LBA:01:25 Increased risk of intrahepatic cholestasis of pregnancy in SLE women exposed to azathioprine

Objectives Intrahepatic cholestasis of pregnancy (ICP) is linked to adverse maternal and fetal outcomes. Emerging evidence from IBD cohorts and a 2024 FDA safety report suggests a strong association between thiopurines and ICP, which is concerning as azathioprine (AZA) is the immunosuppressive of choice in SLE pregnancies. However, data in SLE are scarce. Thus, we performed a multi-centre prospective cohort study to evaluate the risk of ICP in AZA-exposed versus unexposed SLE pregnancies.Methods The Lupus in prEGnAnCY cohort enrols SLE pregnancies 20 weeks) were included, with follow-up continuing until delivery. AZA exposure was modelled as time-varying, and the primary outcome was iatrogenic delivery for ICP or spontaneous preterm birth occurring after ICP diagnosis. Cox proportional hazards models with frailties adjusted for maternal demographics, co-morbidities, disease activity, and glucocorticoid use. At the Montreal site, thiopurine metabolites were measured at each visit, with shunting defined using established cut-offs.Results Of 127 SLE pregnancies, 46 were AZA-exposed and 81 unexposed ( table 1). Ten ICP cases occurred (each in a distinct woman): 8 among AZA-exposed (17.4%, 95%CI 9.1-30.7) and 2 among unexposed (2.5%, 95%CI 0.7-8.6). Nine of ten ICP cases underwent an iatrogenic delivery and one AZA-exposed case experienced a spontaneous preterm delivery. AZA exposure was associated with a substantially increased risk of ICP (unadjusted HR 9.1, 95%CI 1.9-44.5; adjusted HR 11.9, 95%CI 2.2-65.1). All ICP cases with metabolite data (4/4) exhibited second-trimester shunting. Among all pregnancies with second-trimester metabolite data (n=22), 36.4% (95%CI 19.7-57.0) were shunting, and 50.0% (95%CI 21.5-78.5) of these developed ICP. All ICP pregnancies resulted in live births, although AZA-exposed cases tended to have higher bile acid levels, earlier delivery, and lower birth weight for gestational age versus unexposed cases.Abstract LBA:01:25 Table 1Characteristics of SLE pregnancies at the second-trimester visit according to azathioprine (AZA) exposure (n=127)Conclusions SLE pregnancies exposed to AZA had a substantially higher risk of ICP than unexposed pregnancies. Second-trimester thiopurine shunting appears to strongly predict ICP, highlighting the need for metabolite monitoring and vigilance when prescribing AZA in SLE pregnancies.