Drug Safety最新文献

{"title":"Assessment of Pharmacovigilance Across University Hospitals in Morocco.","authors":"Hind Hamzaoui, Anna Shaum, Imad Cherkaoui, Latifa Ait Moussa, Houda Sefiani, Ismail Talibi, Ghita Benabdallah, Omar Salman, Seth Ferrey, Rachida Soulaymani Bencheikh","doi":"10.1007/s40264-025-01517-w","DOIUrl":"https://doi.org/10.1007/s40264-025-01517-w","url":null,"abstract":"<p><strong>Introduction: </strong>Despite the increased scrutiny on vaccine safety following the coronavirus disease 2019 (COVID-19) pandemic, Morocco's Centre of Antipoison and Pharmacovigilance (CAPM) remained concerned that the pharmacovigilance system in Morocco was insufficiently implemented, including limited adverse event (AE) reporting, poor data use, and inconsistent training nationwide.</p><p><strong>Objectives: </strong>We sought to assess the status of pharmacovigilance activities (PAs) prior to formally institutionalizing them across university hospital centers (UHCs), given their position as the main providers of healthcare in Morocco and key sources for reporting serious AEs.</p><p><strong>Methods: </strong>We assessed seven UHCs (housing 30 hospitals) in 2023 using a structured questionnaire with pharmacovigilance focal points developed from the World Health Organization's indicators of pharmacovigilance and the Global Benchmarking Tool. Data were grouped into 28 PAs and scored from 0 (not implemented) to 3 (fully implemented). We then calculated an implementation rate for each site on the basis of percent of PAs fully implemented (≥ 70%, well established; > 40% to < 70%, partially implemented; and ≤ 40%, not implemented). A desk review was also performed at the sites. Using the results of the assessment, three working groups of pharmacovigilance stakeholders developed recommendations to be formally adopted by UHCs.</p><p><strong>Results: </strong>Basic elements of pharmacovigilance (notification forms and VigiFlow^® or Excel databases) were present at all the UHCs assessed. In total, 14 hospitals (47%) had well-established PAs, including advanced activities such as signal detection of adverse events following the use of medicines and vaccines, as well as causality assessment; 9 hospitals (30%) were partially implementing pharmacovigilance, and 7 hospitals (23%) had no established activities or very basic activities. Within four UHCs, activities had not been implemented at the same level from one hospital to another and vaccine vigilance was largely deprioritized. The working groups made recommendations for improving collaboration, standardizing procedures, and outlining a new organizational structure for pharmacovigilance, which was institutionalized by a formal agreement among UHCs in July 2023.</p><p><strong>Conclusions: </strong>The assessment revealed a subgroup of centers with well-established AE signal detection and causality assessment abilities, which could play a leading role in the country. After the site assessment, our collaborative approach of bringing together focal points to identify next steps and generate buy-in helped to formalize pharmacovigilance across centers.</p>","PeriodicalId":11382,"journal":{"name":"Drug Safety","volume":" ","pages":""},"PeriodicalIF":4.0,"publicationDate":"2025-02-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143406395","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":"Emerging Tools to Support DILI Assessment in Clinical Trials with Abnormal Baseline Serum Liver Tests or Pre-existing Liver Diseases.","authors":"Jasmine Amirzadegan, Bereket Tesfaldet, Y Veronica Pei, Eileen Navarro Almario, Mark I Avigan, Paul H Hayashi","doi":"10.1007/s40264-024-01511-8","DOIUrl":"https://doi.org/10.1007/s40264-024-01511-8","url":null,"abstract":"<p><p>Based on the late Dr. Hyman Zimmerman's observation that hepatocellular drug-induced liver injury (DILI) leading to jaundice carries a ≥ 10% fatality risk (coined as Hy's law by others), evaluation of Drug-Induced Serious Hepatotoxicity (eDISH) continues to play a central role in the assessment of a study drug's liability for acute hepatocellular DILI. The eDISH identifies drugs in clinical trials with DILI fatality (death or transplant) risk that may be unacceptable in a post-market setting. As a two-dimensional graph that plots peak total bilirubin (TB) versus peak serum aminotransferase levels for each patient during study drug or comparator treatment, eDISH identifies potential cases of acute, modest, and serious hepatocellular DILI for in-depth analysis of liver tests (LT) and clinical course so that the likelihood of causal association with the study drug can be determined. Unfortunately, the generalizable utility of this tool only pertains to trials enrolling patients with normal or near normal (NNN) baseline (BL) serum LTs. The eDISH does not necessarily apply to trials of patients with abnormal baseline (ABN-BL) LTs that often coincide with underlying liver disorders. Because drug development programs being reviewed by the FDA increasingly target liver disorders, we are often challenged to evaluate DILI risk in trials of patients with ABN-BL LTs. Also, the high background prevalence of metabolic dysfunction associated steatotic liver disease (MASLD) means patients with LTs above NNN may need to be enrolled in trials treating non-liver disorders to reflect the target population. Such study populations create challenges for industry and regulators because eDISH may not reliably categorize or identify potential cases of DILI for further analysis, as it so efficiently does in NNN-BL trials. We describe the main functionalities of eDISH in NNN-BL trials to understand what should be emulated by new tools or eDISH modifications. We then discuss non-eDISH-based plots that may be useful in ABN-BL trials.</p>","PeriodicalId":11382,"journal":{"name":"Drug Safety","volume":" ","pages":""},"PeriodicalIF":4.0,"publicationDate":"2025-02-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143390510","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":"Risk of Fracture Associated with Pregabalin or Mirogabalin Use: A Case-Case-Time-Control Study Based on Japanese Health Insurance Claims Data.","authors":"Hinako Wakabayashi, Toshiki Fukasawa, Satomi Yoshida, Kairi Ri, Soichiro Masuda, Takayuki Anno, Koji Kawakami","doi":"10.1007/s40264-025-01516-x","DOIUrl":"https://doi.org/10.1007/s40264-025-01516-x","url":null,"abstract":"<p><strong>Background: </strong>Pregabalin is widely used for neuropathic pain. Mirogabalin, a newer gabapentinoid, was recently introduced in several Asian countries. A previous case-crossover study showed an association between pregabalin and fall-related injuries, but the findings may have been affected by biases from individual- and population-level exposure time trends, and generalizability was limited due to a focus on a middle-aged population. Further, no findings have appeared on mirogabalin and its association with fall-related fractures.</p><p><strong>Objective: </strong>We conducted a case-case-time-control study to investigate the risk of fracture associated with pregabalin and mirogabalin in a population with broad demographic coverage.</p><p><strong>Methods: </strong>Incident fractures were identified from a Japanese claims database. For each case, hazard (days 1-30 before the fracture event) and control windows (days 61-90 before the event) were set. Each current case was matched by age and sex to a future case, defined as a patient who experienced a fracture 120-365 days later. Odds ratios (ORs) were estimated using conditional logistic regression models.</p><p><strong>Results: </strong>A total of 814,216 and 460,811 cases were included in the pregabalin and mirogabalin analyses, respectively. ORs were 1.35 (95% confidence interval 1.28-1.43) for pregabalin and 1.53 (1.35-1.72) for mirogabalin, indicating an increased risk of fracture with both drugs. These results remained consistent and robust across sensitivity and subgroup analyses, except in patients under 65 years of age.</p><p><strong>Conclusion: </strong>Given this observed risk and the fact that these medications are commonly prescribed to older populations, caution is warranted in clinical use.</p>","PeriodicalId":11382,"journal":{"name":"Drug Safety","volume":" ","pages":""},"PeriodicalIF":4.0,"publicationDate":"2025-02-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143398782","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":"Drug Induced Liver Injury: Highlights and Controversies in the 2023 Literature.","authors":"Harjit Singh, Bryce F Kunkle, Angela R Troia, Advait M Suvarnakar, Ade C Waterman, Yadana Khin, Serena Y Korkmaz, Corinne E O'Connor, James H Lewis","doi":"10.1007/s40264-025-01514-z","DOIUrl":"https://doi.org/10.1007/s40264-025-01514-z","url":null,"abstract":"<p><p>Drug-induced liver injury (DILI) remains an active field of clinical research and investigation with more than 4700 publications appearing in 2023 relating to hepatotoxicity of all causes and injury patterns. As in years past, we have attempted to identify and summarize highlights and controversies from the past year's literature. Several new and novel therapeutic agents were approved by the US Food and Drug Administration (FDA) in 2023, a number of which were associated with significant hepatotoxicity. Updates in the diagnosis and management of DILI using causality scores as well as newer artificial intelligence-based methods were published. Details of newly established hepatotoxins as well as updated information on previously documented hepatotoxic drugs is presented. Significant updates in treatment of DILI were also included as well as reports related to global DILI registries.</p>","PeriodicalId":11382,"journal":{"name":"Drug Safety","volume":" ","pages":""},"PeriodicalIF":4.0,"publicationDate":"2025-02-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143373832","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":"Network Analysis and Machine Learning for Signal Detection and Prioritization Using Electronic Healthcare Records and Administrative Databases: A Proof of Concept in Drug-Induced Acute Myocardial Infarction.","authors":"Maria Antonietta Barbieri, Andrea Abate, Olivér M Balogh, Mátyás Pétervári, Péter Ferdinandy, Bence Ágg, Vera Battini, Marianna Cocco, Andrea Rossi, Carla Carnovale, Manuela Casula, Edoardo Spina, Maurizio Sessa","doi":"10.1007/s40264-025-01515-y","DOIUrl":"https://doi.org/10.1007/s40264-025-01515-y","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Background: &lt;/strong&gt;Safety signals for potential drug-induced adverse events (AEs) typically emerge from multiple data sources, primarily spontaneous reporting systems, despite known limitations. Increasingly, real-world data from sources such as electronic health records (EHRs) and administrative databases are leveraged for signal detection. Although network analysis has shown promise in mapping relationships between clinical attributes for signal detection in spontaneous reporting system databases, its application in real-world data from EHRs and administrative databases remains limited.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Objective: &lt;/strong&gt;This study aimed to evaluate the performance of network analysis in detecting safety signals within Italian administrative databases, using drug-induced acute myocardial infarction (AMI) as a proof of concept.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Methods: &lt;/strong&gt;We employed a case-crossover design to explore the association between drug exposure and AMI using the Healthcare Administrative Database of Mantova, Italy, from 2014 to 2018. Patients with their first AMI hospitalization were identified after a 365-day washout period to exclude prior hospitalizations. We constructed a network to analyse the relationships between prescribed drugs and diagnoses, represented as nodes, with undirected edges illustrating their interactions. For each patient with AMI, we identified all diagnoses and drugs recorded or redeemed within 365 days of the first AMI episode and generated various drug-diagnosis, drug-drug, and diagnosis-diagnosis pairs. We calculated the frequency of these pairs, and three types of edge weights quantified the strength of connections. We identified outlier drug-AMI pairs using a predictive score (F) based on frequency (C) and full edge weights (W&lt;sub&gt;F&lt;/sub&gt;), with validation for known AMI associations. We prioritized signals using the F score, C of AMI, and W&lt;sub&gt;F&lt;/sub&gt;, analysed through k-means clustering to identify patterns in the data.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Results: &lt;/strong&gt;From 2014 to 2018, a total of 3918 patients had an AMI, with 4686 AMI diagnoses. Of those, 2866 had prescriptions in the previous year, totalling 498,591 prescriptions. A network analysis identified 2968 unique nodes, revealing 529,935 diagnosis-diagnosis connections, 235,380 drug-diagnosis connections, and 102,831 drug-drug connections. The median number of connections (C) was 404 (Q1-Q3: 194-671) for drug nodes and 380 (Q1-Q3: 216-664) for diagnosis nodes. The median W&lt;sub&gt;F&lt;/sub&gt; was 11.8 (Q1-Q3: 9-14), and the median F score across pairs was 0.1 (Q1-Q3: 0.1-0.3). A total of 249 potential safety signals were detected, with 63.4% aligning with known AEs. Among the remaining signals, 80 were prioritized, and five emerged as the highest priority: terazosin, tamsulosin, allopurinol, esomeprazole, and omeprazole.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Conclusions: &lt;/strong&gt;Overall, our novel method demonstrates that network analysis is a valuable tool for signal detection and prioriti","PeriodicalId":11382,"journal":{"name":"Drug Safety","volume":" ","pages":""},"PeriodicalIF":4.0,"publicationDate":"2025-02-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143364029","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":"A Longitudinal Post-authorization Safety Study of Golimumab in Treatment of Ulcerative Colitis: A Cohort Study in Denmark and Sweden, 2013-2021.","authors":"Annette Kjær Ersbøll, Zhiping Huang, Deanna D Hill, Simone Møller Hede, Vibeke Andersen, Kristian Bolin, Marie Skov Kristensen, Suzan Esslinger, Frida Richter Hansen, Erik Hertervig, Lila Kallio, Thora Majlund Kjærulff, Stine Kloster, Alexis Krumme, James D Lewis, Laila Mehkri, Niels Qvist, Lau Caspar Thygesen, Cindy Weinstein, Anders Green","doi":"10.1007/s40264-025-01519-8","DOIUrl":"https://doi.org/10.1007/s40264-025-01519-8","url":null,"abstract":"<p><strong>Background: </strong>When golimumab (GLM) was approved for the treatment of moderate to severe ulcerative colitis (UC) in 2013, a post-authorization safety study was conducted.</p><p><strong>Objective: </strong>Our objective was to examine whether exposure to GLM was associated with an increased incidence of all-cause total colectomy, colorectal cancer, and hepatosplenic T-cell lymphoma in Denmark and Sweden.</p><p><strong>Methods: </strong>We conducted a new-user, active comparator cohort study of patients with UC in 2013-2021. Exposure to GLM, other anti-tumor necrosis factor (TNF) agents (infliximab and adalimumab) and thiopurines was a time-varying variable. Therapies were based on prescription redemptions and hospital-based administration of medications from national prescription and hospital registers. The association between exposure to study therapies and outcomes was evaluated using Poisson regression of incidence rates (IRs), presented as IR ratios (IRRs) and 95% confidence intervals (CIs).</p><p><strong>Results: </strong>A total of 5177 and 7469 patients were included in Denmark and Sweden, respectively. The IR of all-cause total colectomy per 1000 person-years was higher in Denmark (IR 42.6; 95% CI 38.9-46.2) than in Sweden (IR 16.1; 95% CI 14.2-18.0). No significant difference was observed in all-cause total colectomy between GLM and other anti-TNF agents (Denmark: adjusted IRR [aIRR] 1.28; 95% CI 0.98-1.66; Sweden: aIRR 1.17; 95% CI 0.72-1.90). A significant difference was observed between GLM and thiopurines (Denmark: aIRR 13.62; 95% CI 8.73-21.26; Sweden: aIRR 4.52; 2.75-7.41). Privacy regulations prevented analysis of a few colorectal cancer events. No hepatosplenic T-cell lymphoma events were identified.</p><p><strong>Conclusion: </strong>The IR of all-cause total colectomy with GLM was similar to that with other anti-TNF agents but was much higher than with thiopurines, probably related to confounding by indication.</p>","PeriodicalId":11382,"journal":{"name":"Drug Safety","volume":" ","pages":""},"PeriodicalIF":4.0,"publicationDate":"2025-02-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143255027","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":"Delphi Method Consensus on Statistical Analysis and Reporting Recommendations for Single-Arm Pregnancy Medication Safety Studies Investigating Pregnancy, Birth and Neonatal Health Outcomes: A Contribution from IMI-ConcePTION.","authors":"Jonathan L Richardson, Alan Moore, Michael Stellfeld, Yvonne Geissbühler, Ursula Winterfeld, Guillaume Favre, Christina Chambers, Evelin Beck, Marlies Onken, Katarina Dathe, Michael Ceulemans, Orna Diav-Citrin, Svetlana Shechtman, Alison M Oliver, Kenneth K Hodson, Dee-Dee Shiller, Amalia Alexe, Eugène P van Puijenbroek, David J Lewis, Laura M Yates","doi":"10.1007/s40264-025-01521-0","DOIUrl":"https://doi.org/10.1007/s40264-025-01521-0","url":null,"abstract":"<p><strong>Background and objective: </strong>Standardised procedures for performing and reporting safety monitoring studies investigating medications use in pregnancy may help improve data quality and the speed of data generation. The objective of this study was to provide recommendations on the statistical analysis and reporting of single-arm pregnancy medication safety studies using primary source datasets.</p><p><strong>Methods: </strong>A Delphi consensus-setting protocol was used to acquire agreement on recommendations from experts with extensive knowledge and experience in conducting studies investigating medication safety in pregnancy. A series of recommendations, along with their scientific justifications and examples of how to calculate and describe exposure and outcome incidences, were critiqued and improved through a series of online Delphi review rounds. Agreement to inclusion scoring was assessed using a five-point Likert scale. Recommendations with a median Likert-scale score of at least 4, where ≥ 80% of the expert panel scored the recommendation at level 4 or higher, was used as the threshold for inclusion.</p><p><strong>Results: </strong>The Delphi consensus methodology produced a set of 30 recommendations spread over five themes. These included descriptions of (1) study sample, (2) medication exposure, (3) maternal outcomes, (4) pregnancy and birth outcomes, and (5) fetal and neonatal outcomes. Of the 30 recommendations, 19 were strongly advised while 11 were included for consideration where their implementation may be beneficial for supplementing data communication.</p><p><strong>Conclusion: </strong>Use of the finalised set of recommendations should be encouraged to help standardise published evidence around medication use in pregnancy.</p>","PeriodicalId":11382,"journal":{"name":"Drug Safety","volume":" ","pages":""},"PeriodicalIF":4.0,"publicationDate":"2025-02-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143187677","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":"Views on the Development and Use of a New Digital Adverse Drug Event Reporting Platform in Australia: A Qualitative Study.","authors":"Eyob Alemayehu Gebreyohannes, Christopher Thornton, Myra Thiessen, Sieta T de Vries, Gretchen Coombs, Indae Hwang, Renly Lim","doi":"10.1007/s40264-024-01489-3","DOIUrl":"10.1007/s40264-024-01489-3","url":null,"abstract":"<p><strong>Background: </strong>Reporting of adverse drug events (ADEs) to regulatory authorities remains low, particularly among consumers.</p><p><strong>Objectives: </strong>To explore stakeholders' views on the development and use of a digital platform to improve ADE reporting by consumers to the regulatory authority in Australia, i.e., the Therapeutic Goods Administration.</p><p><strong>Methods: </strong>A qualitative study was conducted using semi-structured interviews, focus group discussions (FGDs), and co-design workshops with consumers, healthcare professionals (HCPs), and regulators. The interview recordings were transcribed verbatim, coded, and analysed thematically according to the Capability, Opportunity, Motivation, Behaviour model. Findings of the FGDs and co-design workshops were incorporated to enhance and complement the insights gathered from the interviews.</p><p><strong>Results: </strong>A total of 39 participants took part in the study (54 % consumers, 41 % HCPs, and 5 % regulators). Uncovered themes related to ADE reporting in general were: difficulty recognizing ADEs and health literacy, awareness about reporting ADEs (Capability); visibility of ADE reporting, professionals' views on consumer ADE reporting, consumer education (Opportunity); the common good, benefit to the reporter, identifying ADEs worth reporting, and concern about reporting (Motivation). Additional identified themes specific to a new digital platform were: physical abilities (Capability); features that facilitate intuitive use, convenience and accessibility, user experience, integration with existing systems, trust, sharing experiences with others (Opportunity); and concern about using a reporting platform, and feedback loop (Motivation).</p><p><strong>Conclusions: </strong>A cross-section of attitudes and values were obtained regarding ADE reporting in general and a new ADE reporting digital platform for consumers in Australia, which will inform its development, implementation and evaluation.</p>","PeriodicalId":11382,"journal":{"name":"Drug Safety","volume":" ","pages":"179-190"},"PeriodicalIF":4.0,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11785647/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142563849","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":"Incidence of Idiosyncratic Drug-Induced Liver Injury Caused by Prescription Drugs.","authors":"Vincent L Chen, Don C Rockey, Einar S Bjornsson, Huiman Barnhart, Jay H Hoofnagle","doi":"10.1007/s40264-024-01486-6","DOIUrl":"10.1007/s40264-024-01486-6","url":null,"abstract":"<p><strong>Background: </strong>The incidence of drug-induced liver injury (DILI) is not known for most prescription medications. We aimed to estimate the incidence of DILI for commonly prescribed outpatient drugs.</p><p><strong>Methods: </strong>To establish a baseline estimate of DILI incidence, we used the estimated incidence (EI) of amoxicillin/clavulanate DILI from a previous population-based study in Iceland. This was combined with the multicenter prospective DILI Network (DILIN) cohort and the US population-based Medical Expenditure Panel Survey (MEPS). From 2005 to 2019, prescription drugs with at least five bona fide DILIN cases and data from at least 10 of the 15 years from MEPS during that timeframe were included. The EI for 'drug A' was calculated as follows: <math><mrow><mtext>EI</mtext> <mrow><mo>(</mo> <mtext>drug A</mtext> <mo>)</mo></mrow> <mo>=</mo> <mtext>EI</mtext> <mfenced><mtext>AC</mtext></mfenced> <mo>×</mo> <mfrac><mrow><mo>#</mo> <mspace></mspace> <mtext>DILIN cases of drug A</mtext></mrow> <mrow><mo>#</mo> <mspace></mspace> <mtext>annual new prescriptions of drug A</mtext></mrow> </mfrac> <mo>×</mo> <mfrac><mrow><mo>#</mo> <mspace></mspace> <mtext>annual new prescriptions of AC</mtext></mrow> <mrow><mo>#</mo> <mspace></mspace> <mtext>DILIN cases of AC</mtext></mrow> </mfrac> </mrow> </math> RESULTS: In total, 30 drugs met the inclusion criteria, of which 11 were antibiotics, 4 were antiepileptic drugs (AEDs), 4 were statins, and 11 were other drug types. The highest EI was seen with azathioprine and older AEDs, with one DILI case per 349-2329 new prescriptions. The EI of antibiotics ranged greatly, with the highest risk seen for minocycline, amoxicillin/clavulanate, and nitrofurantoin (approximately 1:1000-2400 new prescriptions), and lowest risk for clindamycin, doxycycline, azithromycin, and amoxicillin (approximately 1:40,000-170,000 new prescriptions). The EI for commonly prescribed statins was approximately 1:10,000-50,000. Important medication classes with > 5 million new prescriptions from 2005 to 2019 but fewer than five DILIN cases included β-blockers, thiazide diuretics, angiotensin-converting enzyme inhibitors, angiotensin receptor blockers, selective serotonin reuptake inhibitors, and metformin, which presumably have very low DILI incidence.</p><p><strong>Conclusions: </strong>The highest EI was found for azathioprine, older antiepileptics, and minocycline. In contrast, many widely used drugs are rare causes of DILI. These findings may help clinicians better weigh potential benefits of medications against hepatotoxicity risk.</p>","PeriodicalId":11382,"journal":{"name":"Drug Safety","volume":" ","pages":"151-160"},"PeriodicalIF":4.0,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11785493/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142343748","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":"Fracture-Related Safety Reporting of JAK Inhibitors: An Analysis from the WHO Global VigiBase.","authors":"Adrian Martinez de la Torre, Andreas Bech Clausen, Andrea M Burden, Stefan Weiler","doi":"10.1007/s40264-024-01490-w","DOIUrl":"10.1007/s40264-024-01490-w","url":null,"abstract":"<p><strong>Introduction: </strong>The Janus kinase (JAK) inhibitors are treatment options for autoimmune diseases. Numerous safety concerns have been raised. The European Medicines Agency updated the product information of tofacitinib to include the risk of fractures-but not for other JAK inhibitors. We conducted a global pharmacovigilance analysis of previously investigated JAK inhibitors to investigate a potential class effect.</p><p><strong>Methods: </strong>Individual case safety reports (ICSRs) for all licensed JAK inhibitors were identified from the global WHO pharmacovigilance database. The primary outcome of interest was a bone fracture. Disproportionality analyses using reporting odds ratios (RORs) were conducted.</p><p><strong>Results: </strong>We identified 122,037 ICSRs for tofacitinib, 27,786 ICSRs for upadacitinib, 14,616 ICSRs for baricitinib, 830 for filgotinib, and 350 for abrocitinib. Among the ICSRs, we identified 2198 (1.8%), 634 (2.3%), and 144 (1.0%) reports, where a bone fracture was reported for tofacitinib, upadacitinib, and baricitinib, respectively. Few reports were available for the newest drugs filgotinib (10) and abrocitinib (1). JAK inhibitors were associated with increased reporting for fracture: tofacitinib (ROR 3.34, 95% confidence interval [CI] 3.20-3.48), upadacitinib (ROR 4.23, 95% CI 3.80-4.48), baricitinib (ROR 1.80, 95% CI 1.52-2.11) and filgotinib (ROR 2.24, 95% CI 1.11-3.94). Patients with bone fractures were more often female, older and had a higher number of co-reported medications. They were more likely to use glucocorticoids, opioids, and bisphosphonates.</p><p><strong>Conclusion: </strong>The results from this pharmacovigilance analysis, based on a spontaneous reporting database associated with inherent limitations, suggest a potential risk of fractures with JAK inhibitors, indicating that a class effect cannot be ruled out.</p>","PeriodicalId":11382,"journal":{"name":"Drug Safety","volume":" ","pages":"191-201"},"PeriodicalIF":4.0,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11785614/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142738682","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}