#4-60E. Uncovering Cholestasis Risk: Azathioprine in Lupus Pregnancies (Arthritis Rheumatol, 2026)

Have you ever encountered unexpected hepatic dysfunction in a pregnant patient with systemic lupus erythematosus (SLE) on azathioprine therapy? This prospective multicenter cohort study investigates the risk of intrahepatic cholestasis of pregnancy (ICP) among SLE pregnancies exposed to azathioprine compared to those unexposed. Evaluating 127 SLE pregnancies, researchers found that azathioprine exposure substantially increases the risk of ICP, demonstrating an adjusted hazard ratio of 12.1. The most critical finding reveals that second-trimester thiopurine shunting—where metabolism shifts toward hepatotoxic 6-methylmercaptopurine—serves as a powerful predictor for developing ICP. While these insights are compelling, clinicians must critically appraise the study's limitations, notably the modest number of overall ICP events and the highly limited sample size within the metabolite analysis subgroup, which warrant larger validation studies. For listening physicians, this underscores a vital clinical shift: rather than avoiding this crucial immunosuppressant, incorporating routine thiopurine metabolite monitoring during the second trimester could be key. Early identification of shunting allows for proactive surveillance and prompt management of ICP, ultimately mitigating the risks of preterm birth and improving both maternal and fetal outcomes in complex lupus pregnancies.

Citation: Farhat R, Vinet E, et al. Increased Risk of Intrahepatic Cholestasis of Pregnancy in Women With Systemic Lupus Erythematosus Exposed to Azathioprine. Arthritis & Rheumatology. 2026. DOI: 10.1002/art.70208

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