scholarly journals Cardiotoxicity in Biological Agent-Targeted Therapy for Rheumatoid Arthritis: ADR Signal Mining and Analysis of Food and Drug Administration Adverse Event Reporting System Database

2021 ◽  
Vol 9 ◽  
Author(s):  
Xiaoyan Tang ◽  
Xiaolin Xu ◽  
Ji Li ◽  
Bin Zhao
Keyword(s):  
Rheumatoid Arthritis ◽  
Adverse Event ◽  
Reporting System ◽  
Adverse Event Reporting System ◽  
Adverse Event Reporting ◽  
Biological Agents ◽  
Biologic Agents ◽  
Biologic Agent ◽  
Reporting Odds Ratio ◽  
Event Reporting

Purpose: Biologic agent-induced cardiotoxicity is markedly concerning. Rheumatoid arthritis (RA) treated with biologic agents is known to have the potential for cardiotoxicity; however, existing clinical evidence is not adequate to explain real-world patterns of cardiotoxicity. In this study, we quantify the risk of cardiotoxicity in patients with rheumatoid arthritis treated with biological agents.Methods: Cardiotoxicity reports induced by four types of biologic agents, abatacept, adalimumab, tocilizumab, and etanercept were used to mine data from the FDA's adverse event reporting system (FAERS) database from January 1, 2004 through September 30, 2020. Reports of cardiotoxic events were analyzed using a reporting odds ratio (ROR) algorithm, the proportional reporting ratio (PRR), the Bayesian confidence propagation neural network (BCPNN), the multi-item gamma Poisson shrinker (MGPS), and logistic regression methods. We use the preferred term of the Medical Dictionary of Regulatory Activities to identify such events.Results: A total of 3,969 reports of cardiotoxic events were identified involving biologic agents used for RA as the suspect drugs in this study, 317 reports of abatacept, 2,137 reports of adalimumab, 273 reports of tocilizumab, and 1,242 reports of etanercept. Adalimumab was the most reported, followed by etanercept. The proportion of death and disability outcomes reported for each targeted treatment represents approximately 20–25% of the total reported severe adverse events. In addition, relatively low cardiotoxicity reporting rates were found with abatacept.Conclusion: Analysis of FAERS data offers a more precise profile on the characteristics and occurrences of cardiotoxic events. The findings are a clinical reminder to physicians that an increased vigilance concerning the cardiotoxic effects of biological agents needs to be implemented. Also, more comparative studies are required in the future to explain the mechanisms that cause these cardiac phenomena.

scholarly journals Systematic analysis of safety profile for darunavir and its boosted agents using data mining in the FDA Adverse Event Reporting System database

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Xiaojiang Tian ◽  
Yao Yao ◽  
Guanglin He ◽  
Yuntao Jia ◽  
Kejing Wang ◽  
...  
Keyword(s):  
Data Mining ◽  
Adverse Event ◽  
Reporting System ◽  
Proportional Reporting Ratio ◽  
Adverse Event Reporting System ◽  
Adverse Event Reporting ◽  
Reporting Odds Ratio ◽  
Systematic Analysis ◽  
Event Reporting ◽  
Exfoliative Dermatitis

AbstractThis current investigation was aimed to generate signals for adverse events (AEs) of darunavir-containing agents by data mining using the US Food and Drug Administration Adverse Event Reporting System (FAERS). All AE reports for darunavir, darunavir/ritonavir, or darunavir/cobicistat between July 2006 and December 2019 were identified. The reporting Odds Ratio (ROR), proportional reporting ratio (PRR), and Bayesian confidence propagation neural network (BCPNN) were used to detect the risk signals. A suspicious signal was generated only if the results of the three algorithms were all positive. A total of 10,756 reports were identified commonly observed in hepatobiliary, endocrine, cardiovascular, musculoskeletal, gastrointestinal, metabolic, and nutrition system. 40 suspicious signals were generated, and therein 20 signals were not included in the label. Severe high signals (i.e. progressive extraocular muscle paralysis, acute pancreatitis, exfoliative dermatitis, acquired lipodystrophy and mitochondrial toxicity) were identified. In pregnant women, umbilical cord abnormality, fetal growth restriction, low birth weight, stillbirth, premature rupture of membranes, premature birth and spontaneous abortion showed positive signals. Darunavir and its boosted agents induced AEs in various organs/tissues, and were shown to be possibly associated with multiple adverse pregnant conditions. This study highlighted some novel and severe AEs of darunavir which need to be monitored prospectively.

scholarly journals Thrombocytopenia with Tedizolid and Linezolid

2017 ◽  
Vol 62 (1) ◽  
Author(s):  
Erica Yookyung Lee ◽  
Aisling R. Caffrey
Keyword(s):  
Adverse Event ◽  
Confidence Interval ◽  
Drug Administration ◽  
Odds Ratio ◽  
Reporting System ◽  
Adverse Event Reporting System ◽  
Adverse Event Reporting ◽  
Reporting Odds Ratio ◽  
Event Reporting ◽  
Using Data

ABSTRACT Several studies have suggested the risk of thrombocytopenia with tedizolid, a second-in-class oxazolidinone antibiotic (approved June 2014), is less than that observed with linezolid (first-in-class oxazolidinone). Using data from the Food and Drug Administration adverse event reporting system (July 2014 through December 2016), we observed significantly increased risks of thrombocytopenia of similar magnitudes with both antibiotics: linezolid reporting odds ratio [ROR], 37.9 (95% confidence interval [CI], 20.78 to 69.17); tedizolid ROR, 34.0 (95% CI, 4.67 to 247.30).

Adverse event profile differences between rituximab and ocrelizumab: Findings from the FDA Adverse Event Reporting Database

2020 ◽  
pp. 135245852094998
Author(s):  
Natalia Gonzalez Caldito ◽  
Afsaneh Shirani ◽  
Amber Salter ◽  
Olaf Stuve
Keyword(s):  
Adverse Event ◽  
B Cell ◽  
Reporting System ◽  
Adverse Event Reporting System ◽  
Adverse Event Reporting ◽  
Reporting Odds Ratio ◽  
Event Reporting ◽  
Oral Herpes ◽  
Anti Cd20 ◽  
Related Reaction

Background: Rituximab and ocrelizumab are anti-CD20 monoclonal antibodies that have shown a marked reduction in multiple sclerosis (MS) inflammatory activity. However, their real-world safety profile has not been adequately compared. Objective: To investigate the adverse event (AE) profile of rituximab and ocrelizumab reported to the Food and Drug Administration Adverse Event Reporting System (FAERS) database. Methods: The FAERS database was filtered by indication (MS) and drug (rituximab or ocrelizumab). Disproportionality analyses including but not limited to reporting odds ratio (ROR) were conducted to identify drug–AE associations. A signal was detected if the lower limit of the 95% confidence interval of ROR (ROR025) exceeded 1. Results: There were 623 and 7948 reports for rituximab and ocrelizumab, respectively. The most frequent AEs with rituximab and ocrelizumab were infusion-related reaction (4.82%) and urinary tract infection (10.52%), respectively. The strongest drug–AE association for rituximab and ocrelizumab were ear pruritus (ROR025: 47.53) and oral herpes (ROR025: 38.99), respectively. Ocrelizumab was associated with an almost two times higher frequency of infections than rituximab (21.93% vs 11.05%, respectively). Conclusion: This study revealed differences in reporting AEs between rituximab and ocrelizumab. Infections were reported more frequently with ocrelizumab. Although speculative, a potentially different or more extensive B-cell depletion by ocrelizumab might explain these findings. Additional pharmacovigilance studies need to be performed to better characterize differences in the AE profile in B-cell-depleting therapies.

scholarly journals Comparison of Rhabdomyolysis Associated With Sacubitril/valsartan-related Drug-drug Interactions by Individual Statins in an Adverse Event Reporting System

2021 ◽  
Author(s):  
Tomiko Sunaga ◽  
Ryo Yonezawa
Keyword(s):  
Adverse Event ◽  
Drug Interactions ◽  
Reporting System ◽  
Case Reports ◽  
Organic Anion ◽  
Adverse Event Reporting System ◽  
Adverse Event Reporting ◽  
Reporting Odds Ratio ◽  
Event Reporting ◽  
Structured Analysis

Abstract BackgroundSacubitril/valsartan was approved in Japan recently. Sacubitril is an inhibitor of organic anion-transporting polypeptide (OATP) 1B1 and 1B3. In Japan, sacubitril/valsartan product labeling indicates that it should be cautiously co-administered with atorvastatin due to drug-drug interactions (DDIs). However, all statins are the substrates of OATP1B1 and/or 1B3. Therefore, we should be cautious about DDIs between sacubitril/valsartan and all other statins.ObjectiveTo evaluate the association between rhabdomyolysis and concomitant association of sacubitril/valsartan with atorvastatin and all other statins.MethodsCase reports from the U.S. Food and Drug Administration’s Adverse Event Reporting System (FAERS) from 2015 to Q4/2020 were used. All FAERS reports on sacubitril/valsartan were captured through a structured analysis. We compared the proportion of cases reporting the adverse events associated with rhabdomyolysis and the concomitant use of sacubitril/valsartan and atorvastatin to those with sacubitril/valsartan and all other statins.ResultsAmong 10,940 case reports on sacubitril/valsartan, compared with all other drugs, statin users were associated with increased rhabdomyolysis (reporting odds ratio =4.54[2.62-7.87]). However, compared with all other statins, atorvastatin was not associated with increased rhabdomyolysis. ConclusionsWe suggest that the co-administration of sacubitril/valsartan with atorvastatin as well as other statins should be carefully managed as it may induce rhabdomyolysis.

No association between proton pump inhibitor use and dementia risk: data mining of US Food and Drug Administration adverse event reporting system

2021 ◽  
Author(s):  
Bin Wu ◽  
Qiaozhi Hu ◽  
Fangyuan Tian ◽  
Fengbo Wu ◽  
Yuwen Li ◽  
...  
Keyword(s):  
Data Mining ◽  
Adverse Event ◽  
Proton Pump ◽  
Reporting System ◽  
Adverse Event Reporting System ◽  
Adverse Event Reporting ◽  
Reporting Odds Ratio ◽  
Event Reporting ◽  
Long Duration ◽  
Dementia Risk

Abstract Proton pump inhibitors (PPIs) were widely used around the world. Studies suggested conflicting results between PPIs treatment and the risk of dementia. This study examined the association between six PPIs and dementia risk by mining the US FDA Adverse Event Reporting System (FAERS) database from 2004 to 2019. We employed reporting odds ratio (ROR) and proportional reporting ratio (PRR) to detect the signals of dementia relevant to PPIs. We also analyzed characteristics of PPI reports, compared dementia events between short- and long- duration PPIs treatment. Finally, we identified 2104 dementia cases with PPIs treatment. We did not detect significant signals between PPIs and dementia, ROR = 0.99, 95%CI 0.94–1.03, PRR = 0.99, 95%CI 0.95–1.03, even in gastroesophageal reflux disease cases ROR = 0.65, 95%CI 0.58–0.73, PRR = 0.67, 95%CI 0.60–0.74. No significant differences of dementia events were detected between short- and long- duration groups, the OR (95%CI) of the 6 months, 1 year, 3 years and 5 years comparison were 0.85 (0.68–1.06), 0.92 (0.71–1.18), 0.81 (0.57–1.15) and 0.79 (0.52–1.22), respectively. Based on the current FAERS data mining, we discovered no association between PPIs use and the risk of dementia.

scholarly journals Disproportionality Analysis of Safety with Nafcillin and Oxacillin with the FDA Adverse Event Reporting System (FAERS)

2019 ◽  
Vol 64 (3) ◽  
Author(s):  
Tristan T. Timbrook ◽  
Lydia McKay ◽  
Jesse D. Sutton ◽  
Emily S. Spivak
Keyword(s):  
Adverse Event ◽  
Reporting System ◽  
Adverse Event Reporting System ◽  
Adverse Event Reporting ◽  
Lower Proportion ◽  
Reporting Odds Ratio ◽  
Disproportionality Analysis ◽  
Event Reporting ◽  
Content Type ◽  
Failure Reporting

ABSTRACT Antistaphylococcal penicillins such as nafcillin and oxacillin are among the first choices of treatment for severe invasive methicillin-susceptible Staphylococcus aureus (MSSA) infections, although there has been limited safety evaluations between individual agents. Using the FDA Adverse Event Reports System (FAERS), oxacillin was observed to have a lower proportion of reports of acute renal failure (reporting odds ratio [ROR], 5.3 [95% confidence interval {CI}, 3.1 to 9.3] versus 21.3 [95% CI, 15.8 to 28.6], respectively) and hypokalemia (ROR, 0.7 [95% CI, 0.1 to 4.8] versus 11.4 [95% CI, 7.1 to 18.3], respectively) than nafcillin.

scholarly journals Real-world Safety Profile of Darunavir and its Boosted Agents: An Analysis of FDA Adverse Event Reporting System Database

2021 ◽  
Author(s):  
Xiaojiang Tian ◽  
Yao Yao ◽  
Guanglin He ◽  
Yuntao Jia ◽  
Kejing Wang ◽  
...  
Keyword(s):  
Adverse Event ◽  
Adverse Drug Events ◽  
Reporting System ◽  
Proportional Reporting Ratio ◽  
Adverse Event Reporting System ◽  
Adverse Event Reporting ◽  
Reporting Odds Ratio ◽  
Event Reporting ◽  
Exfoliative Dermatitis ◽  
Adverse Pregnancy

Abstract This current investigation was aimed to generate signals for adverse drug events of darunavir-containing agents by data mining using the US Food and Drug Administration Adverse Event Reporting System (FAERS). All adverse event (AE) reports for darunavir, darunavir/ritonavir, or darunavir/cobicistat between July 2006 and December 2019 were identified. The reporting Odds Ratio (ROR), proportional reporting ratio(PRR), Bayesian confidence propagation neural network(BCPNN) were used to detect the risk signals. A suspicious signal was generated only if the results of the three algorithms were all positive. A total of 10756 AE reports were identified commonly observed in cardiovascular, endocrine, musculoskeletal, gastrointestinal, hepatobiliary, metabolic, and nutrition system. 40 suspicious signals were generated, and therein 20 signals were not included in the label. Severe high signals (i.e. progressive extraocular muscle paralysis, acute pancreatitis, exfoliative dermatitis, acquired lipodystrophy and mitochondrial toxicity) were identified. In pregnant women, umbilical cord abnormality, fetal growth restriction, low birth weight, stillbirth, premature rupture of membranes, premature birth and spontaneous abortion showed positive signals. Darunavir and its boosted agents induced AEs in various organs/tissues, and were shown to be associated with multiple adverse pregnancy conditions. This study highlighted some novel and severe AEs of darunavir which need to be monitored prospectively.

scholarly journals Development of a Network-Based Signal Detection Tool: The COVID-19 Adversome in the FDA Adverse Event Reporting System

2021 ◽  
Vol 12 ◽  
Author(s):  
Michele Fusaroli ◽  
Emanuel Raschi ◽  
Milo Gatti ◽  
Fabrizio De Ponti ◽  
Elisabetta Poluzzi
Keyword(s):  
Adverse Event ◽  
Signal Detection ◽  
Reporting System ◽  
Adverse Event Reporting System ◽  
Adverse Event Reporting ◽  
Reporting Odds Ratio ◽  
Event Reporting ◽  
Vein Thrombosis ◽  
Spontaneous Reports ◽  
Effective Signal

Introduction: The analysis of pharmacovigilance databases is crucial for the safety profiling of new and repurposed drugs, especially in the COVID-19 era. Traditional pharmacovigilance analyses–based on disproportionality approaches–cannot usually account for the complexity of spontaneous reports often with multiple concomitant drugs and events. We propose a network-based approach on co-reported events to help assessing disproportionalities and to effectively and timely identify disease-, comorbidity- and drug-related syndromes, especially in a rapidly changing low-resources environment such as that of COVID-19.Materials and Methods: Reports on medications administered for COVID-19 were extracted from the FDA Adverse Event Reporting System quarterly data (January–September 2020) and queried for disproportionalities (Reporting Odds Ratio corrected for multiple comparisons). A network (the Adversome) was estimated considering events as nodes and conditional co-reporting as links. Communities of significantly co-reported events were identified. All data and scripts employed are available in a public repository.Results: Among the 7,082 COVID-19 reports extracted, the seven most frequently suspected drugs (remdesivir, hydroxychloroquine, azithromycin, tocilizumab, lopinavir/ritonavir, sarilumab, and ethanol) have shown disproportionalities with 54 events. Of interest, myasthenia gravis with hydroxychloroquine, and cerebrovascular vein thrombosis with azithromycin. Automatic clustering identified 13 communities, including a methanol-related neurotoxicity associated with alcohol-based hand-sanitizers and a long QT/hepatotoxicity cluster associated with azithromycin, hydroxychloroquine and lopinavir-ritonavir interactions.Conclusion: Findings from the Adversome detect plausible new signals and iatrogenic syndromes. Our network approach complements traditional pharmacovigilance analyses, and may represent a more effective signal detection technique to guide clinical recommendations by regulators and specific follow-up confirmatory studies.

Post-Marketing Safety Concerns with Esketamine: A Disproportionality Analysis of Spontaneous Reports Submitted to the FDA Adverse Event Reporting System

2020 ◽  
Vol 90 (1) ◽  
pp. 41-48
Author(s):  
Chiara Gastaldon ◽  
Emanuel Raschi ◽  
John M. Kane ◽  
Corrado Barbui ◽  
Georgios Schoretsanitis
Keyword(s):  
Adverse Event ◽  
Reporting System ◽  
Adverse Event Reporting System ◽  
Adverse Event Reporting ◽  
Mood Stabilizers ◽  
Reporting Odds Ratio ◽  
Event Reporting ◽  
Completed Suicide ◽  
Spontaneous Reports ◽  
Post Marketing

<b><i>Introduction:</i></b> Esketamine nasal spray received approval for treatment-resistant depression in March 2019. <b><i>Objective:</i></b> Using the FDA Adverse Event Reporting System (FAERS) database (March 2019–March 2020), we analysed esketamine-related adverse events (AEs) to detect and characterize relevant safety signals. <b><i>Methods:</i></b> We used the consolidated case/non-case approach to estimate the reporting odds ratio (ROR) and information component (IC) with relevant confidence intervals (95% CI) for esketamine-related AEs with ≥4 counts. Comparisons between serious and non-serious AEs were performed using non-parametric tests. <b><i>Results:</i></b> The FAERS database contained 962 cases of esketamine-related AEs, with signals detected for several AEs, such as dissociation (ROR = 1,612.64, 95% CI = 1,354.63, 1,919.79; IC = 8.19, 95% CI = 7.96, 8.35), sedation (ROR = 238.46, 95% CI = 202.98, 280.15; IC = 7, 95% CI = 6.75, 7.18), feeling drunk (ROR = 96.17, 95% CI = 61.42, 150.57; IC = 4.84, 95% CI = 4.09, 5.36), suicidal ideation (ROR = 24.03, 95% CI = 18.72, 30.84; IC = 4.31, 95% CI = 3.9, 4.61), and completed suicide (ROR = 5.75, 95% CI = 3.18, 10.41; IC = 2.25, 95% CI = 1.23, 2.94). Signals for suicidal and self-injurious ideation, but not suicide attempt and completed suicide, remained when comparing esketamine to venlafaxine. Females and patients receiving antidepressant polypharmacy, co-medication with mood stabilizers, antipsychotics, benzodiazepines, or somatic medications were more likely to suffer from serious versus non-serious AEs (χ<sup>2</sup> = 125.29, <i>p</i> &#x3c; 0.001, χ<sup>2</sup> = 9.08, <i>p</i> = 0.003, χ<sup>2</sup> = 8.14, <i>p</i> = 0.004, χ<sup>2</sup> = 19.48, <i>p</i> &#x3c; 0.001, χ<sup>2</sup> = 25.62, <i>p</i> &#x3c; 0.001, and χ<sup>2</sup> = 16.79, <i>p</i> &#x3c; 0.001, respectively). <b><i>Conclusions:</i></b> Esketamine may carry a clear potential for serious AEs, which deserves urgent clarification by means of further prospective studies.

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