Increased Risk of Intrahepatic Cholestasis of Pregnancy in SLE Women Exposed to Azathioprine.

IF 10.9 1区医学 Q1 RHEUMATOLOGY

Arthritis & Rheumatology Pub Date : 2026-05-04 DOI:10.1002/art.70208

Reem Farhat, Maria Del Carmen Zamora-Medina, Sang-Cheol Bae, Megan R W Barber, Ann E Clarke, Paul R Fortin, Zahi Touma, Carl A Laskin, Isabelle Malhamé, Giada Sebastiani, Christine Peschken, Manuel F Ugarte-Gil, Alexandra Legge, Sasha Bernatsky, Évelyne Vinet

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引用次数: 0

Abstract

Objectives: To evaluate the risk of intrahepatic cholestasis of pregnancy (ICP) in azathioprine (AZA)-exposed versus unexposed SLE pregnancies within the multi-centre prospective Lupus in prEGnAnCY (LEGACY) cohort.

Methods: LEGACY is conducted at Systemic Lupus International Collaborating Centres in Canada, South Korea, Peru, and Mexico. Pregnant women with SLE are enrolled before 17 weeks and followed in the second (20-24 weeks) and third (30-34 weeks) trimesters, and postpartum (8-12 weeks). Since ICP occurs after 20 weeks, only pregnancies with a second-trimester visit were included. Follow-up began at that visit and continued until delivery. AZA exposure was modelled as time-varying. The primary outcome was iatrogenic delivery for ICP or spontaneous preterm birth occurring after ICP diagnosis. Multivariable Cox models with frailties adjusted for relevant covariates. At the Montreal site, thiopurine metabolites and shunting were assessed.

Results: Among 127 SLE pregnancies (46 AZA-exposed, 81 unexposed), 10 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). AZA exposure was associated with a substantially increased risk of ICP (adjusted HR 12.1, 95% CI 2.4-59.7). All ICP cases with metabolite data (4/4) showed 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.

Conclusion: We observed that AZA exposure may be strongly associated with ICP in SLE pregnancies. Second-trimester thiopurine shunting may identify women at high risk, supporting the value of metabolite monitoring.

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暴露于硫唑嘌呤的SLE妇女妊娠期肝内胆汁淤积的风险增加。

目的：在多中心前瞻性妊娠狼疮（LEGACY）队列中评估硫唑嘌呤（AZA）暴露与未暴露的SLE妊娠肝内胆汁淤积（ICP）的风险。方法：LEGACY在加拿大、韩国、秘鲁和墨西哥的系统性狼疮国际合作中心进行。患有SLE的孕妇在17周前入组，并在妊娠中期（20-24周）和妊娠晚期（30-34周）以及产后（8-12周）进行随访。由于ICP发生在20周后，因此仅包括妊娠中期就诊的妊娠。随访从那次就诊开始，一直持续到分娩。AZA暴露建模为时变模型。主要结局是ICP的医源性分娩或ICP诊断后发生的自发性早产。对相关协变量进行脆弱性调整的多变量Cox模型。在蒙特利尔站点，评估硫嘌呤代谢物和分流。结果：在127例SLE妊娠中（46例暴露于aza， 81例未暴露于aza），发生了10例ICP病例（每个病例在不同的女性中）：暴露于aza的8例（17.4%,95% CI 9.1-30.7），未暴露的2例（2.5%,95% CI 0.7-8.6）。AZA暴露与显著增加的ICP风险相关（调整后危险度12.1,95% CI 2.4-59.7）。所有有代谢物数据的ICP病例（4/4）均显示妊娠中期分流。在所有有孕中期代谢物数据的妊娠中（n=22）， 36.4% （95% CI 19.7-57.0）发生分流，50.0% （95% CI 21.5-78.5）发生ICP。结论：我们观察到AZA暴露可能与SLE妊娠的ICP密切相关。妊娠中期硫嘌呤分流可以识别高危妇女，支持代谢物监测的价值。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Arthritis & Rheumatology RHEUMATOLOGY-

CiteScore

20.90

自引率

3.00%

发文量

371

期刊介绍： Arthritis & Rheumatology is the official journal of the American College of Rheumatology and focuses on the natural history, pathophysiology, treatment, and outcome of rheumatic diseases. It is a peer-reviewed publication that aims to provide the highest quality basic and clinical research in this field. The journal covers a wide range of investigative areas and also includes review articles, editorials, and educational material for researchers and clinicians. Being recognized as a leading research journal in rheumatology, Arthritis & Rheumatology serves the global community of rheumatology investigators and clinicians.