Pregnancy Outcomes in Patients Treated with Upadacitinib: Analysis of Data from Clinical Trials and Postmarketing Reports.

IF 4 2区医学 Q1 PHARMACOLOGY & PHARMACY Drug Safety Pub Date : 2024-10-01 Epub Date: 2024-07-15 DOI:10.1007/s40264-024-01454-0

Uma Mahadevan, Gweneth Levy, Lianne Gensler, Mira Ali, Ana P Lacerda, Lani Wegrzyn, Hannah Palac, Tina Bhutani-Jacques, Millie Long, Megan E B Clowse, Alexa B Kimball, Christina Chambers, Anthony R Scialli

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Abstract

Background and objective: Upadacitinib is indicated for diseases affecting persons of childbearing potential including rheumatoid arthritis, psoriatic arthritis, axial spondyloarthritis, atopic dermatitis, Crohn's disease, and ulcerative colitis; however, teratogenicity was observed in animal studies. Given the potential for human fetal risk, pregnancy avoidance measures were required during clinical trials. This analysis describes pregnancy outcomes in patients exposed to upadacitinib during pregnancy.

Methods: Clinical trial and postmarketing cases of in utero exposure to upadacitinib were identified in AbbVie's safety database through 25 April, 2023. Analysis of clinical trial cases and postmarketing reports are presented separately; prospective and retrospectively reported pregnancy outcomes are integrated for each. Descriptive rates are presented to summarize outcomes.

Results: There were 128 maternal upadacitinib-exposed pregnancies with known outcomes identified; 80 and 48 pregnancies were reported in clinical trials and the postmarketing setting, respectively. In clinical trials (mean in utero exposure of 5 weeks, 3 days), live births (54%), spontaneous abortions (24%), elective terminations (21%), and ectopic pregnancy (1%) were reported. There was one report of a congenital malformation: a 35-week infant with an atrial septal defect. In postmarketing cases, live births (46%), spontaneous abortions (38%), elective terminations (15%), and ectopic pregnancy (2%) were reported.

Conclusions: As the data are limited for in utero exposure to upadacitinib, definitive conclusions cannot be drawn regarding the effect of upadacitinib on pregnancy outcomes. Rates of adverse pregnancy outcomes with upadacitinib exposure were comparable to rates observed in the general population or patients with autoimmune inflammatory diseases. To date, no apparent evidence of teratogenicity exists in the analyses of human pregnancies exposed to upadacitinib during the first trimester.

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乌达替尼治疗患者的妊娠结局：来自临床试验和上市后报告的数据分析。

背景和目的奥帕他替尼适用于影响育龄人群的疾病，包括类风湿性关节炎、银屑病关节炎、轴性脊柱关节炎、特应性皮炎、克罗恩病和溃疡性结肠炎；然而，在动物实验中观察到了致畸性。鉴于对人类胎儿的潜在风险，临床试验期间需要采取避孕措施。本分析报告描述了妊娠期接触达达替尼的患者的妊娠结局：方法：从艾伯维的安全数据库中找到了截至 2023 年 4 月 25 日期间子宫内暴露于奥达替尼的临床试验和上市后病例。对临床试验病例和上市后报告的分析单独列出；对前瞻性和回顾性报告的妊娠结局分别进行整合。对结果进行了描述性比率总结：结果：共发现128例暴露于达帕替尼的孕产妇，并确定了已知的结果；临床试验和上市后报告的妊娠分别为80例和48例。在临床试验中（平均宫内暴露时间为 5 周 3 天），报告了活产（54%）、自然流产（24%）、选择性终止妊娠（21%）和宫外孕（1%）。有一例先天性畸形报告：一名 35 周的婴儿患有房间隔缺损。在上市后病例中，有活产（46%）、自然流产（38%）、选择性终止妊娠（15%）和宫外孕（2%）的报告：结论：由于宫内暴露于达达替尼的数据有限，因此无法就达达替尼对妊娠结局的影响得出明确结论。与普通人群或自身免疫性炎症患者相比，奥达替尼不良妊娠结局的发生率相当。迄今为止，在对妊娠头三个月暴露于达达替尼的人类妊娠进行的分析中，尚无明显的致畸证据。

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

Drug Safety 医学-毒理学

CiteScore

7.60

自引率

7.10%

发文量

112

审稿时长

6-12 weeks

期刊介绍： Drug Safety is the official journal of the International Society of Pharmacovigilance. The journal includes: Overviews of contentious or emerging issues. Comprehensive narrative reviews that provide an authoritative source of information on epidemiology, clinical features, prevention and management of adverse effects of individual drugs and drug classes. In-depth benefit-risk assessment of adverse effect and efficacy data for a drug in a defined therapeutic area. Systematic reviews (with or without meta-analyses) that collate empirical evidence to answer a specific research question, using explicit, systematic methods as outlined by the PRISMA statement. Original research articles reporting the results of well-designed studies in disciplines such as pharmacoepidemiology, pharmacovigilance, pharmacology and toxicology, and pharmacogenomics. Editorials and commentaries on topical issues. Additional digital features (including animated abstracts, video abstracts, slide decks, audio slides, instructional videos, infographics, podcasts and animations) can be published with articles; these are designed to increase the visibility, readership and educational value of the journal’s content. In addition, articles published in Drug Safety Drugs may be accompanied by plain language summaries to assist readers who have some knowledge of, but not in-depth expertise in, the area to understand important medical advances.