Drug Safety最新文献

{"title":"A Scoping Review of Published Literature on the Contributions of the Natural Health Products (NHPs) Industry to Pharmacovigilance for NHPs.","authors":"Xin Yi Lim, Sanyogita Ram, Shane Scahill, Joanne Barnes","doi":"10.1007/s40264-025-01587-w","DOIUrl":"https://doi.org/10.1007/s40264-025-01587-w","url":null,"abstract":"<p><strong>Background: </strong>The natural health products (NHPs) industry is a key stakeholder in pharmacovigilance for NHPs. However, the specific contributions that the NHPs industry makes to pharmacovigilance for NHPs are not well-understood.</p><p><strong>Objective: </strong>This scoping review aimed to identify and map published literature describing the contributions of the NHPs industry to pharmacovigilance activities for NHPs. Assessment of benefit-harm balance for individual NHPs/natural ingredients is outside the scope of this review.</p><p><strong>Methods: </strong>Using predetermined keywords and Medical Subject Headings, seven international electronic biomedical journal databases were searched to identify articles describing the contributions of the NHPs industry to pharmacovigilance for NHPs in relation to product surveillance and stakeholders' views on the NHPs industry and its pharmacovigilance activities.</p><p><strong>Results: </strong>Of the 2285 records identified, 40 articles (representing 40 studies) met the inclusion criteria for this review. Among these, 33 described post-marketing surveillance activities and seven explored stakeholders' views. Of the articles describing post-marketing surveillance studies, 22 were authored and/or sponsored by the industry; the remaining 11 involved contributions from the NHPs industry in the form of safety data submitted as spontaneous reports to a national or state pharmacovigilance database. Contributions of the NHPs industry were primarily through passive surveillance via spontaneous reporting. In total, 13 active surveillance studies were undertaken by the NHPs industry, mainly in clinical care settings such as medical centres, hospitals, and private practices, and were focused on single products. There were limited findings relating to stakeholders' views on pharmacovigilance and the NHPs industry's involvement.</p><p><strong>Conclusions: </strong>The NHPs industry contributes to pharmacovigilance for NHPs primarily through passive surveillance measures. Active surveillance involving the NHPs industry was typically undertaken in non-community settings. Additional research exploring stakeholders' views on and preparedness for participating in active surveillance involving the industry, focusing particularly on models based on the consumer-industry reporting pathway, could identify new strategies for strengthening post-marketing safety monitoring for NHPs.</p>","PeriodicalId":11382,"journal":{"name":"Drug Safety","volume":" ","pages":""},"PeriodicalIF":3.8,"publicationDate":"2025-08-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144798497","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Impact of COVID-19 and COVID-19 Vaccination on Detection, Assessment, and Management of Suspected Acute Drug-Induced Liver Injury Occurring during Clinical Trials: Consensus Recommendations from the IQ DILI Initiative.","authors":"Melissa Palmer, Daniel Seekins, Mark Avigan, John Marcinak, Don C Rockey, Arie Regev, Vineet K Shastri, James H Lewis, Ajit Dash","doi":"10.1007/s40264-025-01591-0","DOIUrl":"https://doi.org/10.1007/s40264-025-01591-0","url":null,"abstract":"<p><p>While the acute impact of the coronavirus disease 2019 (COVID-19) pandemic has waned, implications for clinical trials remain. In particular, guidance for evaluation of elevated liver tests due to COVID-19, its treatments, and COVID-19 vaccination is lacking. The IQ DILI Initiative, composed of experts from academia, regulatory agencies, and industry herein propose recommendations to address this gap. Extensive literature review was conducted and structured discussions were held between IQ DILI industry members, regulators, and academic experts in hepatology and DILI. Liver-related manifestations in nonhospitalized patients with COVID-19 are highly varied. Evidence of liver injury may occur after COVID-19 symptoms resolve and testing is negative. Treatments for COVID-19 may cause liver injury or alter pharmacokinetics. COVID-19 vaccination has been associated with rare but clear hepatotoxicity, typically consistent with drug-induced autoimmune-like hepatitis, although other presentations, severity, latency, and time to resolution have been reported. Liver injury occurred with mRNA and viral vector vaccines, and in individuals with and without underlying autoimmune or liver diseases. Drug developers and investigators should be aware of the potential liver-related manifestations related to COVID-19, its treatments, and COVID-19 vaccination, as this may impact study eligibility and causality assessment during a trial. COVID-19 testing should be considered part of DILI causality assessment, as a positive test may prevent premature termination of the investigational drug. Since clinical trial participants may not consider vaccinations in their medical history, specific inquiry about their receipt is important when liver tests are abnormal during screening and as part of DILI causality assessment.</p>","PeriodicalId":11382,"journal":{"name":"Drug Safety","volume":" ","pages":""},"PeriodicalIF":3.8,"publicationDate":"2025-08-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144783798","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Teratogenic Risk Impact Mitigation (TRIM): Development of Explicit Criteria to Facilitate Decisions Regarding Teratogenic Risk Mitigation Strategies.","authors":"Celeste L Y Ewig, Yanning Wang, Nicole E Smolinski, Gita A Toyserkani, Cynthia LaCivita, Leila Lackey, Sara Eggers, Leyla Sahin, Reem S Abu-Rustum, Brian T Bateman, Anick Berard, Christina D Chambers, Beth Choby, Elizabeth A Conover, Michael F Greene, Sonia Hernández-Díaz, Denise J Jamieson, Sarah G Običan, Janine E Polifka, Kay Roussos-Ross, Jeanne S Sheffield, Sharon Voyer Lavigne, Ellen M Zimmermann, Susan B Laffan, Anthony M DeLise, Alicia W Gilsenan, Tarek A Hammad, Christian Hampp, Janet R Hardy, Caitlin A Knox, Kristine Shields, Meredith Y Smith, Rachel E Sobel, Melissa S Tassinari, Judith C Maro, Sonja A Rasmussen, Almut G Winterstein","doi":"10.1007/s40264-025-01581-2","DOIUrl":"https://doi.org/10.1007/s40264-025-01581-2","url":null,"abstract":"<p><strong>Background: </strong>Preventing fetal exposure to teratogenic medications is an important target for risk mitigation efforts. Decisions about risk mitigation efforts specific to teratogenic medications are complex.</p><p><strong>Objectives: </strong>The Teratogenic Risk Impact and Mitigation (TRIM) tool was developed as an innovative decision support tool to facilitate prioritization of teratogenic medications for risk mitigation strategies.</p><p><strong>Methods: </strong>We employed a modified Delphi study design involving experts across teratology, obstetrics/gynecology, and medication safety. Panelists proposed decision criteria in three focus groups, followed by e-Delphi rounds to reach a consensus on criteria regarding three dimensions: (1) completeness; (2) relevance; and (3) distinctiveness. Aggregated feedback from each round was used to inform revision of the criteria in subsequent rounds.</p><p><strong>Results: </strong>A total of 33 candidate criteria proposed by 32 focus group participants were organized into ten distinct criteria for the Delphi process. Consensus (defined as > 85% agreement on all three dimensions) was reached after three e-Delphi rounds, resulting in six criteria: (1) background use among persons of reproductive potential; (2) overall medication benefit considering severity of the indication and availability of alternatives; (3) seriousness of the teratogenic outcome; (4) risk of the teratogenic outcome; (5) certainty regarding teratogenicity; and (6) the risk of exposure during pregnancy.</p><p><strong>Conclusions: </strong>We established measurable criteria to inform decisions when prioritizing teratogenic medications for risk mitigation programs. Criteria are consensus based and consistent with relevant regulatory guidance. Future work will operationalize these criteria and determine specific weights to facilitate medication-specific TRIM scores. Through its explicit framework, the TRIM tool may support consistent, transparent, and rational decision making and help optimize the contribution of risk mitigation programs to public health.</p>","PeriodicalId":11382,"journal":{"name":"Drug Safety","volume":" ","pages":""},"PeriodicalIF":3.8,"publicationDate":"2025-08-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144783797","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"How does the Content and Dissemination of Communications on the Risks of Medicines Affect Prescriber Awareness, Knowledge, and Behaviour: A Systematic Review.","authors":"Lucy T Perry, Annim Mohammad, Ashleigh Hooimeyer, Eliza J McEwin, Barbara Mintzes","doi":"10.1007/s40264-025-01588-9","DOIUrl":"https://doi.org/10.1007/s40264-025-01588-9","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Background: &lt;/strong&gt;Medicines have important and sometimes lifesaving health benefits. They can also be the cause of harm and injury due to adverse drug reactions (ADRs). Effective communication of medicine risks is crucial to informed prescribing decisions and the protection of patient health. Clinicians must receive, interpret, and then implement these communications to achieve desired outcomes; however, this has not always been successful. Therefore, it is important to understand how the content of risk communication about medicines and the methods of dissemination may affect prescribers' awareness, knowledge, and behaviours.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Aims: &lt;/strong&gt;This systematic review provides an overview of the effect of content and dissemination of risk communications about medicines on prescribers' awareness, knowledge, and behaviour and ultimately on patient health.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Methods: &lt;/strong&gt;A systematic review was conducted. Studies were included if they were randomised controlled trials investigating the effect of the content or dissemination of risk communications about medicines on prescribers' knowledge, awareness, and behaviour. MEDLINE, Embase, and PsycINFO via Ovid, Scopus, and Web of Science databases were searched up to December 2024. Data on intervention type, study design, prescriber type, and outcomes were extracted. Outcomes were synthesised, and meta-analysis was undertaken where results allowed for this.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Results: &lt;/strong&gt;Twenty-three studies met the inclusion criteria: ten investigated the content of risk communication, ten investigated dissemination methods, and three investigated both. Twenty-one studies assessed prescribing behaviours, and one study each assessed clinicians' awareness and knowledge, respectively. Two studies evaluated how risk communication content and its delivery to clinicians affected patient health outcomes. Interventions included computerised clinical systems, risk assessment tools, alerting systems, targeted messaging, and education. Visual risk assessment tools and targeted education reduced ADR rates, improving patient health. Alerts to change clinical monitoring and assessment behaviour were modestly effective (relative risk [RR] 1.03; 95% confidence interval [CI] 1.01-1.05). Multicomponent approaches also positively affected prescribing behaviours. Targeted messages, such as audit and feedback, improved clinicians' awareness of risk communications. Computer alerts and risk assessments that were interruptive and easily accessed in workflows or provided actions or information to avoid or minimise risk to patients did not significantly change prescribing (RR 1.50; 95% CI 0.87-2.60 and RR 1.41; 95% CI 0.89-2.24). However, study heterogeneity and small sample sizes limited the power to detect differences.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Conclusion: &lt;/strong&gt;There is limited evidence from randomised controlled trials comparing the effectiveness of drug risk communication strategies targeting p","PeriodicalId":11382,"journal":{"name":"Drug Safety","volume":" ","pages":""},"PeriodicalIF":3.8,"publicationDate":"2025-08-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144774936","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Uncovering the Hidden Hurdles: Exploring Challenges in Pediatric Pharmacovigilance in the Netherlands.","authors":"Anne T M Dittrich, Yvet Kroeze, Michel A A P Willemsen, Jos M Th Draaisma, Eugène P van Puijenbroek, D Maroeska W M Te Loo","doi":"10.1007/s40264-025-01593-y","DOIUrl":"https://doi.org/10.1007/s40264-025-01593-y","url":null,"abstract":"<p><strong>Introduction: </strong>The use of drugs carries risks, as adverse drug reactions (ADRs) can occur. In the Netherlands, a voluntary pharmacovigilance system is in place, allowing healthcare professionals and patients to report (suspected) ADRs. Previous research has highlighted underreporting as a significant problem; however, barriers for ADR reporting are not clear.</p><p><strong>Objectives: </strong>The aim was to assess perceptions of ADR reporting among pediatricians (in training), to identify barriers hindering reporting, and to study differences between our hospital and other Dutch hospitals.</p><p><strong>Methods: </strong>A cross-sectional survey was conducted among pediatricians (in training) in the Netherlands. The study questionnaire was based on a validated questionnaire and adjusted for the Dutch context, addressing aspects related to ADR reporting, attitudes toward ADRs in work environment, personal vision, reasons for nonreporting, and future perspectives.</p><p><strong>Results: </strong>A dataset of 127 respondents was included. Of these, 93% reported knowing how to report an ADR. Overall, 95% believed that reporting ADRs has the potential to enhance knowledge and improve drug safety, and 93% acknowledged the overall importance of ADR reporting. However, 19% of respondents indicated that they had never reported an ADR. The most commonly cited reason (61%) for not reporting was prior knowledge of the ADR. Other barriers included uncertainty about whether a symptom constituted an ADR, the perception that the ADR was not severe, and time constraints.</p><p><strong>Conclusions: </strong>This study highlights the importance of addressing barriers to ADR reporting in pediatric healthcare. While healthcare professionals recognize the significance of ADR reporting, several impediments hinder their reporting efforts.</p>","PeriodicalId":11382,"journal":{"name":"Drug Safety","volume":" ","pages":""},"PeriodicalIF":3.8,"publicationDate":"2025-08-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144768486","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Might We Come Together on a Paradigm Shift to Manage ICSRs with a Decentralized Data Model?","authors":"Lucinda Smith, Michael Glaser, Dieter Kempf, Xaymara Roman, Charlotte Artlich, Mayur A Patel, Andrew Bate","doi":"10.1007/s40264-025-01539-4","DOIUrl":"10.1007/s40264-025-01539-4","url":null,"abstract":"<p><p>The current practice of managing and sharing individual case safety reports (ICSRs) across the patient safety ecosystem, established in the 1960s, has become burdened with ICSR duplication and replication and can result in a fragmented understanding of product safety profiles. For this article, we have defined duplication as multiple representations of the same case within the same database and replication as various representations of the same case across numerous databases. Evolving safety regulations and increasing case volumes signal a need for a new path forward that is sustainable and enhances public health. While there is no question that ICSRs are a crucial component of safety surveillance, stakeholders must evaluate their management to ensure they are fit for purpose in a modern ecosystem. This article aims to embark on that path by proposing a conceptual decentralized ICSR management model to facilitate multi-stakeholder collaboration around new working models to mitigate duplication and replication, allow ecosystem stakeholders to access the latest source of truth on demand, facilitate more meaningful safety analysis and interpretation, and ultimately enable a real-time learning healthcare system to improve patient safety and health outcomes. It describes the feasibility analysis results and subsequently conducted proof of concept (PoC) based on a decentralized system architecture supporting such a decentralized model. It outlines considerations, challenges, and opportunities compared with the current state related to case management and signal management processes.</p>","PeriodicalId":11382,"journal":{"name":"Drug Safety","volume":" ","pages":"843-853"},"PeriodicalIF":4.0,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12259765/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143582184","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"IQ DILI Consensus Opinion: Best Practices for Rechallenge Following Suspected Drug-Induced Liver Injury in Clinical Trials.","authors":"Klaudia Steplewski, Lucy Walker, Nefeteria Coffee, Maura Fallon, Rie Yonemochi, David Alpers, Don Rockey, James Lewis, Eric Cohen, John Caminis, Judith Hey-Hadavi, Raul Jesus Andrade, Melissa Palmer","doi":"10.1007/s40264-025-01540-x","DOIUrl":"10.1007/s40264-025-01540-x","url":null,"abstract":"<p><p>Rechallenge with study drug after suspected drug-induced liver injury (DILI) during drug development requires a comprehensive assessment of risks and benefits. Lack of universal consensus or societal guidelines makes this decision-making process more challenging and difficult to manage in clinical development. The sparse published literature is biased towards reporting cases of positive rechallenge (recurrent DILI), often with adverse outcomes. The heterogeneity of available data and inconsistent approaches to drug rechallenge likely lead to bias in our perception of the risks of rechallenge, ultimately leaving this topic controversial. The IQ DILI Causality Assessment Working Group, in collaboration with academic and regulatory experts, developed this manuscript with the following objectives: (1) understand and describe current practices via literature review and survey of practices and opinions among drug developers, academic experts, and regulators; (2) propose a consistent and structured approach to decision-making and managing the rechallenge process; (3) facilitate better understanding of the risks and benefits of rechallenge via a standardized approach to collecting rechallenge data, including outcomes and the importance of publishing rechallenge data; and (4) the role of obtaining a liver biopsy, guidance on when a biopsy might be considered, and what histologic findings can assist in making the rechallenge decision. Lastly, knowledge gaps in the drug rechallenge paradigm are highlighted alongside the proposal to standardize the collection and publication of rechallenge data to help address these gaps. This consensus expert opinion does not encourage rechallenge but provides guidance for drug developers to apply a consistent approach to rechallenge.</p>","PeriodicalId":11382,"journal":{"name":"Drug Safety","volume":" ","pages":"855-874"},"PeriodicalIF":4.0,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12259801/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143771407","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Investigating Risk of Cancer with Sodium-Glucose Cotransporter 2 Inhibitors: A Disproportionality Analysis in the WHO Global Pharmacovigilance Database Vigibase^®.","authors":"Paul Gautier, Meyer Elbaz, Frédéric Bouisset, Fabien Despas, François Montastruc","doi":"10.1007/s40264-025-01546-5","DOIUrl":"10.1007/s40264-025-01546-5","url":null,"abstract":"<p><strong>Introduction: </strong>Use of sodium-glucose cotransporter 2 inhibitors (SGLT-2is) has significantly increased due to their cardiovascular benefits. Whether SGLT-2is increase risk of cancer has been of concern since first clinical trials, but this question remains unclear because of methodological limitations in previous studies.</p><p><strong>Methods: </strong>We conducted a disproportionality analysis using Vigibase^® between 2014 and 2023 to estimate the association between SGLT-2i use and the risk of reporting of different subtypes of cancers, compared with glucagon like peptide-1 (GLP-1) analogues and dipeptidyl peptidase-4 (DPP-4) inhibitors.</p><p><strong>Results: </strong>Among 644 reported cases of cancer associated with SGLT-2i use, 427 (66.3%) were male, with a mean age of 66.5 ± 9.7 years. Sodium-glucose cotransporter 2 inhibitors showed increased reporting odds ratio for bladder cancer (ROR 4.46, 95% CI 3.23-6.17) and kidney cancer (ROR 1.84, 95% CI 1.25-2.69), but not for all other cancer subtypes.</p><p><strong>Conclusion: </strong>In this disproportionality analysis with a hypothesis-generating approach, SGLT-2is are associated with an increased risk of reporting bladder and kidney cancer. There is a need of an urgent clarification of this signal with further long-term observational studies.</p>","PeriodicalId":11382,"journal":{"name":"Drug Safety","volume":" ","pages":"933-941"},"PeriodicalIF":4.0,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12259762/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143977716","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Signal Monitoring for Adverse Events Following Immunisation with COVID-19 Vaccines During the SARS-CoV-2 Pandemic: An Evaluation of the South African Surveillance System.","authors":"Chenoa Sankar, Stephen Evans, Johanna Catharina Meyer, Hannah May Gunter, Victoria Sekiti, Kerrigan McCarthy","doi":"10.1007/s40264-025-01547-4","DOIUrl":"10.1007/s40264-025-01547-4","url":null,"abstract":"<p><strong>Introduction: </strong>Monitoring of adverse events following immunisation (AEFI) is recommended for post-licensure surveillance. We investigated whether the South African surveillance system could detect signals of disproportionate reporting and whether these signals aligned with globally identified AEFI and adverse events of special interest (AESI) post-coronavirus disease-2019 (COVID-19) vaccination.</p><p><strong>Methods: </strong>This retrospective pharmacovigilance study undertook disproportionality analysis of the National Department of Health AEFI database from the start of the COVID-19 vaccine rollout on 17 May 2021 to 31 December 2022. We complemented this with AEFI reports for vaccines not on the routine Expanded Programme on Immunisation schedule, to address potential masking of signals due to the high reporting rate of COVID-19 vaccine AEFI.</p><p><strong>Results: </strong>During the study period, 3846 AEFI were reported for 37,537,009 doses of COVID-19 vaccines (BNT162b2 and Ad26.COV2.S) administered. The overall reporting rate was 10.2 per 100,000 doses, 18.1/100,000 and 7.9/100,000 for Ad26.COV2.S and BNT162b2, respectively. Comparison with other countries suggests underreporting. Disproportionate reporting signals were obtained for three and seven AEFI following BNT162b2 and Ad26.COV2.S vaccines, respectively. An additional three AEFI signals from Ad26.COV2.S emerged in the augmented dataset, indicating masking. All Ad26.COV2.S signals, and one BNT162b2 signal, appear in the vaccines' product information. Among nine AESI evaluated, myocarditis/pericarditis presented as a signal of disproportionate reporting following BNT162b2 vaccination.</p><p><strong>Conclusions: </strong>This study is one of the first from a lower-middle-income country, using a spontaneous reporting system for signal detection post-COVID-19 vaccination. Signals aligned with those reported globally. The study highlights the need to further investigate underreporting, masking, and system attributes for system strengthening.</p>","PeriodicalId":11382,"journal":{"name":"Drug Safety","volume":" ","pages":"909-922"},"PeriodicalIF":4.0,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12259799/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143987243","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Major Adverse Cardiovascular Events Related to JAK Inhibitors: A Disproportionality Analysis Using the WHO Global Individual Case Safety Database.","authors":"Raffaella Di Napoli, Christophe Richez, Cristina Scavone, Allison Singier, Maxime Demourgues, Annamaria Mascolo, Annalisa Capuano, Francesco Salvo","doi":"10.1007/s40264-025-01535-8","DOIUrl":"10.1007/s40264-025-01535-8","url":null,"abstract":"<p><strong>Background: </strong>Rheumatoid arthritis (RA) is commonly treated with Janus kinase inhibitors (JAKis) and anti-tumor necrosis factor-α (anti-TNFα), but the cardiovascular safety profiles of these drugs remain unclear.</p><p><strong>Objective: </strong>The aim of this study was to describe the individual case safety reports of major adverse cardiac events (MACE) or stroke and to determine whether there was a difference in the frequency of reporting of cardiovascular events between JAKis and anti-TNFα used in RA.</p><p><strong>Methods: </strong>A case/non-case study was conducted using the WHO VigiBase^® database. Descriptive analysis was performed, the time to onset (TTO) of MACE was calculated, and the reporting odds ratio (ROR) was used to estimate the frequency of MACE reports associated with JAKis versus anti-TNFα in RA.</p><p><strong>Results: </strong>A total of 18,099 cases of MACE were identified, of which 2543 (14%) were associated with JAKis, predominantly in women (65.4%) and in patients aged ≥65 years (49.9%). The median time to onset was 210 days (IQR 60-510) for JAKis and 690 days (210-1460) for anti-TNFα. JAKis were associated with higher odds of reporting MACE (ROR 1.38 [95% CI 1.32-1.44]), mainly due to non-fatal stroke (1.65 [1.55-1.75]). Stroke as a whole showed similar results (1.62 [1.53-1.72]). The ROR of MACE was also slightly increased in patients aged <65 years treated with JAKis (1.29 [1.21-1.39]).</p><p><strong>Conclusions: </strong>Compared with anti-TNFα, JAKis were more associated with MACE, especially stroke, and with a shorter time to onset. These data support the hypothesis of a different cardiovascular reporting frequency between JAKis and anti-TNFα. In patients with identified cardiovascular risk, anti-TNFα should be preferred to JAKis until more definitive results are available.</p>","PeriodicalId":11382,"journal":{"name":"Drug Safety","volume":" ","pages":"943-952"},"PeriodicalIF":4.0,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12259736/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143691565","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}