Expert Opinion on Drug Safety最新文献

Introduction: Vanishing bile duct syndrome (VBDS) is a potentially fatal adverse reaction triggered by certain medications. The association between nonsteroidal anti-inflammatory drugs (NSAIDs) and VBDS is based on case reports. We explored the reporting prevalence and evaluated the clinical features of NSAID-related VBDS.

Research design and methods: Adverse event reports of VBDS associated with NSAIDs from 2004 to 2023 in the FAERS database were retrieved, and disproportionality analyses were conducted to detect risk signals. Case reports from 2000 to 2023 on NSAID-induced VBDS were retrieved for retrospective analysis.

Results: We obtained 87 VBDS reports from the FAERS database. Ibuprofen had the greatest proportion of VBDS (63.2%), while loxoprofen had the highest positive signal value. Sixteen case reports showed evidence of VBDS, with 37.5% of children. The median age was 29 years; typical initial symptoms included rash (60.0%), jaundice (53.3%), fatigue/asthenia (33.3%), and SJS/TEN (53.3%). The median onset time of VBDS was 4 weeks. All cases had abnormal liver function tests, with the median level of TBIL being 20.0 mg/dl. The overall prognosis is poor, with 50% of patients achieving clinical remission.

Conclusion: Four NSAID agents had significant reporting associations with VBDS. Prescribers should be more aware of this risk and identify signs/symptoms earlier.

Background: Myocarditis is a rare but potentially life-threatening inflammation of the heart muscle that can be caused by various drugs. This study aimed to comprehensively evaluate the risk of drug-induced myocarditis using data from the FDA Adverse Event Reporting System (FAERS) database.

Methods: We queried the FAERS database for reports of myocarditis from Q1 2004 to Q4 2023. The reporting odds ratio (ROR) and proportional reporting ratio (PRR) were calculated to detect disproportionality signals for drugs associated with myocarditis.

Results: A total of 8,212 myocarditis-related reports were identified in the FAERS database. The most frequently reported drugs were clozapine (N = 1269), followed by nivolumab (N = 621), pembrolizumab (N = 358), mesalazine (252), and olanzapine (N = 191). Disproportionality analysis revealed strong signals for the top 50 drugs, including mesalazine (ROR 48.01, 95% CI 42.29-54.49), cemiplimab (ROR 38.84, 95% CI 26.71-56.47), clozapine (ROR 35.21, 95% CI 33.13-37.39), nivolumab (ROR 23.21, 95% CI 21.38-25.2), atezolizumab (ROR 20.75, 95% CI 17.91-24.05) and pembrolizumab (ROR 19.90, 95% CI 17.89-22.13).

Conclusions: Our findings suggest a potential risk of drug-induced myocarditis associated with various medications. Close monitoring for signs and symptoms of myocarditis is crucial, especially in patients with risk factors or those receiving these drugs. Further investigations are warranted to establish causality and identify risk factors.

Introduction: Carbamazepine (CBZ) is a commonly used antiseizures medications (ASM), but its adverse drug reactions (ADRs) can impact the successful management of epilepsy. There are currently limited systematic studies on ADRs related to CBZ, necessitating further investigation.

Areas covered: Using the FDA Adverse Event Reporting System (FAERS) database , we extracted reports where CBZ was the primary suspect, conducting subgroup analyses stratified by sex and age. Four risk signal detection methods ROR, PRR, BCPNN, and EGBM were employed to systematically analyze the ADRs associated with CBZ.

Expert opinion: In the epilepsy population, ADRs related to CBZ often involve examinations, hereditary disorders, and infections. Subgroup analysis showed differences in ADR signals among male, female, elderly, and young patients. Human Herpesvirus 6 Infection and Dermatitis Exfoliative were consistent CBZ-induced ADRs, unaffected by age or sex. The study also identified previously overlooked ADRs such as bone metabolism abnormalities, ocular toxicity, and ototoxicity. Many ADRs linked to CBZ remain underreported. It is crucial to enhance monitoring and information dissemination about CBZ use in epileptic patients. Adjusting medication regimens for high-risk individuals, potentially incorporating acupuncture, traditional Chinese medicine, or alternative anti-seizure medications, should be considered when necessary.

Background: CAR-T-associated neurotoxicity is extremely frequent with highly variable clinical presentation.

Research design and methods: Disproportionality analysis was conducted leveraging the FDA Adverse Event Reporting System (FAERS), covering the period from 1 January 2017, through 31 March 2023. The reporting odds ratio (ROR) and the information component (IC) were utilized to assess the adverse signals in total/individual CAR-T product. The lower limit of the ROR and IC 95% confidence interval (ROR₀₂₅ and IC₀₂₅) both exceeding threshold value (1 and 0, respectively) was considered a significant signal.

Results: Of the 60, 730 records associated with CAR-T, 11, 037 (18.17%) pertained to neurological events. Tisagenlecleucel exhibited the highest percentage of death (38.02%) and life-threatening (12.90%) outcomes. Notably, it also displayed the broadest distribution of neurotoxicity. Additionally, distinct adverse signals unique to individual CAR-T products were identified. For instance, paraparesis, cerebral hemorrhage, impaired pupillary reflex, Guillain-Barre syndrome, brain death following tisagenlecleucel; dysarthria, orthostatic hypotension, and spinal cord edema after axicabtagene; parkinsonism, Bell's palsy, and cranial nerve paralysis post ciltacabtagene.

Conclusions: Axicabtagene ciloleucel, tisagenlecleucel, brexucabtagene autoleucel, lisocabtagene maraleucel, idecabtagene vicleucel, and ciltacabtagene autoleucel exhibited increased odds of neurotoxicity, with some discrepancies in their characteristics, profiles, and severity.

Background: The aim of this study was to explore the risk of severe cutaneous adverse reactions (SCARs) caused by different antifungal drugs in the real world.

Methods: We extracted the data from the FDA Adverse Event Reporting System (FAERS) from January 2004 to December 2022 and performed disproportionality analyses to characterize the signal differences of antifungal agents-related SCARs.

Results: A total of 952 antifungals-related SCARs were identified. Antifungal drugs-related SCARs were more common in the 18-64 age group than other groups, and five agents were detected significant SCAR signals in this age group. Among these antifungals, fluconazole had the strongest associations with the SCARs, and showed significant SCAR signals at all age stages. Six antifungals showed a significant association with SCARs under disproportionality. The reporting odds ratios (RORs) and the 95% confidence intervals (95% CI) for six antifungals were as follows: fluconazole (9.50, 8.62-10.47), caspofungin (8.92, 7.29-10.91), itraconazole (3.48, 2.78-4.35), amphotericin B (2.73, 2.20-3.39), micafungin (2.62, 1.85-3.71) and voriconazole (2.50, 2.12-2.94).

Conclusions: The data mining of FAERS demonstrated that antifungal drugs were significantly associated with SCARs, which reminded clinicians to continue monitoring patients who are at risk of developing SCARs with the use of these drugs.

Introduction: Studies assessing COVID-19 vaccine effectiveness have generally categorized individuals into 'vaccinated' and 'unvaccinated' groups. Long-term safety studies are sparse and have usually compared adverse events with background rates. Studies on timing of COVID-19 vaccination as a determinant of long COVID have provided variable results, while there is scarce data on timing of vaccination as a determinant of adverse events.

Areas covered: We discuss some of our observations as well as the global evidence on the timing of COVID-19 vaccination as a determinant of long-COVID and adverse events. This special report is hypothesis-generating and aims to propose a conceptual framework and not establish causality.

Expert opinion: We propose an alternative classification strategy for COVID-19 vaccinees, with special emphasis on individuals who received any dose of vaccination after recovering from natural COVID-19, i.e. the 'vaccine-after-COVID' (VAC) group. These individuals should be followed up for an extended period through multicentric and database studies. This may help in understanding the long-term safety of COVID-19 vaccines and the natural course of long COVID. Immunological characteristics of this group should also be scrutinized. The evidence gained might be useful in planning vaccination policies in the event of future pandemics.

Background: This study aimed to provide an overview of gastrointestinal (GI) adverse events associated with immune checkpoint inhibitors (ICIs) using two pharmacovigilance databases, EudraVigilance and VigiAccess.

Research design and methods: Data was collected from the date of ICI's marketing authorization until 30 November 2023. Reporting odds ratio (ROR) was used as a measure of ADR reporting disproportionality for signal detection.

Results: Overall, across both databases, EudraVigilance and VigiAccess, a total of 76,606 ADR reports were analyzed. In EudraVigilance, colitis (12,581) and diarrhea (12,108) were the most reported GI adverse events, with similar findings in VigiAccess. Furthermore, in both databases, the most ADR reports were associated with nivolumab and pembrolizumab. Durvalumab (ROR: 3.96, 95%CI :3.65-4.28), ipilimumab (ROR: 1.95, 95%CI: 1.89-2.01), nivolumab (ROR: 1.05, 95%CI: 1.02-1.07), and atezolizumab (ROR: 1.04, 95%CI: 1.01-1.07) demonstrated higher risks of GI events compared to other ICIs. EudraVigilance analysis identified dysphagia, ascites, hematochezia, and gastroesophageal reflux disease as potential signals associated with ICI therapy. Majority of ADR reports (87.2%) comprised serious GI adverse events, a portion of which was associated with fatal outcomes (14.5%). Atezolizumab (14.9%) and pembrolizumab (11.9%) were linked to a higher incidence of fatal outcomes compared to other ICIs.

Conclusion: The differential risk profiles of ICIs-associated-GI adverse events underscore the importance of personalized therapy in oncology.

Introduction: Abatacept, a biological disease-modifying antirheumatic drug(bDMARD), has demonstrated unique and effective therapeutic properties for rheumatoid arthritis (RA).

Areas covered: This review offers an in-depth examination of the mechanism by which abatacept exerts its effects in RA treatment and assesses its efficacy and safety based on a range of studies. We conducted a comprehensive search of PubMed, Embase databases, Web of Science, the Cochrane Library, MEDLINE, Wanfang Data, and CNKI from the time the databases were created until 30 July 2024.

Expert opinion: By modulating the CD28 and CD80/CD86 costimulatory signaling pathways, abatacept is instrumental in regulating immune cells and cytokines implicated in the pathogenesis RA. Longitudinal studies have highlighted its capacity to mitigate disease advancement and maintain joint functionality. The most frequently reported adverse effects associated with abatacept are headache, nausea, and upper respiratory tract infections, which are typically self-resolving. The incidence of serious infections was not high, mainly various types of bacterial pneumonia. Comparative safety analyses of abatacept with other DMARDs yield encouraging results. As our understanding of the mechanism of action of abatacept improves, we may be able to better identify appropriate biologic therapies and advanced combination therapies for RA patients and ultimately improve patient outcomes.

Objective: To investigate the association between levetiracetam and severe cutaneous adverse reactions (SCARs) using data from the FDA Adverse Event Reporting System (FAERS).

Methods: Disproportionality analysis was performed using the Reporting Odds Ratio (ROR) and Information Component (IC) methods. Patient demographics, clinical outcomes, time to onset, and concomitant medication data were examined.

Results: A total of 1,188 SCAR cases with levetiracetam as the primary suspect were analyzed through disproportionality analysis. Female patients comprised 45.96% of cases, with 50.42% aged between 18 and 65 years. The analysis indicated a significant association with SCARs, showing an ROR of 4.47 and an IC of 2.14. The most common SCAR was Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS), occurring in 540 cases. The median time to onset for SCARs was 16 days, with DRESS having a longer median of 20 days, while Acute Generalized Exanthematous Pustulosis (AGEP) had a shorter median of 3 days. Concomitant medications, including phenytoin, valproate, and aspirin, were common, with some drugs indicating an increased SCAR risk when used alongside levetiracetam.

Conclusion: The findings suggest a notable risk of SCARs associated with levetiracetam, with an emphasis on monitoring patients, particularly females and those on concomitant medications.