Integrase inhibitor drugs during pregnancy and congenital anomalies: A case/non-case study from the global pharmacovigilance database VigiBase®.

IF 2.9 4区 医学 Q2 PHARMACOLOGY & PHARMACY
Laura Saint-Lary, Isabelle Lacroix, Valériane Leroy, Agnès Sommet
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引用次数: 0

Abstract

In 2018, a significant neural tube defects (NTD) signal was reported after pre-conceptional exposure to dolutegravir, but was not confirmed in further analysis. Since 2019, dolutegravir-based regimen, an integrase inhibitor (INI), is recommended by WHO as the most-effective first-line therapy in all patients living with HIV. To explore the potential INI-related teratogenic effect, we searched disproportionate signals between exposure to INI-class drugs and congenital anomalies, compared to non-INI drugs, using the international pharmacovigilance database, VigiBase®. We selected all the reports registered in VigiBase® between 01/01/2007 and 30/03/2021 on any antiretroviral drug-related fetal or neonatal adverse drug reactions, declared either in children (<2 years) exposed in utero or in pregnant women (12-50 years). A case/non-case study was conducted to detected signals between congenital anomalies and prenatal exposure to any INI-class drug, compared to non-INI drugs, by estimating adjusted reporting odds ratios (aROR) with 95% confidence intervals (95%CI). We identified 2521 unique reports, among which 664 (26.3%) were related to INI-class use. Overall, 520 congenital anomalies were cited from 327 unique reports, of whom 31.0% were INI-related. Compared to non-INI drugs, no significant disproportionate reporting signal between prenatal exposure to INI-class drugs and congenital anomalies was found (aROR 1.13; 95% CI:0.85-1.51). However, specific significant signals were reported for raltegravir/elvitegravir/dolutegravir drug exposure and urinary malformations (aROR 2.43; 95%CI:1.08-5.43), digestive malformations (aROR 3.09; 95%CI:1.22-7.84), and NTDs (aROR 3.02; 95%CI:1.09-8.37). Although specific congenital anomalies signals associated with raltegravir/elvitegravir/dolutegravir exposure were notified, causal relationship needs to be further investigated in prospective studies.

孕期服用整合酶抑制剂药物与先天性畸形:来自全球药物警戒数据库 VigiBase® 的病例/非病例研究。
2018 年,有报告称受孕前暴露于多鲁特韦后出现了明显的神经管缺陷(NTD)信号,但未在进一步分析中得到证实。自2019年起,世界卫生组织推荐将基于多鲁曲韦的方案(一种整合酶抑制剂(INI))作为所有HIV感染者最有效的一线疗法。为了探索与 INI 相关的潜在致畸效应,我们使用国际药物警戒数据库 VigiBase® 搜索了与非 INI 类药物相比,INI 类药物暴露与先天性畸形之间不成比例的信号。我们选取了 VigiBase® 中登记的 2007 年 1 月 1 日至 2021 年 3 月 30 日期间所有与抗逆转录病毒药物相关的胎儿或新生儿药物不良反应报告,这些报告要么是在儿童中公布的,要么是在新生儿中公布的。
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来源期刊
Pharmacology Research & Perspectives
Pharmacology Research & Perspectives Pharmacology, Toxicology and Pharmaceutics-General Pharmacology, Toxicology and Pharmaceutics
CiteScore
5.30
自引率
3.80%
发文量
120
审稿时长
20 weeks
期刊介绍: PR&P is jointly published by the American Society for Pharmacology and Experimental Therapeutics (ASPET), the British Pharmacological Society (BPS), and Wiley. PR&P is a bi-monthly open access journal that publishes a range of article types, including: target validation (preclinical papers that show a hypothesis is incorrect or papers on drugs that have failed in early clinical development); drug discovery reviews (strategy, hypotheses, and data resulting in a successful therapeutic drug); frontiers in translational medicine (drug and target validation for an unmet therapeutic need); pharmacological hypotheses (reviews that are oriented to inform a novel hypothesis); and replication studies (work that refutes key findings [failed replication] and work that validates key findings). PR&P publishes papers submitted directly to the journal and those referred from the journals of ASPET and the BPS
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