FDA Adverse Event Reporting System Research Articles

A Pharmacovigilance Study on Clozapine in the Food and Drug Administration Adverse Event Reporting System: A Regional Comparative Analysis.

This pharmacovigilance study evaluated the profile of clozapine-related adverse events by region using the Food and Drug Administration Adverse Event Reporting System (FAERS). We categorized each case into five regions (America, Europe/West Asia, Oceania, Asia, and Africa) based on the reporting country information in the FAERS database. The number of clozapine-related adverse events reported in each region was aggregated according to the preferred term (PT) and the Standardized Medical Dictionary for Regulatory Activities (MedDRA) Query (SMQ). A total of 101,872 clozapine-related adverse events were registered in the FAERS database. In America and Europe, leukocyte or neutrophil count abnormalities accounted for half of the top 10 PTs by relative reporting rate. However, Asia had higher relative reporting rates of pyrexia and salivary hypersecretion (13.91% and 10.85%, respectively). Regarding the SMQ, the relative reporting rates of infective pneumonia, convulsions, extrapyramidal syndrome, gastrointestinal obstruction, and hyperglycaemia/new onset diabetes mellitus were higher in Asia than in other regions (5.26%, 9.72%, 12.65%, 5.13%, and 8.26%, respectively), with significant differences even after adjusting for confounding factors using multivariate logistic regression analysis. Spontaneous reports of adverse events associated with clozapine show regional disparities, particularly in Asia, where concentration-dependent adverse events are more frequently reported. However, the spontaneous reporting system has several limitations, requiring further research for validation.

Trust but Verify: Lessons Learned for the Application of AI to Case-Based Clinical Decision-Making From Postmarketing Drug Safety Assessment at the US Food and Drug Administration.

Adverse drug reactions are a common cause of morbidity in health care. The US Food and Drug Administration (FDA) evaluates individual case safety reports of adverse events (AEs) after submission to the FDA Adverse Event Reporting System as part of its surveillance activities. Over the past decade, the FDA has explored the application of artificial intelligence (AI) to evaluate these reports to improve the efficiency and scientific rigor of the process. However, a gap remains between AI algorithm development and deployment. This viewpoint aims to describe the lessons learned from our experience and research needed to address both general issues in case-based reasoning using AI and specific needs for individual case safety report assessment. Beginning with the recognition that the trustworthiness of the AI algorithm is the main determinant of its acceptance by human experts, we apply the Diffusion of Innovations theory to help explain why certain algorithms for evaluating AEs at the FDA were accepted by safety reviewers and others were not. This analysis reveals that the process by which clinicians decide from case reports whether a drug is likely to cause an AE is not well defined beyond general principles. This makes the development of high performing, transparent, and explainable AI algorithms challenging, leading to a lack of trust by the safety reviewers. Even accounting for the introduction of large language models, the pharmacovigilance community needs an improved understanding of causal inference and of the cognitive framework for determining the causal relationship between a drug and an AE. We describe specific future research directions that underpin facilitating implementation and trust in AI for drug safety applications, including improved methods for measuring and controlling of algorithmic uncertainty, computational reproducibility, and clear articulation of a cognitive framework for causal inference in case-based reasoning.

Safety evaluation of ceftazidime/avibactam based on FAERS database.

To explore adverse event (AE) signals of Ceftazidime/avibactam (CZA) based on the FDA Adverse Event Reporting System (FAERS) database. AE reports primarily associated with CZA were retrieved from the FAERS database from the second quarter of 2015 to the second quarter of 2023. Signal detection was conducted using the reporting odds ratio (ROR), proportional reporting ratio (PRR), Bayesian Confidence Propagation Neural Network (BCPNN), and Multi-item Gamma Poisson Shrinker (MGPS) methods. A total of 750 AEs reports with CZA as the preferred suspected drug were obtained, identifying 66 preferred terms (PTs) involving 24 system organ classes (SOCs). Besides, the AEs already mentioned in the drug label, this study also revealed some new, clinically valuable potential AEsignals, such as Cholestasis (n = 14, ROR 29.39, PRR 29.15, IC 3.34, EBGM 29.11), Drug-induced liver injury (n = 8, ROR 9.05, PRR 9.01, IC 2.25, EBGM 9.01), Hepatocellular injury (n = 7, ROR 13.90, PRR 13.84, IC 2.41, EBGM 13.63), Haemolytic anaemia (n = 5, ROR 24.29, PRR 24.22, IC 2.42, EBGM 40.53), etc. Additionally, AE signals with higher intensity were identified, such as Hypernatraemia (n = 5, ROR 40.73, PRR 40.61, IC 2.31, EBGM 24.19), Toxic epidermal necrolysis (n = 4, ROR 11.58, PRR 11.55, IC 1.89, EBGM 11.54). Therefore, special vigilance for these potential AEs is warranted when using CZA clinically. This study highlights the potential AEs and risks associated with the clinical use of CZA, particularly the risks related to Cholestasis, Drug-induced liver injury, Haemolytic anaemia, Hypernatraemia, and Toxic epidermal necrolysis.

Adverse drug reactions in neonates: a brief analysis of the FDA adverse event reporting system.

Drug trials in neonates are scarce, and the neonates may consequently be at risk of adverse drug reactions (ADRs). Spontaneous ADR reporting is an important tool for expanding the knowledge on drug safety in neonates. This study explores the quality of current neonatal ADR reports and the ADR reports of the most common drugs used in neonatal departments. An observational cross-sectional study focused on neonates was conducted using data on spontaneous reports extracted from the U.S. Food and Drug Administration Adverse Events Reporting System (FAERS) from the third quarter of 2014 up to December 2022. Only the primary suspect drugs given to neonates or subjects aged <30 days were included in the analysis. Spontaneous reports from 13 million patients of all ages, totaling 50 million ADRs, were evaluated. Information regarding the age was missing in 40% of the reports, and data on 43,737 neonates with 948 different suspected drugs were identified and included in the analysis. We report the frequency of spontaneous ADR reports in the FAERS database for the ten most frequently administered drugs in neonatal intensive care units in the USA. Overall, neonatal ADRs are still underreported. The FAERS database in its current form discriminates insufficiently between prenatal and postnatal drug exposures. Hence, improved neonatal pharmacovigilance systems are urgently needed.

Post-marketing safety of lorlatinib: a real-world study based on the FDA adverse event reporting system.

Lorlatinib displays marked systemic and intracranial efficacy against anaplastic lymphoma kinase (ALK) positive non-small cell lung cancer (NSCLC). We aimed to establish the safety profile of lorlatinib based on the Food and Drug Administration Adverse Event Reporting System (FAERS). Reports from the FAERS between 2019 and 2023 were collected to conduct the disproportionality analysis. Reporting odds ratio (ROR) was employed to detect the potential adverse events (AEs) related to lorlatinib. The clinical characteristics, age and gender differences, time to onset of AEs were also investigated. A total of 2,941 AE reports were found to be associated with lorlatinib among the 8,818,870 AE reports obtained from the FAERS database. 167 lorlatinib-related AE signals were identified. The frequently reported AEs including hypercholesterolemia, oedema, and cognitive disorder were in line with those observed in clinical trials and drug instruction. However, AEs such as interstitial lung disease and AV block indicated in the drug label require further evaluation. More attention should be paid to the new potential unexpected AEs including pulmonary arterial hypertension and radiation necrosis. Furthermore, we examined the specific high-risk AEs of different ages and genders. In addition, majority of AEs occurred within the first 2months after lorlatinib initiation with a median onset time of 51days. Our study provides valuable insight into the post-marketing safety profile of lorlatinib, which can potentially benefit the rational and safe administration of lorlatinib in the clinic. Further prospective studies are needed to validate the associations between lorlatinib and the identified AEs.

Adverse events in different administration routes of semaglutide: a pharmacovigilance study based on the FDA adverse event reporting system.

With the continuously increasing incidence of type 2 diabetes, glucagon-like peptide-1 (GLP-1) receptor agonists, known for their dual benefits of effectively controlling blood glucose levels while also reducing weight and lowering cardiovascular disease risks, have been widely employed in the treatment of this condition. In recent years, semaglutide has garnered significant attention as the only injectable and orally administered glucagon-like peptide-1 receptor agonist (GLP-1RA). However, it is important to note that different routes of administration may lead to varying adverse events in patients. The aim of this study is to compare the adverse event profiles of semaglutide across different routes of administration by analyzing the adverse event reporting system of the U.S. Food and Drug Administration (FDA). The findings from this analysis will provide valuable insights for clinical practice and drug surveillance. Data was extracted from the U.S. Food and Drug Administration Adverse Event Reporting System (FAERS) database, specifically focusing on the period from the fourth quarter of 2017 to the fourth quarter of 2023. A comparative analysis was conducted using disproportionality analysis, reporting odds ratio (ROR), and stratified analysis methods to assess and compare the signals of adverse events (AE) and the time to onset of adverse reactions associated with different routes of administration of semaglutide from 2017 to 2023. A total of 22,287 adverse reaction records related to semaglutide were identified in the FAERS database. A comparative analysis was performed on 16,346 records of subcutaneous administration and 2,496 records of oral administration. Different routes of administration can lead to varying adverse reaction outcomes. Compared to oral administration, subcutaneous injection is more likely to result in adverse events related to the endocrine system. Oral administration is more likely to induce adverse events in the gastrointestinal system. Additionally, it significantly accelerates the onset of adverse reactions. The comparative analysis of all relevant results indicates that semaglutide can lead to different adverse reaction events depending on the route of administration. Furthermore, there are significant differences in the time of onset for these adverse reactions. Semaglutide exhibits variations in adverse reaction events and the time of onset across different routes of administration. Therefore, when selecting the route of administration for semaglutide, clinicians should consider the risk of adverse events and weigh them against the clinical benefits. Based on these considerations, appropriate guidance and recommendations can be provided to patients.

Long-term safety of lanthanum carbonate in the real word: a 19-year disproportionality analysis from the FDA Adverse Event Reporting System

Background Lanthanum carbonate is widely used to manage serum phosphate and calcium levels in end-stage kidney disease (ESKD) patients, yet comprehensive long-term safety data are lacking. This study leverages the FDA Adverse Event Reporting System (FAERS) to assess the extended safety profile of lanthanum carbonate. Research design and methods We analyzed FAERS data (2004-2022) to study the association between lanthanum carbonate and adverse events (AEs). Using MedDRA v25.0, we identified risk signals through System Organ Classes (SOCs) and Preferred Terms (PTs). Disproportionality analyses quantified lanthanum carbonate-associated AE signals. Results Among 3,284 reports, 2,466 were primary suspected AEs linked to lanthanum carbonate. Males reported AEs more frequently than females. Patients aged over 64 represented the majority. Median onset time for lanthanum carbonate-related AEs was 146 days. Gastrointestinal disorders were prevalent. We identified 16 new signals, including stress, abnormal hepatic function, cholelithiasis, bile duct stone, gastric cancer, and adenocarcinoma gastric. Stress was notable, particularly in male patients over 65 and those with lower weight. Conclusions This study affirms lanthanum carbonate’s long-term safety for reducing elevated blood phosphorus levels. While gastrointestinal disorders were common, attention must focus on emerging AEs, particularly stress, especially in elderly patients.

Analysis of Inclisiran in the US FDA adverse event reporting system (FAERS): a focus on overall patient population and Sex-specific Subgroups.

ABSTRACT Background our study aimed to identify inclisiran-related adverse events(AEs) for primary hypercholesterolemia and arteriosclerotic cardiovascular disease(ASCVD) from the US FDA Adverse Event Reporting System (FAERS) database, analyzing its links to AEs in the overall patient population and sex-specific subgroups to improve medication safety. Methods We analyzed inclisiran-related AEs signals by using statistical methods like Reporting Odds Ratio (ROR), Proportional Reporting Ratios (PRR), Bayesian Confidence Propagation Neural Network (BCPNN), and Multi-item Gamma-Poisson Shrinker (MGPS). Results Analyzing 2,400 AE reports with inclisiran as the primary suspected drug in the FAERS database, we identified 70 AE signals over 13 organ systems using the above four methods. Notable findings were strong signals for systemic diseases and various reactions at the site of administration (ROR 1.49, 95% CI 1.41-1.57), and Various musculoskeletal and connective tissue diseases (ROR 4.07, 95% CI 3.83-4.03) in overall and gender-specific populations. Myalgia, a new ADE signal not in the drug insert, was a top signal by intensity and frequency (ROR 14.76, 95% CI 12.84-16.98). Conclusion Our study revealed the strongest AE signals associated with inclisiran in both the overall population and gender subgroups, highlighting potential risks in clinical medication use and guiding balanced clinical decision-making.

Association between dual orexin receptor antagonists (DORAs) and suicidality: reports to the United States Food and Drug Administration Adverse Event Reporting System (FAERS)

ABSTRACT Background Package inserts for the FDA-approved dual orexin receptor antagonists (DORAs) suvorexant, lemborexant and daridorexant state that suicide risk should be monitored. It remains unknown whether suicidality is attributed to DORAs. We aim to evaluate suicidality associated with DORAs reported to the FDA Adverse Event Reporting System (FAERS). Methods The reporting odds ratio (ROR) was determined with trazodone as the control. Significant disproportionate reporting was determined when 95% confidence intervals (CIs) did not encompass 1.0. We used information components (ICs) to calculate the lower limit of the 95% CI (IC025). IC was significantly increased when the IC025 ≥0. Results Suvorexant (0.025 ROR), lemborexant (0.019 ROR) and daridorexant (0.002 ROR) were significantly associated with lower odds of reported completed suicides compared to trazodone (p < 0.05). There was no significantly increased RORs for the DORAs regarding suicidal ideation, depression suicidal, suicidal behavior and suicide attempts. Nonsignificant associations between all parameters of suicidality were observed for each DORA using IC025. Conclusion We did not find a significant association between any parameter of suicidality captured in the FAERS for each DORA. All persons treated for insomnia pharmacologically/non-pharmacologically should be evaluated for emergence/worsening of any suicidality aspect.

Comparison of safety of acetaminophen and ibuprofen in minors: based on the FAERS database

ABSTRACT Objective To investigate adverse events(ADEs) associated with the use of paracetamol and ibuprofen in people under 18 years of age. Background The use of NSAIDs reached a peak as a result of the spread of COVID-19 in previous years. Minors, as a special population, need to pay more attention to the use of corresponding drugs and the occurrence of adverse events (ADEs). Methods The population was divided into four age groups: infant group, preschool group, children group, and adolescent group. ADE report data of the two drugs were extracted from the FDA Adverse Event Reporting System(FAERS) from the first quarter of 2014 to the third quarter of 2022. The reporting odds ratio(ROR) method and the medicine and health products regulatory agency(MHRA) method were used for data mining and analysis. Results The two drugs mainly involved in injuries, poisoning and operational complications in the infant group, preschool group and adolescent group. The use of the two drugs in this population was primarily associated with injury, poisoning and surgical complications. The psychiatric disorders produced by the use of acetaminophen(12.6%) and ibuprofen(9.2%) in the adolescent group were significantly higher than those in the other age groups. The use of acetaminophen in the four age groups involved hepatobiliary disorders was more significantly (10.3%, 8.1%, 9.1%, 11.5%), while the use of ibuprofen was more obviously involved in renal and urinary disorders(5.0%, 6.2%, 9.6%, 7.1%). Conclusions The use of acetaminophen and ibuprofen in children of different age groups has different characteristics. Pediatric clinical pharmacists can provide medication monitoring to minimize ADEs based on these characteristics.

Safety assessment of dapagliflozin: Real-world adverse event analysis based on the FAERS database from 2012 to 2023

BackgroundDapagliflozin possesses the capacity to cure a wide range of diseases, however, there are many adverse events (AEs) that have not yet been acknowledged or recorded. AimSafety assessment of dapagliflozin based on the Food and Drug Administration Adverse Event Reporting System (FAERS) database, to explore differences between the reported AEs to provide a overview of the safety profile of dapagliflozin. MethodsWe extracted data from the United States FAERS database, including from the fourth quarter of 2012 to the third quarter of 2023. Reporting odds ratio (ROR), proportional reporting ratio (PRR), Bayesian confidence propagation neural network (BCPNN), and empirical Bayesian geometric average (EBGM) were used to evaluate the relationship between dapagliflozin and its associated AEs. ResultsA total of 13,593,946 case reports were gathered from the Food and Drug Administration Adverse Event Reporting System database for this investigation. Among these, there were 44,506 episodes of adverse events that were associated with dapagliflozin. Included in the analysis were 341 preferred words and 2 system organ classes that showed statistical significance according to all four methods simultaneously. The system organ classes encompassed illnesses related to metabolism and nutrition, as well as problems affecting the renal and urinary systems. PT levels were screened for adverse drug reaction signals including scrotal gangrene, scrotal cellulitis, perineal cellulitis, diabetic ketoacidosis, and pancreatitis. ConclusionThe majority of our findings aligned with the specification, however, certain novel indicators of AEs such as acute pancreatitis were not accounted for. The analysis of the AE signals may provide support for clinical monitoring and risk identification of dapagliflozin. Due to the inherent limitations of FAERS data, well-designed studies are required to demonstrate the safety of dapagliflozin.

Association of non-steroidal anti-inflammatory drug use with encephalopathy development: An analysis using the United States Food and Drug Administration Adverse Event Reporting System (FAERS) and Japanese Adverse Drug Event Report (JADER) databases.

Encephalopathy is the most severe complication of various common infections, including influenza and herpes, and it often results in death or severe neurological disability. The risk factors for viral encephalopathy include non-steroidal anti-inflammatory drug (NSAID) use; however, studies on NSAID-related encephalopathy are limited. In this study, we aimed to investigate the characteristics of NSAID-related encephalopathy. We investigated the incidence of NSAID-related encephalopathy using data from the United States Food and Drug Administration Adverse Event Reporting System (FAERS) and Japanese Adverse Drug Event Report (JADER) databases containing reports on spontaneous adverse effects (AEs) published by the Pharmaceuticals and Medical Devices Agency. We used these databases to detect AEs based on reported odds ratios. By separating suspicious drugs, concomitant drugs, and drug interactions involving NSAIDs, we investigated the relationship between encephalopathy pathology and AEs of NSAIDs. Significant encephalopathy signals were detected for loxoprofen and etodolac in the FAERS database and loxoprofen in the JADER database. In the JADER database, significant encephalopathy signals in loxoprofen-treated patients were detected in 70-79-year-old, ≥80-year-old, influenza viral infection, and herpes virus infection groups. Significant encephalopathy signals in patients with herpes virus infection were detected in the ≥80-year-old and loxoprofen-treated groups. Regarding the involvement of loxoprofen in the development of encephalopathy, the JADER database listed loxoprofen as a suspect drug, without indicating any concomitant drug interactions. In conclusion, our findings suggest that loxoprofen and etodolac may be associated with viral encephalopathy. Accordingly, prudence is recommended when using loxoprofen in older individuals with viral infections.

Risk assessment of cardiovascular adverse events with BTK inhibitors in hematological malignancies: Insights from FAERS.

12145 Background: Burton tyrosine Kinase inhibitors (BTKi) have revolutionized the care of chronic lymphocytic leukemia (CLL) and non-Hodgkin lymphomas (NHL) – including relapsed/refractory mantle cell, ABC diffuse large B cell lymphoma and and lymphoplasmacytic lymphoma. Ibrutinib was the first BTKi to be approved. The newer covalent BTKi include acalabrutinib and zanubrutinib, both of which are approved for frontline and relapsed CLL as well as relapsed NHL. All these agents have cardiovascular adverse events. We aimed to assess the pharmacovigilance (PV), reporting rate, severity, and reaction outcomes of different approved BTKi in the CLL as cancer reported to the United States Food and Drug Administration Adverse Event Reporting System (FAERS). Methods: We analyzed cardiovascular events in 86,370 patients on BTKi. Cardiovascular event reports were submitted to FAERS between 2004-2023 and analyzed using the AERS Mine framework. We compared these incidences within different BTKI. We divided cardiovascular events to three categories: cardiac arrythmia, major coronary or vascular event (MACE) and pericardial complication including effusion or hemorrhage. Our primary composite endpoint was the PV of cardiovascular events caused by BTKI. To mitigate confounding, BTKI were analyzed as mutually exclusive cohorts: Ibrutinib (n = 79,278), acalabrutinib (5200), and zanubrutinib (1354). Two-way ANOVA testing was done to evaluate for statistical significance across the different groups. Results: Across the 86,370 patients on BTKI, we identified 8500 reports of cardiovascular events – ibrutinib (10.15%), acalabrutinib (5.73%), and Zanubrutinib (4.72%). Arrythmia risk was higher with ibrutinib (6.6%) compared to acalabrutinib (3.12%) and zanubrutinib (2.29%). The major difference in the groups was driven by atrial fibrillation (5.1% vs 2.1% vs 1.8%). The MACE rate was 2.79% vs. 2.4% vs. 2%, and pericardial events were 0.72% vs. 0.21% vs. 0.44% in the ibrutinib, acalabrutinib, and zanubrutinib groups, respectively. All the AEs were to have statistical significance (p = 0.011) across all the BTKI as mentioned in table 1. Conclusions: We report the prevalence rate of BTKI-related cardiovascular events in a large cohort of patients. Ibrutinib has demonstrated a higher incidence of toxicity, especially in cardiac arrythmias, while smaller but significant differences exist in other toxicities, including major cardiovascular events and pericardial effusion or hemorrhage. Patient selection and toxicity monitoring are important aspects of the care of these patients, who stay on these therapies for indefinite periods. [Table: see text]

Risk assessment of myelosuppression with PARP inhibitors in prostate cancer: Insights from FAERS.

12144 Background: DNA damage repair defects are prevalent in 15% of Prostate cancer. FDA has approved four PARP inhibitors to be used for metastatic castration resistant prostate cancer (mCRPC). Based on the approvals, currently Olaparib, Niraparib, Rucaparib and Talazoparib have been approved alone or in combination with an Androgen receptor pathway inhibitor (ARPI). All these agents have myelosuppressive (MS) events . We aimed to assess the pharmacovigilance (PV), reporting rate, and reaction outcomes of different approved PARP inhibitors in the mCRPC setting reported to the United States Food and Drug Administration Adverse Event Reporting System (FAERS). Methods: We analyzed MS events in 2,137 patients on PARP inhibitors. MS event reports were submitted to FAERS between 2004-2023 and analyzed using the AERS Mine framework. MS incidences were analyzed within different PARP inhibitors utilized for prostate cancer. Our primary composite endpoint was the PV of MS caused by olaparib, rucaparib, niraparib and talazoparib for the treatment of mCRPC. PARP inhibitors were analyzed as mutually exclusive cohorts. Standard PV metrics were used to determine MS association with PARP inhibitors and two-way ANOVA testing was used to evaluate for statistical significance across the treatment groups. Results: 2,137 prostate cancer patients on PARP inhibitors were identified. MS events (n=677)– olaparib (227/831, 27.32%), rucaparib (n = 171/495, 34.55%), niraparib (63/111, 56.76%), and talazoparib (34/47, 72.34%). MS events were further categorized into five classes – anemia (n = 311, 45.94%), leukopenia (n = 123, 18.17%), thrombocytopenia (n = 107, 15.81%), pancytopenia (n = 102, 15.07%), and myelodysplastic syndrome (MDS) or Acute Myeloid Leukemia (AML, 34, 5.02%). Anemia rates across the four cohorts were identical (table). Leukopenia rates were highest in talazoparib cohort (27.66%). Thrombocytopenia rates were highest in niraparib cohort (24.32%). For pancytopenia, rates were highest in talazoparib 10.64%. MDS/AML rates were Talazoparib (2.13%), Olaparib (1.8%). The relative rates of MS events were significantly different across the PARP inhibitors (p &lt; 0.05, Table). Conclusions: This is the first study specific to prostate cancer analyzing the relative rates of MS events across different PARP inhibitors. Talazoparib exhibited the highest incidence of myelosuppression. This underscores the careful patient selection and vigilant monitoring needed in PARP inhibitors. Prompt recognition of myelosuppression is needed to optimize the safety and efficacy of PARP inhibitor therapies in prostate cancer. [Table: see text]

Dermatologic adverse events in EGFR-TKIs: A real-world analysis.

e20572 Background: Dermatologic adverse events (DAEs) affect a significant number of patients with non-small cell lung cancer (NSCLC) who are treated with epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs). While many DAEs have been identified during clinical trials and included in FDA drug labels, patients have raised concerns about experiencing unexpected DAEs. This study reviews the FDA Adverse Events Reporting System (FAERS) to identify DAEs in EGFR TKIs approved in NSCLC that are not included in drug labels. Methods: FAERS was queried for DAEs between 2003 – 2023 for osimertinib, afatinib, ertlotinib, gefitinib and mobocertinib. The reporting odds ratio (ROR) was calculated to compare DAEs between these EGFR-TKIs and all other drugs in the database. DAEs were considered statistically significant if the lower limit of the ROR 95% confidence interval (CI) was &gt; 1 and if there were ≥ 3 reported adverse reactions. Results: 67,480 adverse events were reported for the 5 EGFR-TKIs studied. DAEs constituted 30.3% (20,426) of all adverse event reports. We identified skin (skin fissures, eczema, lip swelling, and skin infection), nail (onychalgia and onychomadesis), and hair (abnormal hair growth and hair disorder) DAEs not previously included in EGFR-TKI drug labels. RORs with 95% CIs are summarized in the table. Conclusions: Real-world FAERS data complements clinical trial data in identifying specific DAEs affecting NSCLC patients treated with EGFR TKIs. Our findings highlight DAEs that were previously not described, aiding clinicians in educating patients about side effects and giving patients a more nuanced understanding of what to expect before undergoing treatment. [Table: see text]

Treatment-related adverse events of PD-1 versus PD-L1 inhibitors commonly used in lung cancer therapy: Analysis of real-world FAERS data.

e14598 Background: With the increasing utilization of immune checkpoint inhibitors (ICIs) in the dynamic landscape of cancer treatment, understanding immune-related adverse events (AEs) has become crucial for optimizing patient outcomes and therapeutic selection. In this study, we utilized the FDA Adverse Event Reporting System (FAERS) database to assess AEs reported with commonly used PD-1 and PD-L1 inhibitors in lung cancer therapy. Methods: We conducted a retrospective FAERS public database review to assess anti-PD-1 inhibitors (Pembrolizumab and Nivolumab) and anti-PD-L1 inhibitors (Atezolizumab and Durvalumab) reported AEs from January 2017 through September 30, 2023. We assessed disproportionality signals by calculating the reporting odds ratio (ROR) with a 95% confidence interval (CI). Significance was determined when the lower limit of the 95% CI exceeded 1. Results: In our analysis of 134,184 reported AEs, anti-PD-1 therapies had higher rates of cardiac AEs (ROR = 1.08; 95% CI: 1.03-1.14; P = 0.0015), vascular AEs (ROR = 1.23; 95% CI: 1.17-1.30; P &lt; 0.0001), respiratory AEs (ROR = 1.30; 95% CI: 1.25-1.34; P &lt; 0.0001), gastrointestinal AEs (ROR = 1.04; 95% CI: 1.01-1.08; P = 0.0117), hepatobiliary AEs (ROR = 1.12; 95% CI: 1.07-1.17; P &lt; 0.0001), and renal and urinary AEs (ROR = 1.06; 95% CI: 1.01-1.11; P = 0.0195) compared to anti-PD-L1 therapies. Conversely, anti-PD-L1 therapies had higher rates of endocrine AEs (ROR = 1.31; 95% CI: 1.25-1.38; P &lt; 0.0001), skin and subcutaneous tissue AEs (ROR = 1.43; 95% CI: 1.37-1.49; P &lt; 0.0001), and musculoskeletal and connective tissue AEs (ROR = 1.33; 95% CI: 1.26-1.39; P &lt; 0.0001) compared to anti-PD-1 therapies. Conclusions: Our study provides insights into the adverse event profiles of selected anti-PD-1 and anti-PD-L1 therapies in a real-world clinical setting. Further prospective studies are essential to enhance our understanding of the comparative safety profiles of these agents, guiding personalized treatment decisions and, ultimately, advancing patient outcomes.

Immune-related adverse events associated with nivolumab: Analysis of the FAERS database in the United States.

e24126 Background: To describe the risk of nivolumab adverse events (AEs) and to provide a reference for the safe clinical to use this drug. Methods: Nivolumab AE reports from January 2014 to December 2023 were collected from the FDA Adverse Event Reporting System, with a total of 133,12811 background patients (3,853,1848 occurrences of adverse events) included in the analysis, of which the number of patients in the target drug population was 60,625 (16,512 occurrences of adverse events). The number of patients in the target drug population was 60625 (161512 adverse events). Signals were detected using the Reporting Odds Ratio (ROR) method in conjunction with the Proportional Reporting Ratio (PRR), with signal judgment thresholds typically using a ≥ 3, and the lower limit of the 95% confidence interval for the ROR being greater than 1, The ROR and PRR (using a ≥ 3, and the lower limit of the 95% confidence interval for the ROR being greater than 1) were compared to the PRR. When ROR and PRR (using a ≥ 3, PRR ≥ 2 and chi-square ≥ 4 as thresholds) were used in combination, signal crossover between the two methods was defined as a positive risk signal. The preferred system organ classification (SOC) and preferred terminology (PT) of the current version of the MedDRA dictionary were used to classify AEs, and the top 30 PTs in terms of AE signal intensity were selected for analysis. Results: A total of 161,512 reports of AE with nivolumab as the first suspected drug were collected, involving 5174 PTs. A total of 995 positive PT signals were calculated using the combined ROR and PRR assay. The top 5 risk signals induced by nivolumab were immune-mediated small bowel colitis (ROR (95% CI) 114.42 (103.26-126.79), PRR (Chi-Square) 114.04 (40959.8)), pituitary gland inflammation (ROR (95% CI) PRR (Chi-Square) 88.60 ( 79.17-99.15)PRR(Chi-Square)88.37(26256.6)), fulminant type 1 diabetes mellitus (ROR(95% CI)213.73(183.24-249.30),PRR(Chi-Square)213.33(34295.5)) immune-mediated pneumonias (ROR(95% CI) 114.08 (99.42-130.89),PRR(Chi-Square) 113.87 (22764.4)), immune-mediated hepatitis (ROR(95% CI) 86.09 (75.08-98.71),PRR(Chi-Square) 85.94 (17262.8)).The top 5 SOCs were systemic diseases and various reactions at the site of administration in 25447 cases (15.76%), gastrointestinal disorders in 25447 cases(15.76%), gastrointestinal disorders 16,282 cases (10.08%), various types of injuries, poisoning and operational complications 12,510 cases (7.57%), respiratory, thoracic and mediastinal disorders 11,572 cases (7.16%), as well as benign, malignant, and tumors of undetermined nature (including cystic and polypoid) 10,486 cases (6.49%). Conclusions: The risk signal of autoimmune diseases caused by nivolumab is relatively strong, and it is recommended that clinicians should pay attention to the possible autoimmune diseases of various systems during the use of the drug.

Association of posterior reversible encephalopathy syndrome with proteasome inhibitors approved for multiple myeloma: Analysis of FAERS database.

e19515 Background: Proteasome inhibitors (PI) are a class of drugs that are used in the treatment of Multiple Myeloma. There are currently three PIs (Bortezomib, Carfilzomib, and Ixazomib) approved by FDA for this indication. Peripheral neuropathy has been described as one of their most common side effects but the association with another life-threatening neurological disorder, Posterior Reversible Encephalopathy Syndrome (PRES), remains poorly understood. Methods: We conducted a retrospective pharmacovigilance study using the FDA Adverse Event Reporting System database to analyze the risk of PRES associated with various Proteasome Inhibitors. We employed disproportionality signal analysis and calculated the reporting odds ratio with a 95% confidence interval. Results: A total of 79,450 adverse events were found within the FAERS database that were associated with the three FDA approved PIs. PRES accounted for 274 cases, of which 165 cases were in females and 71 cases in males. Majority of patients were adults, with 119 cases between 18-64 years of age, 88 cases above 65 years, and 50 cases with age not specified. Death was reported in 70 cases while 74 cases were marked as having life threatening illness, and 152 cases needed hospitalization. Bortezomib accounted for most cases (202 cases, ROR 6.03, 95% CI 5.3-7.1), followed by Carfilzomib (68 cases, ROR 7.2, 95% CI 5.7-9.1), and Ixazomib (9 cases, ROR 0.99, 95% CI 0.5-1.7). Conclusions: The study helps to shed light on the incidence, and hospital outcomes of PRES associated with various proteasome inhibitors. Significant safety signals were found for Bortezomib, and Carfilzomib. Females were almost 2.5 times more likely to develop PRES compared to males. These findings highlight the importance of keeping a high index of suspicion for PRES while evaluating patients on PIs who present with concerning neurological symptoms.

Immunosuppressant drug-associated skin cancer: A real-world pharmacovigilance database analysis.

e21575 Background: The association between immunosuppressant drugs and skin cancer has been frequently reported; however, the precise relationship remains uncertain. Skin cancer is among the most common cancers associated with long-term immunosuppressant drug use. The FDA Adverse Event Reporting System (FAERS) is a publicly available tool that collects reports of adverse events related to the use of certain drugs and biologic agents, thereby generating real-world data. Methods: The FAERS database was searched for skin cancer as an adverse event. Nine drugs belonging to different immunosuppressant classes were shortlisted. Reporting odds ratio (ROR) was used to measure disproportionality in reporting of adverse events for these drugs. Results: When skin cancer was analyzed as a percentage of all cancers reported as an adverse event for a particular drug,sirolimus had the highest percentage (30.11%) followed by infliximab (23.91%), azathioprine (23.69%), cyclosporine (19.71%), adalimumab (16.79%), mycophenolate (16.77%), etanercept (15.69%), tacrolimus (14.07%) and methotrexate (10.95%). Drugs with highest ROR for skin cancer included sirolimus (2.12, 1.88-2.39) followed by infliximab (1.68, 1.62-1.75) and azathioprine (1.54, 1.44-1.66). Drugs with lowest ROR for skin cancer included methotrexate (0.55, 0.52-0.57) followed by tacrolimus (0.78, 0.74-0.83) and etanercept (0.89, 0.85-0.93). Conclusions: Although all immunosuppressive drugs have been associated with an increased risk of developing skin cancer, it is advisable to exercise caution with prescribing sirolimus, infliximab and azathioprine in patients with preexisting risk. While methotrexate use is known to possess an increased risk, it had the lowest odds of skin cancer compared to other drugs in the study. Prospective studies are needed to understand the true incidence of skin cancer associated with the use of immunosuppressant drugs. [Table: see text]

Pediatric drug-induced anaphylaxis reports in the FDA Adverse Event Reporting System (FAERS)

Previous research indicated that antibiotics and NSAIDs are key drug categories associated with anaphylaxis in children. However, this study suggests that monoclonal antibodies have emerged as a leading category of drugs reported to the FDA as causing "anaphylaxis" in children. It remains unclear how many of these reports are common-infusion-related reactions rather than true anaphylaxis.