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.