{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,30]],"date-time":"2026-10-30T23:13:11Z","timestamp":1793401991014,"version":"4.5.0"},"reference-count":23,"publisher":"BMJ","issue":"1","license":[{"start":{"date-parts":[[2024,1,4]],"date-time":"2024-01-04T00:00:00Z","timestamp":1704326400000},"content-version":"unspecified","delay-in-days":3,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"name":"Duke Health Enable","award":["N\/A"],"award-info":[{"award-number":["N\/A"]}]},{"DOI":"10.13039\/100006260","name":"Rheumatology Research Foundation","doi-asserted-by":"publisher","award":["Scientist Development Award"],"award-info":[{"award-number":["Scientist Development Award"]}],"id":[{"id":"10.13039\/100006260","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100005627","name":"Thrasher Research Fund","doi-asserted-by":"publisher","award":["14486"],"award-info":[{"award-number":["14486"]}],"id":[{"id":"10.13039\/100005627","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["bmj.com"],"crossmark-restriction":true},"short-container-title":["Lupus Sci Med"],"accepted":{"date-parts":[[2023,12,14]]},"published-print":{"date-parts":[[2024,1]]},"abstract":"<jats:sec>\n                  <jats:title>Objective<\/jats:title>\n                  <jats:p>Despite widespread use of azathioprine (AZA) during pregnancy, no studies evaluated the impact of pregnancy on AZA metabolites 6-thioguanine nucleotide (6-TGN) and 6-methylmercaptopurine nucleotide (6-MMPN) disposition in rheumatic diseases. This study characterises changes in AZA metabolite concentrations throughout pregnancy in women with rheumatic disease and explores relationships between metabolite concentrations, maternal disease activity, and neonatal outcomes.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>Patients with rheumatic disease from a single centre prescribed AZA prior to pregnancy and \u22651 blood sample during pregnancy (5\/2016 to 4\/2022) were included. Commercial laboratories quantified AZA metabolite concentrations. The upper safety limit for 6-MMPN was &gt;5700\u2009pmol\/8\u00d710<jats:sup>8<\/jats:sup> RBC. The therapeutic target for 6-TGN was \u2265159\u2009pmol\/8\u00d710<jats:sup>8<\/jats:sup> RBC. Repeated correlation measures were used to evaluate the relationship between metabolite concentrations and pregnancy duration, and the relationship between 6-TGN concentration and SLE Physician Global Assessment (PGA). The relationship between pregnancy average 6-TGN and neonatal gestational age at birth was analysed using linear regression.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>Thirty-seven pregnancies in 35\u2009women with 108 serum samples were included. There was no significant difference in dose-adjusted 6-TGN concentrations across pregnancy and peripartum, whereas 6-MMPN concentrations appeared higher during pregnancy. No elevated transaminases or cholestasis were observed concurrently with 6-MMPN above 5700\u2009pmol\/8\u00d710<jats:sup>8<\/jats:sup> RBC. Metabolite concentrations were related to total AZA dosage, weight-based dosage and TPMT phenotype. In pregnant women with SLE achieving average 6-TGN in the therapeutic range, we observed a non-significant reduction in PGA and increase in neonatal gestational age at birth.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusions<\/jats:title>\n                  <jats:p>In this exploratory study, we did not observe systematic changes in 6-TGN concentrations throughout pregnancy and peripartum, whereas 6-MMPN concentrations were higher during pregnancy. Monitoring AZA metabolite concentrations in pregnancy is a potential tool to identify medication non-adherence as well as patients with high 6-MMPN in whom dosage adjustment or close laboratory monitoring may optimise safety.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1136\/lupus-2023-001036","type":"journal-article","created":{"date-parts":[[2024,1,10]],"date-time":"2024-01-10T00:23:46Z","timestamp":1704846226000},"page":"e001036","update-policy":"https:\/\/doi.org\/10.1136\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":12,"title":["Azathioprine metabolite levels and outcomes during pregnancies with rheumatic disease"],"prefix":"10.1136","volume":"11","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4016-1680","authenticated-orcid":false,"given":"Stephen","family":"Balevic","sequence":"first","affiliation":[{"name":"Duke Clinical Research Institute, Durham, North Carolina, USA"},{"name":"Department of Medicine, Duke University, Durham, North Carolina, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Catherine A","family":"Sims","sequence":"additional","affiliation":[{"name":"Department of Medicine, Duke University, Durham, North Carolina, USA"},{"name":"Durham Veterans Affairs Hospital, Durham, North Carolina, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3107-5545","authenticated-orcid":false,"given":"Amanda","family":"Eudy","sequence":"additional","affiliation":[{"name":"Department of Medicine, Duke University, Durham, North Carolina, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Valerie","family":"Smith","sequence":"additional","affiliation":[{"name":"Durham Veterans Affairs Hospital, Durham, North Carolina, USA"},{"name":"Department of Population Health Sciences, Duke University, Durham, North Carolina, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8579-3470","authenticated-orcid":false,"given":"Megan","family":"Clowse","sequence":"additional","affiliation":[{"name":"Department of Medicine, Duke University, Durham, North Carolina, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"239","published-online":{"date-parts":[[2024,1,3]]},"reference":[{"key":"2025091511365376000_11.1.e001036.1","doi-asserted-by":"publisher","DOI":"10.1016\/j.rdc.2007.01.002"},{"key":"2025091511365376000_11.1.e001036.2","doi-asserted-by":"publisher","DOI":"10.1136\/annrheumdis-2015-208840"},{"key":"2025091511365376000_11.1.e001036.3","doi-asserted-by":"crossref","first-page":"529","DOI":"10.1002\/art.41191","article-title":"2020 American college of rheumatology guideline for the management of reproductive health in rheumatic and musculoskeletal diseases","volume":"72","author":"Sammaritano","year":"2020","journal-title":"Arthritis Rheumatol"},{"key":"2025091511365376000_11.1.e001036.4","doi-asserted-by":"crossref","first-page":"10","DOI":"10.1186\/s13075-021-02699-1","article-title":"Preterm birth is strongly affected by the glucocorticoid dose during pregnancy in women complicated by systemic lupus erythematosus","volume":"24","author":"Shimada","year":"2022","journal-title":"Arthritis Res Ther"},{"key":"2025091511365376000_11.1.e001036.5","doi-asserted-by":"publisher","DOI":"10.3899\/jrheum.070968"},{"key":"2025091511365376000_11.1.e001036.6","unstructured":"Product information. azathioprine tablets. Ahmnedabad India Amneal Pharmaceuticals LLC; 2022."},{"key":"2025091511365376000_11.1.e001036.7","doi-asserted-by":"publisher","DOI":"10.3748\/wjg.v17.i37.4166"},{"key":"2025091511365376000_11.1.e001036.8","doi-asserted-by":"publisher","DOI":"10.1111\/j.1572-0241.2006.00538.x"},{"key":"2025091511365376000_11.1.e001036.9","doi-asserted-by":"crossref","first-page":"810","DOI":"10.1111\/apt.16294","article-title":"Maternal thiopurine metabolism during pregnancy in inflammatory bowel disease and clearance of thiopurine metabolites and outcomes in exposed neonates","volume":"53","author":"Flanagan","year":"2021","journal-title":"Aliment Pharmacol Ther"},{"key":"2025091511365376000_11.1.e001036.10","doi-asserted-by":"publisher","DOI":"10.1146\/annurev-pharmtox-011613-140009"},{"key":"2025091511365376000_11.1.e001036.11","doi-asserted-by":"publisher","DOI":"10.2165\/11597440-000000000-00000"},{"key":"2025091511365376000_11.1.e001036.12","doi-asserted-by":"publisher","DOI":"10.1002\/art.22156"},{"key":"2025091511365376000_11.1.e001036.13","doi-asserted-by":"publisher","DOI":"10.1007\/s10787-015-0239-y"},{"key":"2025091511365376000_11.1.e001036.14","doi-asserted-by":"publisher","DOI":"10.1136\/gutjnl-2012-303615"},{"key":"2025091511365376000_11.1.e001036.15","doi-asserted-by":"publisher","DOI":"10.1191\/096120399680411272"},{"key":"2025091511365376000_11.1.e001036.16","doi-asserted-by":"publisher","DOI":"10.1002\/art.1780340802"},{"key":"2025091511365376000_11.1.e001036.17","unstructured":"American College of Obstetricians and Gynecologists . How your fetus grows during pregnancy. Available: https:\/\/www.acog.org\/womens-health\/faqs\/how-your-fetus-grows-during-pregnancy [Accessed 10 Oct 2023]."},{"key":"2025091511365376000_11.1.e001036.18","doi-asserted-by":"crossref","first-page":"374","DOI":"10.1002\/cpt.1194","article-title":"A prospective international study on adherence to treatment in 305 patients with flaring SLE: assessment by drug levels and self-administered questionnaires","volume":"106","author":"Costedoat-Chalumeau","year":"2019","journal-title":"Clin Pharmacol Ther"},{"key":"2025091511365376000_11.1.e001036.19","doi-asserted-by":"publisher","DOI":"10.1002\/art.22898"},{"key":"2025091511365376000_11.1.e001036.20","doi-asserted-by":"publisher","DOI":"10.3389\/fpsyg.2017.00456"},{"key":"2025091511365376000_11.1.e001036.21","doi-asserted-by":"publisher","DOI":"10.1097\/01.ftd.0000179839.71138.6d"},{"key":"2025091511365376000_11.1.e001036.22","doi-asserted-by":"crossref","unstructured":"Balevic SJ , Weiner D , Clowse MEB , et al . Hydroxychloroquine PK and exposure-response in pregnancies with lupus: the importance of adherence for neonatal outcomes. Lupus Sci Med 2022;9. doi:10.1136\/lupus-2021-000602","DOI":"10.1136\/lupus-2021-000602"},{"key":"2025091511365376000_11.1.e001036.23","doi-asserted-by":"crossref","unstructured":"Lambert-Fliszar F , Bernatsky S , Kalache F , et al . Personalised therapy during preconception and gestation in SLE: usefulness of 6-mercaptopurine metabolite levelswith azathioprine. Lupus Sci Med 2021;8. doi:10.1136\/lupus-2021-000519","DOI":"10.1136\/lupus-2021-000519"}],"container-title":["Lupus Science &amp; Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/syndication.highwire.org\/content\/doi\/10.1136\/lupus-2023-001036","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,9,15]],"date-time":"2025-09-15T18:36:57Z","timestamp":1757961417000},"score":1,"resource":{"primary":{"URL":"https:\/\/lupus.bmj.com\/lookup\/doi\/10.1136\/lupus-2023-001036"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,1]]},"references-count":23,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2024,1,3]]},"published-print":{"date-parts":[[2024,1]]}},"alternative-id":["10.1136\/lupus-2023-001036"],"URL":"https:\/\/doi.org\/10.1136\/lupus-2023-001036","relation":{},"ISSN":["2053-8790"],"issn-type":[{"value":"2053-8790","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,1]]}}}