University of Melbourne, Melbourne, VIC, Australia.
J Crohns Colitis ; 18(7): 1081-1090, 2024 Aug 06.
Article en En | MEDLINE | ID: mdl-38366352
ABSTRACT
BACKGROUND AND

AIMS:

The risk of intrahepatic cholestasis of pregnancy [ICP] is increased in thiopurine-exposed pregnancies. Thiopurine 'shunting', with a 6-methylmercaptopurine [MMP] to 6-thioguanine [TGN] ratio of >11, progresses over pregnancy, and may promote ICP development. We aimed to explore the association between thiopurine exposure and ICP, including the hypothesised impact of thiopurine shunting, and identify risk minimisation strategies.

METHODS:

This prospective multicentre cohort study compared thiopurine and biologic monotherapy-exposed pregnant participants. Disease activity and obstetric outcome data, thiopurine metabolites, bile acids, and transaminases were obtained before conception, in each trimester, at delivery, and postpartum. Thiopurine dose management was at the discretion of the treating physician.

RESULTS:

Included were 131 thiopurine and 147 biologic monotherapy-exposed pregnancies. MMP/TGN ratio increased from preconception to third trimester [p <0.01], with approximately 25% of participants shunting in pregnancy. Second trimester split dosing led to a decrease in the median MMP/TGN ratio from 18 (interquartile range [IQR] 6-57) to 3 [IQR 2-3.5] at delivery [p = 0.04]. The risk of ICP was increased in thiopurine-exposed pregnancies (6.7% [7/105] vs 0% [0/112], p <0.001), with all ICP cases occurring in the setting of antenatal thiopurine shunting. Thiopurine dose increases (risk ratio [RR] 8.10, 95% confidence interval [CI] 1.88-34.85, p = 0.005) and shunting in third trimester [6.20, 1.21-30.73, p = 0.028] and at delivery [14.18, 1.62-123.9, p = 0.016] were associated with an increased risk of ICP.

CONCLUSIONS:

Thiopurine exposure is associated with an increased risk of ICP, particularly following dose increases antenatally and with shunting in late pregnancy. The latter may be effectively managed with split dosing, although further studies are warranted.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Complicaciones del Embarazo / Enfermedades Inflamatorias del Intestino / Colestasis Intrahepática / Mercaptopurina Límite: Adult / Female / Humans / Pregnancy Idioma: En Revista: J Crohns Colitis Asunto de la revista: GASTROENTEROLOGIA Año: 2024 Tipo del documento: Article País de afiliación: Australia Pais de publicación: Reino Unido
Texto completo
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XML
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Complicaciones del Embarazo / Enfermedades Inflamatorias del Intestino / Colestasis Intrahepática / Mercaptopurina Límite: Adult / Female / Humans / Pregnancy Idioma: En Revista: J Crohns Colitis Asunto de la revista: GASTROENTEROLOGIA Año: 2024 Tipo del documento: Article País de afiliación: Australia Pais de publicación: Reino Unido