Expert Opinion on Drug Safety最新文献

Objective: This study evaluates the risk of ocular adverse events (AEs) associated with glucagon-like peptide-1 receptor agonists (GLP-1 RAs) using data from the FDA Adverse Event Reporting System (FAERS) and network pharmacology methods.

Methods: FAERS data from 2004 to 2024 were analyzed for ocular AEs linked to GLP-1 RA treatments. Disproportionality analysis (Reporting Odds Ratio, ROR) was used to identify signals, and a drug-gene interaction network explored potential mechanisms.

Results: Among 17,785,793 FAERS reports, semaglutide and lixisenatide were significantly associated with ocular AEs, with RORs of 1.25 (95% CI, 1.20-1.31) and 1.96 (95% CI, 1.70-2.27), respectively. Commonly reported AEs included blurred vision, visual impairment, and diabetic retinopathy, with some AEs occurring as early as 10 days after treatment initiation. Gene enrichment analysis highlighted potential links between GLP-1-related genes and ocular AEs.

Conclusion: The widespread use of GLP-1 RAs has raised concerns regarding their ophthalmic safety. This study contributes new evidence from real-world data, suggesting that semaglutide and lixisenatide are associated with significant risks of ocular AEs. Further experimental studies are warranted to elucidate the underlying mechanisms and confirm these associations.

Background: Aromatase inhibitors (AIs) are commonly used to treat postmenopausal hormone receptor positive breast cancer, but there is currently a lack of comprehensive safety reports on AIs in large-scale cohorts.

Research design and methods: We conducted a retrospective pharmacovigilance survey based on the FDA Adverse Event Reporting System, retrieving relevant reports from the 2004 to the 2023, aiming to conduct a comprehensive comparative analysis of adverse reactions associated with AIs. In addition, we elucidated the potential toxicological mechanisms of AIs related adverse events through functional enrichment analysis.

Results: A total of 7,933 adverse event reports related to AIs were collected, and there were 642 positive signals at the preferred term level. The top three signal intensities for anastrozole are: antiphospholipid syndrome, plantar fasciitis and autoimmune pancreatitis. The top three signal intensities for letrozole are: androgenetic alopecia and myosclerosis, pneumonic herpes virus. The top three signal intensities for exemestane are: infection reactivation, thyroxine free decreased and dilatation atrial. In terms of onset time, letrozole has the earliest onset time overall, followed by exemestane, and finally anastrozole.

Conclusions: Our research corroborates the typical adverse events linked to AIs while highlighting potential safety concerns in their real-world clinical application.

Background: Nirmatrelvir/ritonavir, commonly known as Paxlovid, is one of the main drugs used to treat COVID-19. Neurological disorders are among the adverse drug reactions (ADRs) linked to Paxlovid, yet comprehensive data-mining studies based on real-world neurological adverse events induced by Paxlovid are lacking.

Methods: It is an observational study, to reduce the risk of bias affected by COVID-19 disease, our study included only patients with COVID-19 disease. In this case, disproportionate analysis is performed using the Report Odds Ratio (ROR) and its 95% Confidence Interval (CI).

Results: We screened and compared all medications associated with COVID-19 (N = 439) and found that 22 of these were linked to neurological adverse reactions. Paxlovid was associated with a threefold greater number of neurological adverse events compared to all other drugs combined (N = 11,792), with a strong signal value (ROR = 2.27).

Conclusions: Compared to all other COVID-19-related drugs, Paxlovid has the highest number and stronger signal value for neurologic-related adverse reactions. Clinicians should pay special attention to female patients taking Paxlovid within the first 30 days, monitoring for symptoms such as dysgeusia, ageusia, headache, and anosmia. In addition, headache and anosmia are not uncommon occurrences as mentioned in the instructions and should be noted.

Background: Lapatinib, an FDA-approved tyrosine kinase inhibitor, treats HER2+ advanced/metastatic breast cancer. This study comprehensively analyzed its adverse reaction profile using FDA Adverse Event Reporting System (FAERS) to guide clinical use.

Research design and methods: Adverse event (AE) reports for lapatinib from the second quarter of 2007 to the second quarter of 2024 in FAERS were analyzed using Reporting Odds Ratio (ROR), Proportional Reporting Ratio (PRR), Multi-item Gamma Poisson Shrinkage (MGPS) and Bayesian Confidence Propagation Neural Network (BCPNN) to identify AE signals.

Results: Among 8300 AE reports, females (91.47%) and ages 40-59.9 (33.71%) were predominant. 20 system organ classifications (SOCs) were affected, with gastrointestinal disorders (ROR = 3.46) and skin disorders (ROR = 2.47) most significant. Based on the PT level, a total of 111 PTs were analyzed that met the four algorithms, including typical AEs such as diarrhea (n = 3410), vomiting (n = 856), and rash (n = 856), as well as some rare AEs that were not prompted by the drug inserts, such as neutropenia (n = 252), pericardial effusion (n = 43), lymphedema (n = 20). The majority of lapatinib-associated AEs had onset within 30 days (51%).

Conclusions: Lapatinib has a generally favorable safety profile, but gastrointestinal toxicity and dermatotoxicity require close monitoring to prevent serious AEs.

Background: Risk management in oncology is critical due to toxicity, narrow therapeutic windows, and strict dosing schedules. This study analyzed post-authorization studies from the HMA-EMA Real-World Data Catalogues evaluating the effectiveness of risk minimization measures (RMM) for oncology medicines.

Research design and methods: We reviewed all RMM effectiveness studies registered in the HMA-EMA RWD Catalogues until February 2024, focusing on medicines classified under ATC codes 'L' and 'V10' for oncological conditions. Data from protocols and reports were analyzed, including study design, population, objectives, RMM types, process and outcomes indicators and reported effectiveness.

Results: Out of 1,280 records, 21 studies met the inclusion criteria. Most studies (81%) were cross-sectional surveys, 57% targeted healthcare professionals, and 86% used primary data. Additional RMMs were evaluated in 81% of studies. Process indicators were assessed in nearly all studies, but only 5% included outcome indicators. Of the 15 studies with available results, 60% were deemed effective, 27% inconclusive, and 13% ineffective by the sponsors.

Conclusions: Future studies should set success thresholds in advance, use a dual evidence approach to measure outcomes, and consider new methods to increase participant numbers. Feasibility assessments prior to conducting studies are essential for achieving meaningful objectives in oncology risk management.

Background: Amivantamab stands as the pioneering bispecific antibody that targets both EGFR and MET, utilized in the treatment of locally advanced or metastatic non-small cell lung cancer (NSCLC) harboring EGFR ex20ins mutations. Nevertheless, a thorough assessment of its safety characteristics in the real-world remains unknown.

Research design and methods: The adverse event (AE) reports were collected through a search of the FDA Adverse Event Reporting System (FAERS) database spanning from 2019 Q1 to 2024 Q1, and then disproportionality analysis was utilized.

Results: Totally, 9,252,269 AE reports were obtained from the FAERS database, with 893 reports of amivantamab classified as primary suspect AEs. Amivantamab-related AEs were distributed in 23 organ systems, and 87 significant preferred terms (PTs) met the reporting odds ratio criteria. Novel significant AEs were detected, and the median time to onset of amivantamab-associated AEs was 43 days. In subgroup analysis, a higher proportion of patients who were male, over 65 years, and with pneumonitis or pneumonia were reported in the death cases. We also found that AEs may vary between intravenous and subcutaneous administration.

Conclusions: This investigation offered novel prospects for monitoring and addressing undesirable medication effects associated with amivantamab, which might improve the clinical medication safety.

Objective: To gain an improved comprehension of inclisiran safety in real-world settings by data mining from FAERS.

Methods: Data were gathered between 1 December 2020 and 31 December 2023. The Medical Dictionary for Regulatory Activities (MedDRA) corresponding preferred term (PT) and system organ class (SOC) were used to categorize adverse medication reactions in AE reports (AERs). By using reported odds ratio (ROR) method, positive signals were identified.

Results: There were 2,652 reports of inclisiran, and 150 of those AEs had significant disproportionality. Among the 44 PTs with moderate clinical priority, 35 PTs were discovered on the medicine label, including 12 IMEs and 2 DMEs. Of note, 9 PTs were unanticipated AEs that were not discovered in the medication label or reported clinical studies, such as movement disorder (ROR: 3.05; 95%CI: 1.73,5.37), aphonia (ROR: 3.77; 95%CI: 1.79,7.91), and pulmonary congestion (ROR: 3.47; 95%CI: 1.44,8.34). Inclisiran was found to be related to 12 serious AEs. The median TTO of 1896 cases was 13.5 (IQR 0-100) days.

Conclusion: We identified not only known AEs, but also new AE signals such as movement disorder. However, signals does not reveal actual risk, prospective clinical trials are still required to verify their causal connection.

Background: Lamotrigine (LTG), a medication frequently prescribed for epilepsy. Despite its widespread use, there remains a lack of clarity regarding the drug's safety profile when used over extended periods in large patient populations. This study evaluated the safety profile of LTG using the FDA Adverse Event Reporting System (FAERS), aiming to enhance clinical decision-making.

Research design and methods: We used disproportionate analyses, including the reporting odds ratio (ROR), proportional reporting ratio (PRR), Bayesian confidence propagation neural network (BCPNN), and empirical Bayes geometric mean (EBGM), to identify signals of adverse reactions associated with LTG.

Results: A total of 187,024 records were reported, involving 905 adverse drug event (ADE) signals across 27 system organs classes (SOCs). We detected several known adverse event (AE) signals from the clinical trial phase, including seizures, rash, Stevens-Johnson syndrome (SJS), toxic epidermal necrolysis (TEN), and drug reaction with eosinophilia and systemic symptoms (DRESS). Additionally, we uncovered several unforeseen and significant adverse effects that were not documented in the medication's prescribing information, encompassing suicides, atrial septal defects, Brugada syndrome, and signals associated with aortic stenosis.

Conclusions: Our analysis in the post-marketing setting reveals new AE signals associated with LTG, highlighting the need for ongoing risk surveillance.

Background: T-cell engagers (TCEs) are transformative immunotherapies with significant potential in treating hematologic malignancies and solid tumors. However, their real-world safety profiles remain inadequately characterized.

Research design and methods: Using the FDA Adverse Event Reporting System (FAERS) database (October 2019 - September 2024, 8,747,158 reports), we analyzed adverse events (AEs) associated with nine TCEs. Disproportionality analysis identified overreported AEs, with 11,963 unique reports analyzed after deduplication.

Results: Blinatumomab was the most reported TCE (n = 4,950), and Tarlatamab the least (n = 185). Predominant AEs included immune system disorders, particularly cytokine release syndrome (IC₀₂₅ range: 6.08-7.47). Drug-specific signals included reproductive system and breast disorders (IC₀₂₅: 2.74) and vascular disorders (IC₀₂₅: 2.25) with Tebentafusp, renal and urinary disorders with Epcoritamab (IC₀₂₅: 1.84), and eye disorders with Elranatamab (IC₀₂₅: 1.81). Novel AEs were also uncovered, including second malignant neoplasms, vasogenic cerebral edema with Mosunetuzumab (IC₀₂₅: 5.77, ROR₀₂₅: 56.29), and hydronephrosis with Epcoritamab (IC₀₂₅: 7.50, ROR₀₂₅: 180.70). Early-onset events (0.5-9.5 days) were linked to four TCEs, while delayed-onset events (>20 days) were linked to five others.

Conclusions: This study highlights diverse AE profiles of TCEs, providing insights for clinicians to optimize their safe use in practice.

Background: Edaravone is a novel free radical scavenger utilized to treat amyotrophic lateral sclerosis (ALS). However, long-term safety data remain limited.

Research design and methods: Adverse event reports related to edaravone from the second quarter of 2017 to the second quarter of 2024 were extracted from the US Food and Drug Administration (FDA) Adverse Event Reporting System database (FAERS). Disproportionality analysis was conducted utilizing the reporting odds ratio (ROR), proportional reporting ratio (PRR), Bayesian confidence propagation neural network (BCPNN), and multi-item gamma Poisson shrinker (MGPS) algorithms.

Results: A total of 3,149 adverse event reports related to edaravone were analyzed. The most common adverse reactions included systemic disorders and administration site reactions, nervous system disorders, respiratory system disorders, and surgical and medical procedures. New adverse reaction signals included disseminated intravascular coagulation, gastric fistula, sputum retention, excessive salivation, fractures, elevated cystatin C. The median onset time for adverse events was 43 days (interquartile range: 7-173 days).

Conclusion: This study confirmed previously reported adverse events and identified several new ones associated with edaravone. These findings provide valuable insights for optimizing ALS patient management and highlight the need for further research into the mechanisms of these adverse reactions.