{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,15]],"date-time":"2026-05-15T06:08:15Z","timestamp":1778825295890,"version":"3.51.4"},"reference-count":15,"publisher":"Wiley","license":[{"start":{"date-parts":[[2026,5,14]],"date-time":"2026-05-14T00:00:00Z","timestamp":1778716800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"},{"start":{"date-parts":[[2026,5,14]],"date-time":"2026-05-14T00:00:00Z","timestamp":1778716800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100000024","name":"Canadian Institutes of Health Research","doi-asserted-by":"publisher","award":["PJT 183654"],"award-info":[{"award-number":["PJT 183654"]}],"id":[{"id":"10.13039\/501100000024","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["acrjournals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Arthritis &amp; Rheumatology"],"abstract":"<jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>To evaluate the risk of intrahepatic cholestasis of pregnancy (ICP) in azathioprine (AZA)\u2013exposed versus unexposed systemic lupus erythematosus (SLE) pregnancies within the multicenter prospective Lupus in Pregnancy (LEGACY) cohort.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>LEGACY is conducted at Systemic Lupus International Collaborating Clinics in Canada, South Korea, Peru, and Mexico. Pregnant women with SLE are enrolled before 17 weeks and followed in the second (20\u201324 weeks) and third (30\u201334 weeks) trimesters and postpartum (8\u201312 weeks). Because ICP occurs after 20 weeks, only pregnancies with a second\u2010trimester visit were included. Follow\u2010up began at that visit and continued until delivery. AZA exposure was modeled 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.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>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% confidence interval [CI] 9.1\u201330.7) and 2 among unexposed (2.5%, 95% CI 0.7\u20138.6). AZA exposure was associated with a substantially increased risk of ICP (adjusted hazard ratio 12.1, 95% CI 2.4\u201359.7). All ICP cases with metabolite data (4 of 4) showed second\u2010trimester shunting. Among all pregnancies with second\u2010trimester metabolite data (n\u00a0=\u00a022), 36.4% (95% CI 19.7\u201357.0) were shunting, and 50.0% (95% CI 21.5\u201378.5) of these developed ICP.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>We observed that AZA exposure may be strongly associated with ICP in SLE pregnancies. Second\u2010trimester thiopurine shunting may identify women at high risk, supporting the value of metabolite monitoring.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/art.70208","type":"journal-article","created":{"date-parts":[[2026,5,4]],"date-time":"2026-05-04T13:44:26Z","timestamp":1777902266000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Increased Risk of Intrahepatic Cholestasis of Pregnancy in Women With Systemic Lupus Erythematosus Exposed to Azathioprine"],"prefix":"10.1002","author":[{"ORCID":"https:\/\/orcid.org\/0009-0008-4471-1687","authenticated-orcid":false,"given":"Reem","family":"Farhat","sequence":"first","affiliation":[{"name":"Centre for Outcomes Research and Evaluation, Research Institute of the McGill University Health Centre  Montreal Quebec Canada"},{"name":"Department of Medicine, Division of Rheumatology McGill University Health Centre  Montreal Quebec Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Maria del Carmen","family":"Zamora\u2010Medina","sequence":"additional","affiliation":[{"name":"Department of Critical Care Medicine, Division of Rheumatology Instituto Nacional de Perinatologia Isidro Espinosa De Los Reyes  Mexico City Mexico"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4658-1093","authenticated-orcid":false,"given":"Sang\u2010Cheol","family":"Bae","sequence":"additional","affiliation":[{"name":"Department of Rheumatology, Hanyang University Hospital for Rheumatic Diseases Hanyang University Institute for Rheumatology Research and Hanyang Institute of Bioscience and Biotechnology  Seoul Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1055-1335","authenticated-orcid":false,"given":"Megan R. W.","family":"Barber","sequence":"additional","affiliation":[{"name":"Division of Rheumatology, Cumming School of Medicine University of Calgary  Calgary Alberta Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3112-9646","authenticated-orcid":false,"given":"Ann E.","family":"Clarke","sequence":"additional","affiliation":[{"name":"Division of Rheumatology, Cumming School of Medicine University of Calgary  Calgary Alberta Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7278-2596","authenticated-orcid":false,"given":"Paul R.","family":"Fortin","sequence":"additional","affiliation":[{"name":"Centre ARThrite, CHU de Qu\u00e9bec Universit\u00e9 Laval  Quebec City Quebec Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5177-2076","authenticated-orcid":false,"given":"Zahi","family":"Touma","sequence":"additional","affiliation":[{"name":"University of Toronto  Toronto Ontario Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9036-6326","authenticated-orcid":false,"given":"Carl A.","family":"Laskin","sequence":"additional","affiliation":[{"name":"University of Toronto  Toronto Ontario Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Isabelle","family":"Malham\u00e9","sequence":"additional","affiliation":[{"name":"Centre for Outcomes Research and Evaluation, Research Institute of the McGill University Health Centre  Montreal Quebec Canada"},{"name":"Department of Medicine, Division of General Internal Medicine McGill University Health Centre  Montreal Quebec Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Giada","family":"Sebastiani","sequence":"additional","affiliation":[{"name":"Centre for Outcomes Research and Evaluation, Research Institute of the McGill University Health Centre  Montreal Quebec Canada"},{"name":"Department of Medicine, Division of Gastroenterology McGill University Health Centre  Montreal Quebec Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Christine","family":"Peschken","sequence":"additional","affiliation":[{"name":"Rady Faculty of Health Sciences University of Manitoba  Winnipeg Manitoba Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1728-1999","authenticated-orcid":false,"given":"Manuel F.","family":"Ugarte\u2010Gil","sequence":"additional","affiliation":[{"name":"Grupo Peruano de Estudio de Enfermedades Autoinmunes Sist\u00e9micas Universidad Cient\u00edfica del Sur  Lima Peru"},{"name":"Rheumatology Department Hospital Guillermo Almenara Irigoyen  EsSalud Lima Peru"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0373-4985","authenticated-orcid":false,"given":"Alexandra","family":"Legge","sequence":"additional","affiliation":[{"name":"Division of Rheumatology, Department of Medicine Dalhousie University and Queen Elizabeth II Health Sciences Centre  Halifax Nova Scotia Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9515-2802","authenticated-orcid":false,"given":"Sasha","family":"Bernatsky","sequence":"additional","affiliation":[{"name":"Centre for Outcomes Research and Evaluation, Research Institute of the McGill University Health Centre  Montreal Quebec Canada"},{"name":"Department of Medicine, Division of Rheumatology McGill University Health Centre  Montreal Quebec Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7727-5879","authenticated-orcid":false,"given":"\u00c9velyne","family":"Vinet","sequence":"additional","affiliation":[{"name":"Centre for Outcomes Research and Evaluation, Research Institute of the McGill University Health Centre  Montreal Quebec Canada"},{"name":"Department of Medicine, Division of Rheumatology McGill University Health Centre  Montreal Quebec Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2026,5,14]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1097\/CLD.0000000000000119"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10067-017-3554-4"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1440-1746.2005.03832.x"},{"key":"e_1_2_7_5_1","doi-asserted-by":"publisher","DOI":"10.1111\/apt.70096"},{"key":"e_1_2_7_6_1","unstructured":"U.S. Food and Drug Administration.FDA alerts health care professionals of pregnancy problems associated with thiopurines. 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