Expert Opinion on Drug Safety最新文献

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.

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.

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.

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.

Background: Amiodarone is used to treat cardiac arrhythmias but carries a risk of pulmonary toxicity. Despite this well-known side effect, there is currently no large descriptive case series studying amiodarone-induced pulmonary toxicity.

Methods: The reporting odds ratio (ROR) was utilized to quantify signals of amiodarone-related pulmonary adverse events (AEs) from 2004 to 2023. Severity comparisons between serious and non-serious cases were conducted using the Mann-Whitney U test or chi-square (χ2) test, and signal prioritization was achieved through rating scales.

Results: A total of 4896 cases of amiodarone-related pulmonary AEs were found, and 56 signals were detected. 27 AEs were classified as serious adverse reactions, and 21 AEs were identified as new and unexpected signals. Even when stratified by age, weight, sex, and reporter type, the association between amiodarone and pulmonary diseases persisted. Seven strong clinical priority signals were defined. The median time to onset (TTO) for strong, moderate, and weak clinical priority signals was 221, 126, and 227 days, respectively. All disproportional signals exhibited an early failure-type pattern.

Conclusion: Our study offers a deeper and broader understanding of the pulmonary safety profile of amiodarone, which will aid healthcare professionals in mitigating the risk of pulmonary adverse events in clinical practice.

Introduction: Multiple sclerosis (MS) is a chronic, immune-mediated disease of the central nervous system, characterized by relapses or progressive neurological decline. Over recent decades, high-efficacy immunosuppressive therapies have dramatically reduced relapse rates and curtailed new MRI lesion activity in MS, but also raise safety concerns regarding infections, malignancy, and other serious adverse events.

Areas covered: This review discusses immunosuppressants in MS, from older cytotoxic agents (azathioprine, cyclophosphamide, mitoxantrone) to newer therapies (cladribine, alemtuzumab, and anti-CD20 monoclonal antibodies). Key efficacy data are summarized, alongside risks of hematologic, hepatic, and autoimmune toxicities. Emerging evidence on malignancy risk is highlighted, including therapy-related acute leukemias (mitoxantrone), urothelial tumors (cyclophosphamide), and potential neoplasms linked to newer agents. Strategies for patient selection, screening, and long-term vigilance are examined to balance high-efficacy disease control with acceptable safety margins.

Expert opinion: Immunosuppressants remain vital for certain MS phenotypes, especially those with highly active or refractory disease. Although novel agents offer more selective mechanisms, they still pose notable risks demanding careful monitoring and individualized care. Ongoing research, including predictive biomarkers and post-marketing surveillance, will refine patient selection and mitigate adverse events. With judicious use and robust safety protocols, clinicians can achieve durable disease control while minimizing long-term toxicities.

Background: The sodium-dependent glucose transporters 2 inhibitors (SGLT-2i) is associated with body weight loss but the composition of the losing weight remains unclear.

Research design and methods: Disproportionality analyses, including the reporting odds ratio (ROR), the proportional reporting ratio (PRR), the Bayesian confidence propagation neural network (BCPNN), and the multi- item gamma Poisson shrinker (MGPS) algorithms, were employed to quantify the signals of SGLT-2i-associated musculoskeletal and connective tissue disorders AEs.

Results: The search retrieved a total of 3,206 cases of musculoskeletal and connective tissue disorder-related AEs during the reporting period. This included 1,061 cases for Canagliflozin, 1,052 cases for Dapagliflozin, 1,074 cases for Empagliflozin, and 19 cases for Ertugliflozin. Fifteen preferred terms (PTs) with significant disproportionality were retained. No musculoskeletal and connective tissue system-related AE signals were reported for Ertugliflozin. We identified a risk of muscle necrosis with Canagliflozin use, a risk of sarcopenia with Dapagliflozin use, and a chance of muscle atrophy with Dapagliflozin and Empagliflozin prescriptions. Most cases occurred within the first month after SGLT-2i initiation, and AEs can persist beyond 360 days of use.

Conclusions: Our study identified potential new musculoskeletal and connective tissue disorder-related AE signals associated with SGLT-2 inhibitors.

Background: Multidrug-resistant (MDR) infections pose a global public health crisis with significant mortality and economic burdens. Combination of polymyxins and vancomycin has shown effectiveness against MDR infections. However, their combined nephrotoxicity complicates clinical use. Given these concerns, we conducted a pharmacovigilance analysis using the FDA Adverse Event Reporting System (FAERS) to assess the nephrotoxicity of combinations of polymyxins and vancomycin compared to monotherapy.

Research design and methods: In this retrospective study, data from FAERS reports (2012 Q4 to 2023 Q2) were deduplicated and analyzed for adverse events (AEs) related to vancomycin, polymyxin B, and colistin. Disproportionality analyses were performed to evaluate the association between drugs and nephrotoxicity.

Results: A total of 9,796,784 adverse event reports, including 73,009 reports associated with nephrotoxicity, were included. All three drugs showed significant associations with nephrotoxicity. In combination therapy, polymyxin B-vancomycin exhibited a stronger association with nephrotoxicity compared to monotherapy, whereas colistin-vancomycin demonstrated a lower association with nephrotoxicity than colistin monotherapy.

Conclusions: This study found that combining vancomycin with colistin alleviated colistin-induced nephrotoxicity, while combining vancomycin with polymyxin B worsened polymyxin B-induced nephrotoxicity.

Background: This study aimed to analyze the risk signals of iodinated and gadolinium-based contrast media associated with anaphylaxis.

Research design and methods: Data from the United States Food and Drug Administration Adverse Event Reporting System (FAERS) were retrospectively reviewed from January 2004 to September 2022. Disproportionality and Bayesian analyses were used in data mining to screen for suspected anaphylaxis using contrast media.

Results: A total of 1240 reports of anaphylaxis associated with contrast media were identified (464 men, 37.4%). The average age of anaphylaxis associated with iodinated contrast media (ICM) and gadolinium-based contrast media (GBCM) was 56.8 ± 17.2 and 50.9 ± 18.0 years old, respectively (p < .001). Among ICM, iopamidol showed the highest reporting odds ratio (ROR) (29.0), and amidotrizoate showed the lowest ROR (7.4). Among low-osmolality ICM, iopamidol had the highest ROR (29.0), and iopromide had the lowest ROR (8.8). Among the macrocyclic agents, gadoteridol had the highest ROR (37.3), while gadoterate meglumine had the lowest (10.4). Among the linear agents, gadobenate dimeglumine had the highest ROR (28.8), and gadodiamide had the lowest (1.4). The mortality rate in ICM was significantly higher than that in GBCM (p < 0.001).

Conclusions: This study provides clinicians and pharmacists evidence for risk signals of anaphylactic reactions among contrast agents.