Dataset Information

Fetal and Neonatal Adverse Drug Reactions Associated with Biologics Taken During Pregnancy by Women with Autoimmune Diseases: Insights from an Analysis of the World Health Organization Pharmacovigilance Database (VigiBase^®).

ABSTRACT:

Introduction

Published data on the safety of biologics other than tumor necrosis factor (TNF) inhibitors during pregnancy are limited.

Objective

The aim was to detect pharmacovigilance signals for fetal and neonatal adverse drug reactions (ADRs) to biologics taken by pregnant women with autoimmune diseases.

Methods

We performed a disproportionality analysis of the World Health Organization's VigiBase^® pharmacovigilance database from 1968 to June 1, 2021. Data were collected in June 2021. By using terms for different hierarchical levels of the Medical Dictionary for Regulatory Activities, we selected the following fetal or neonatal ADRs: stillbirth, premature birth, low birth weight, small for gestational age, and congenital malformations. The frequency of all identified ADRs for biologics of interest (adalimumab, infliximab, golimumab, certolizumab, etanercept, anakinra, canakinumab, tocilizumab, sarilumab, ustekinumab, guselkumab, secukinumab, ixekizumab, belimumab, abatacept, and rituximab) was compared with that of all other reports for all other drugs and quoted as the reporting odds ratio (ROR) [95% confidence interval]. Reports with known concomitant use of teratogenic drugs were excluded from the main analysis. Other analyses included ROR stratifications by therapeutic indication in the periods 1968-2021 and 2001-2021, and an analysis after excluding reports with steroids.

Results

In the main analysis, the RORs were particularly high for musculoskeletal malformations with anakinra (7.18 [3.50-14.73]), canakinumab (19.54 [12.82-29.79]), and abatacept (5.09 [2.77-9.33]), and for immune system disorders with canakinumab (347.88 [217.9-555.50]) and rituximab (9.27 [2.95-29.15]). After the exclusion of reports with steroids, the ROR was significant for neonatal infections with belimumab (28.49 [5.75-141.25]).

Conclusion

We identified possible associations with some adverse fetal and neonatal outcomes, suggesting that vigilance is required when prescribing certain biologics during pregnancy.

SUBMITTER: Dernoncourt A

PROVIDER: S-EPMC9676840 | biostudies-literature | 2022 Nov

REPOSITORIES: biostudies-literature

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Publications

Fetal and Neonatal Adverse Drug Reactions Associated with Biologics Taken During Pregnancy by Women with Autoimmune Diseases: Insights from an Analysis of the World Health Organization Pharmacovigilance Database (VigiBase<sup>®</sup>).

Dernoncourt Amandine A Liabeuf Sophie S Bennis Youssef Y Masmoudi Kamel K Bodeau Sandra S Laville Solène S Hurtel-Lemaire Anne-Sophie AS Gras-Champel Valérie V Batteux Benjamin B

BioDrugs : clinical immunotherapeutics, biopharmaceuticals and gene therapy 20221119 1

<h4>Introduction</h4>Published data on the safety of biologics other than tumor necrosis factor (TNF) inhibitors during pregnancy are limited.<h4>Objective</h4>The aim was to detect pharmacovigilance signals for fetal and neonatal adverse drug reactions (ADRs) to biologics taken by pregnant women with autoimmune diseases.<h4>Methods</h4>We performed a disproportionality analysis of the World Health Organization's VigiBase<sup>®</sup> pharmacovigilance database from 1968 to June 1, 2021. Data wer ...[more]

PMID: 36401769

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Project description:Introduction: Clozapine is primarily reserved for treatment-resistant schizophrenia due to safety concerns associated with its use. Infections have been reported with clozapine, which may lead to elevated serum levels of the drug. However, the existing literature on this topic is limited. Therefore, we conducted a study using VigiBase® to investigate the potential over-reporting of infections associated with clozapine, to explore the presence of dose-dependency, and to investigate the underlying mechanism. Methods: Disproportionality analyses were performed using VigiBase to assess the association between clozapine and all types of infections, the association between clozapine-associated infections and neutropenia, the association between clozapine-associated infections and agranulocytosis, the dose-effect relationship between clozapine and infections, and the interaction between clozapine and the main strong CYP450 inhibitors using reports carried out until 11 April 2023. Results: A statistically significant signal of infections was observed with clozapine, as indicated by an information component of 0.43 [95% CI: (0.41-0.45)]. The most commonly reported infections were respiratory and gastrointestinal in nature. Neutropenia showed weaker association with clozapine-associated reports of infections compared to other clozapine-associated reports [X2 (1, N = 204,073) = 454; p < 0.005], while agranulocytosis demonstrated a stronger association with clozapine-associated reports of infections [X2 (1, N = 204,073) = 56; p < 0.005]. No evidence of dose-dependency was observed. Among the 17 tested CYP inhibitors, significant drug-drug interactions were found with clarithromycin, metronidazole, valproic acid, lansoprazole, omeprazole, amiodarone, and esomeprazole. Discussion: Our study revealed a significant safety signal between clozapine use and infections, predominantly respiratory and gastrointestinal infections. The co-administration of clozapine with valproic acid or proton pump inhibitors may potentially contribute to an increased risk of infection. Further vigilance is warranted in clinical practice, and consideration of therapeutic drug monitoring of clozapine in cases involving concomitant use of these drugs or in the presence of infections may be beneficial.

Project description:IntroductionThe Food and Drug Administration (FDA) Adverse Event Reporting System (FAERS) and VigiBase® are two established databases for safety monitoring of medicinal products, recently complemented with the EudraVigilance Data Analysis System (EVDAS).ObjectiveSignals of disproportionate reporting (SDRs) can characterize the reporting profile of a drug, accounting for the distribution of all drugs and all events in the database. This study aims to quantify the redundancy among the three databases when characterized by two disproportionality-based analyses (DPA).MethodsSDRs for 100 selected products were identified with two sets of thresholds (standard EudraVigilance SDR criteria for all vs Bayesian approach for FAERS and VigiBase®). Per product and database, the presence or absence of SDRs was determined and compared. Adverse events were considered at three levels: MedDRA® Preferred Term (PT), High Level Term (HLT), and HLT combined with Standardized MedDRA® Query (SMQ). Redundancy was measured in terms of recall (SDRs in EVDAS divided by SDRs from any database) and overlap (SDRs in EVDAS and at least one other database, divided by SDRs in EVDAS). Covariates with potential impact on results were explored with linear regression models.ResultsThe median overlap between EVDAS and FAERS or VigiBase® was 85.0% at the PT level, 94.5% at the HLT level, and 97.7% at the HLT or SMQ level. The corresponding median recall of signals in EVDAS as a percentage of all signals generated in all three databases was 59.4%, 74.1%, and 87.9% at the PT, HLT, and HLT or SMQ levels, respectively. The overlap difference is partially explained by the relative number of EU cases in EudraVigilance and the ratio of EVDAS cases and FAERS cases, presumably due to differences in marketing authorizations, or market penetration in different regions. Products with few cases in EVDAS (< 1500) also display limited recall of signals relative to FAERs/VigiBase®. Time-on-market does not predict signal redundancy between the three databases. The choice of the DPA has an expected but somewhat small effect on redundancy.ConclusionsOrganizations typically consider regulatory expectations, operating performance (e.g., positive predictive value), and procedural complexity when selecting databases for signal management. As SDRs can be seen as a proxy of general reporting characteristics identifiable in a systematic screening process, our results indicate that, for most products, these characteristics are largely similar in each of the databases.

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Dataset Information

Fetal and Neonatal Adverse Drug Reactions Associated with Biologics Taken During Pregnancy by Women with Autoimmune Diseases: Insights from an Analysis of the World Health Organization Pharmacovigilance Database (VigiBase^®).

Introduction

Objective

Methods

Results

Conclusion

Publications

Fetal and Neonatal Adverse Drug Reactions Associated with Biologics Taken During Pregnancy by Women with Autoimmune Diseases: Insights from an Analysis of the World Health Organization Pharmacovigilance Database (VigiBase<sup>®</sup>).

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets

Dataset Information

Fetal and Neonatal Adverse Drug Reactions Associated with Biologics Taken During Pregnancy by Women with Autoimmune Diseases: Insights from an Analysis of the World Health Organization Pharmacovigilance Database (VigiBase®).

Introduction

Objective

Methods

Results

Conclusion

Publications

Fetal and Neonatal Adverse Drug Reactions Associated with Biologics Taken During Pregnancy by Women with Autoimmune Diseases: Insights from an Analysis of the World Health Organization Pharmacovigilance Database (VigiBase<sup>®</sup>).

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets

Fetal and Neonatal Adverse Drug Reactions Associated with Biologics Taken During Pregnancy by Women with Autoimmune Diseases: Insights from an Analysis of the World Health Organization Pharmacovigilance Database (VigiBase^®).