Interpretation (in light of other evidence):
The primary analysis of the PITCHES trial concluded that the routine use of UDCA in women with ICP should be reconsidered; in previously reported planned subgroup analyses evaluating the primary outcome (stillbirth, preterm delivery or neonatal unit admission) and its components, there was no significant interaction of highest baseline bile acid concentration (<40 μmol/L, ≥40 μmol/L), gestational age at randomisation (<34 weeks’ gestation, ≥34 weeks’ gestation), or pregnancy (singleton, twin).6The secondary analysis presented here identified no subgroup of women in whom a reduction in bile acid concentration or itch score in response to treatment with UDCA was found. This result is in contrast with a previous, smaller, study by Glantz et al.9 that showed a reduction in maternal pruritus and bile acid concentration in a subgroup of women with bile acid concentrations ≥40 μmol/L after treatment with UDCA; however, the analysis was limited by its small size (12 women treated with UDCA vs 11 women treated with placebo) and by its duration (maximum treatment time 3 weeks).9In contrast, this study included 116 women with baseline bile acid concentrations ≥40 μmol/L and an average treatment duration of over 4 weeks. The limited correlation between serum bile acid concentrations and severity of pruritus is consistent with other studies demonstrating that the likely pruritogens in ICP are progesterone sulphates and lysophosphatidic acid.10,11
Reductions in mean bile acid concentrations were seen in all groups over the first few visits, regardless of whether the women were on active treatment or placebo. Previous clinical experience of this disease would have been confounded by almost universal treatment with UDCA, and the natural history of the disease may thus not be well understood. In particular, stratifying women by their initial bile acid trajectory demonstrated that a considerable proportion of women experienced a transient hypercholanaemia during pregnancy which resolved rapidly. This may represent a different pathology, e.g. secondary to a transient viral infection or exposure to a drug, from those with sustained hypercholanaemia in whom a diagnosis of ICP is more likely. In light of this, clinicians should take a detailed history and consider repeating bile acid measurements at subsequent visits to determine whether any elevation in bile acid concentration during pregnancy is persistent.
The repeat survey of women and clinicians found a high degree of concordance with the previous survey findings (2011),8but some variability in the size of the itch reduction that was considered sufficient to justify taking a drug. The majority of women would only consider taking a drug if it yielded a reduction in itch severity of 30 mm, but a small proportion of women (9.6%) considered taking a drug for a reduction in itch score of only 5 mm. This variability may in part reflect different interpretations of what a given distance on the visual analogue scale represents.