Ursodeoxycholic Acid Ineffective for Liver Disorder of Pregnancy

By Reuters Staff

August 10, 2019

NEW YORK (Reuters Health) - Ursodeoxycholic acid, the currently recommended treatment for intrahepatic cholestasis of pregnancy (ICP), does not reduce adverse perinatal outcomes and its routine use "should be reconsidered," conclude investigators in the PITCHES randomized controlled trial.

ICP causes a build-up of bile acids in the blood, and symptoms include itching, which is often severe. ICP is associated with increased rates of stillbirth, preterm birth and admission to the neonatal unit.

"Ursodeoxycholic acid is widely used as a treatment without an adequate evidence base," the authors note in The Lancet, online August 1. The PITCHES study shows that this drug is "not the answer," lead author Dr. Lucy Chappell of King's College London said in a statement.

PITCHES was a double-blind, multicenter, randomized placebo-controlled trial conducted at 33 hospital maternity units in England and Wales. A total of 605 women with ICP received ursodeoxycholic acid (500 mg twice daily) or placebo.

The dose could be increased in increments of one tablet a day every three to 14 days if there was no biochemical or symptomatic improvement, to a maximum of four tablets per day (equivalent to 2 g ursodeoxycholic acid per day) or reduced one tablet a day (equivalent to 500 mg ursodeoxycholic acid a day) at clinicians' discretion.

The primary outcome was a composite of perinatal death (in-utero fetal death after randomization or known neonatal death up to seven days after birth), preterm delivery (<37 weeks' gestation), or neonatal unit admission for at least four hours (from birth until discharge). 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.

Ursodeoxycholic acid did not have an impact on the primary outcome, which 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% confidence interval, 0.62 to 1.15).

There was also no discernible effect of ursodeoxycholic acid on the primary perinatal composite outcome, its components, or key maternal outcomes in a subgroup of women identified by higher peak bile-acid-concentration baseline.

"A biologically plausible and clinically important reduction is unlikely to have been missed," the authors note.

Ursodeoxycholic acid also did not show any meaningful improvement in itch for most women, nor did it reduce the woman's bile acid levels, they report.

There were two serious adverse events in the ursodeoxycholic acid group and six in the placebo group. None were thought to be related to treatment.

In a statement, Jenny Chambers, CEO of ICP Support said, "As a charity we witness the anxiety that many women with ICP experience because the fear of stillbirth is uppermost in their minds; effective drug treatments are therefore vital to help reduce this fear. The trial clearly demonstrates that for most women urso is not the drug to do this and while the outcome is likely to be hugely disappointing for women, it is also vital that they are not being falsely reassured."

"What we now urgently need," she added, "is a drug treatment that can reduce both the itch and the risk of stillbirth that is associated with the condition and ICP Support will continue to work with researchers in their fight to do this."

The study was funded by the National Institute for Health Research Efficacy and Mechanism Evaluation Program. The authors have no relevant disclosures.

SOURCE: http://bit.ly/2YGhRT4

Lancet 2019.