Objective:

To evaluate the risk of intrahepatic cholestasis of pregnancy (ICP) in pregnancies affected by systemic lupus erythematosus (SLE) and treated with azathioprine (AZA), and to assess thiopurine metabolite profiles in these cases.

Approach:

• Study Design: A multicenter prospective cohort study within the Lupus in Pregnancy (LEGACY) cohort, involving consecutive pregnant women with SLE from multiple countries.
• Data Collection: Standardized forms collected demographic, obstetrical, comorbidity, SLE characteristics, and adverse pregnancy outcomes data at various trimesters.
• Outcome Measures: Primary outcome was iatrogenic delivery for ICP or spontaneous preterm delivery after ICP diagnosis. Thiopurine metabolites were measured in AZA-exposed patients.
• Statistical Analysis: Cox proportional hazards models were used to estimate hazard ratios for ICP associated with AZA exposure, adjusting for relevant covariates.

Key Findings:

• Pregnancies exposed to AZA showed an increased risk of ICP compared to unexposed pregnancies.
• Thiopurine metabolite profiles indicated shunting in some AZA-exposed ICP cases.
• Maternal and fetal outcomes varied based on AZA exposure in ICP cases.

Interpretation:

The study indicates a potential link between AZA exposure and increased ICP risk in SLE pregnancies.

Limitations:

• Potential exposure and outcome misclassifications.
• Lack of data on race, ethnicity, thiopurine dose, and disease activity measures.
• Limited number of events for robust statistical analysis.

Conclusion:

Further prospective studies are needed to clarify the relationship between AZA exposure and ICP in SLE pregnancies.