No role of Ursodeoxycholic acid in Intrahepatic cholestasis of pregnancy finds Lancet study
UK: Intrahepatic cholestasis of pregnancy is a common liver disorder that occurs during pregnancy. The condition, if left untreated, can lead to stillbirth and preterm birth. Ursodeoxycholic acid is widely used for its treatment without an adequate evidence base.
A recent study published in The Lancet journal has found the treatment (ursodeoxycholic acid) to be ineffective. In the study, ursodeoxycholic acid did not reduce adverse perinatal outcomes in women with intrahepatic cholestasis of pregnancy. Thus, the authors stress that routine use of the treatment for the condition should be reconsidered.
Intrahepatic cholestasis of pregnancy is characterized by maternal pruritus and increased serum bile acid concentrations impairing liver function. Bile build-up causes increased rates of stillbirth, preterm birth, and neonatal unit admission.
Lucy C Chappell, School of Life Course Sciences, King's College London, London, UK, and colleagues set out to determine whether ursodeoxycholic acid reduces adverse perinatal outcomes in women with intrahepatic cholestasis of pregnancy.
The PITCHES trial was conducted across 33 hospital maternity units in England and Wales between December 2015 and September 2018. The researchers recruited 605 pregnant women with intrahepatic cholestasis of pregnancy (ICP). Half of them received ursodeoxycholic acid (known as 'urso') and half received a placebo. Blood tests and samples were collected, measured the women's level of itching and recorded birth information.
The primary outcome was a composite of perinatal death (in-utero fetal death after randomization or known neonatal death up to 7 days after birth), preterm delivery (<37 weeks' gestation), or neonatal unit admission for at least 4 h (from birth until hospital discharge).
Key findings of the study include:
- The primary outcome analysis included 304 women and 322 infants in the ursodeoxycholic acid group, and 300 women and 318 infants in the placebo group (consent to use data was withdrawn for 1 woman and 2 infants).
- The primary composite outcome occurred in 74 (23%) of 322 infants in the ursodeoxycholic acid group and 85 (27%) of 318 infants in the placebo group (adjusted risk ratio 0·85 [95% CI 0·62–1·15]).
- Urso did not have an impact on pregnancy outcomes including preterm birth, neonatal unit admission, and stillbirth.
- It did not show any meaningful improvement in itch for most women, nor did it reduce the woman's bile acid levels.
Scientists are now looking to identify other potential treatments for women with ICP. A clinical drug trial will be starting in early 2020 using rifampicin, an antibiotic that is also an effective treatment for itch outside pregnancy and improves removal of bile acids from the bloodstream.
"It is now clear that urso should not be used routinely to treat all women with ICP. Our future research focus will be to try to establish whether there is a subgroup of women who may still benefit from this drug, and also to focus on new drugs to improve outcomes for mothers and babies of ICP pregnancies," added Professor Catherine Williamson, Department of Women & Children's Health at King's College London and co-investigator of the PITCHES trial.
To read the complete study follow the link: https://doi.org/10.1016/S0140-6736(19)31270-X