Characterizing immune checkpoint inhibitor-related cutaneous adverse reactions: A comprehensive analysis of FDA adverse event reporting system (FAERS) database.

Background: The increasing adoption of immune checkpoint inhibitors (ICIs) in clinical settings highlights their efficacy in treating diverse conditions, while also emphasizing the potential for common cutaneous adverse reactions to arise. The aim of this study is to investigate a multitude of impacting factors and determinants among patients presenting with ICI-associated cutaneous adverse reactions. Methods: We conducted a comprehensive analysis of ICI-associated cutaneous adverse reactions using data from the FAERS. Our study spans from January 1, 2015, to March 31, 2023, focusing on ICIs, including anti-PD-1, anti-PD-L1, and anti-CTLA-4 agents. Findings: Among the 334,293 reported irAR, 17,431 were identified as cutaneous adverse reactions (ARs). Predominant cutaneous ARs included rash (21.01 %), pruritus (11.22 %), and pemphigoid (3.90 %). Stevens-Johnson syndrome emerged as the most reported severe cutaneous adverse reaction (SCAR) (2.08 %). Anti-CTLA-4 agents exhibited higher cutaneous toxicity compared to anti-PD-1 and anti-PD-L1 agents. Anti-PD-1 agents demonstrated an elevated mortality rate. The combined use of ICIs with chemotherapy amplified the risk of SCAR and mortality. Targeted therapy was a risk factor for cutaneous ARs but was associated with reduced mortality. The median onset day for cutaneous toxicity was 21 days, while for SCAR, it was 23 days. Weight and age were identified as predictors of SCAR, cutaneous toxicity, and mortality. Skin cancer increased skin toxicity, while lung cancer heightened SCAR formation. The number of administered ICIs positively correlated with SCAR, skin toxicity, and mortality. Interpretation: This study highlights the significance of early identification and effective management of cutaneous toxicities, along with personalized follow-up care, as essential strategies for minimizing risks and preventing treatment disruptions.

Assessment of adverse events related to anti-interleukin-6 receptor monoclonal antibodies using the FDA adverse event reporting system:a real-world pharmacovigilance study.

BACKGROUND: Interleukin-6 (IL-6) monoclonal antibodies are commonly acknowledged for their efficacy in managing coronavirus disease 2019 (COVID-19); however, there remains a paucity of comprehensive studies on their potential adverse effects. RESEARCH DESIGN AND METHODS: This is a retrospective pharmacovigilance investigation. We employed FAERS using OpenVigil FDA to detect adverse reactions linked to the interleukin-6 antagonist tocilizumab and sarilumab. RESULTS: Completely 17,037,364 reports were collected from the FAERS database, with 67,976 reports identified as 'primary suspected (PS)' adverse events (AEs) for tocilizumab, and 12,560 reports for sarilumab. AEs induced by both drugs involved 27 organ systems. 109 significant disproportionality preferred terms (PTs) of tocilizumab and 158 significant disproportionality PTs meeting the criteria of sarilumab across all four algorithms were retained simultaneously. A higher incidence of adverse reactions occurred in females aged 45-64 years, with a higher rate of subsequent hospitalization. Both drugs exhibited adverse reactions consistent with previously reported side effects, such as leukopenia, elevated liver enzymes, and hypercholesterolemia. Additionally, there was a strong correlation with gastrointestinal issues. Unexpected significant adverse events, including diabetes, fluctuations in blood pressure, drug ineffectiveness, malignancies, and disorders of the nervous system, were also observed. Gender and age differences existed in AEs signals related to IL-6RAs. CONCLUSION: Our study identified significant new AE signals for interleukin-6 receptor antagonists, potentially supporting clinical monitoring and risk identification for this class of drugs.

PARP inhibitor-related acute renal failure: a real-world study based on the FDA adverse event reporting system database.

BACKGROUND: Current clinical trial data on PARP inhibitors (PARPis)-related acute renal failure (ARF) are not entirely representative of real-world situations. Therefore, in this study, the US Food and Drug Administration Adverse Event Reporting System (FAERS) was used to evaluate PARPis-related ARF. RESEARCH DESIGN AND METHODS: Data were obtained from 1 January 2015, to 30 September 2023. ARF event reports were analyzed based on four algorithms. The time-to-onset (TTO) and clinical outcomes of PARPis-associated ARF were assessed. RESULTS: The total included cases were 2726. Significant signals were observed for olaparib, niraparib, and rucaparib (reporting odds ratio (ROR): 1.62, 95% confidence interval (CI): 1.49-1.78, 1.25, 95% CI: 1.19-1.32 and 1.59, 95% CI: 1.47-1.72 respectively). The median TTO of ARF onset was 57, 36, and 85 days for olaparib, niraparib, and rucaparib, respectively. The proportion of deaths with olaparib (9.88%) was significantly higher than for niraparib (2.52%) and rucaparib (2.94%) (p < 0.005). The proportion of life-threatening adverse events associated with niraparib (4.89%) was significantly higher than for rucaparib (0.98%) (p < 0.005). CONCLUSIONS: ARF and PARPi were related, with the exception of talazoparib. More emphasis should be given to PARPis-related ARF due to the high proportion of serious AEs and delayed adverse reactions.

Clinical adverse events to dexmedetomidine: a real-world drug safety study based on the FAERS database.

Objective: Adverse events associated with dexmedetomidine were analyzed using data from the FDA's FAERS database, spanning from 2004 to the third quarter of 2023. This analysis serves as a foundation for monitoring dexmedetomidine's safety in clinical applications. Methods: Data on adverse events associated with dexmedetomidine were standardized and analyzed to identify clinical adverse events closely linked to its use. This analysis employed various signal quantification analysis algorithms, including Reporting Odds Ratio (ROR), Proportional Reporting Ratio (PRR), Bayesian Confidence Propagation Neural Network (BCPNN), and Multi-Item Gamma Poisson Shrinker (MGPS). Results: In the FAERS database, dexmedetomidine was identified as the primary suspect in 1,910 adverse events. Our analysis encompassed 26 organ system levels, from which we selected 346 relevant Preferred Terms (PTs) for further examination. Notably, adverse drug reactions such as diabetes insipidus, abnormal transcranial electrical motor evoked potential monitoring, acute motor axonal neuropathy, and trigeminal cardiac reflex were identified. These reactions are not explicitly mentioned in the drug's specification, indicating the emergence of new signals for adverse drug reactions. Conclusion: Data mining in the FAERS database has elucidated the characteristics of dexmedetomidine-related adverse drug reactions. This analysis enhances our understanding of dexmedetomidine's drug safety, aids in the clinical management of pharmacovigilance studies, and offers valuable insights for refining drug-use protocols.

Neuronal toxicity of monoclonal antibodies (mAbs): an analysis of post-marketing reports from FDA Adverse Event Reporting System (FAERS) safety database.

BACKGROUND: Monoclonal antibodies (mAbs) are pivotal in treating various diseases, including cancers and autoimmune disorders. Despite their therapeutic benefits, mAb therapy has been associated with neurological toxicity. OBJECTIVES: This study aimed to assess the occurrence of neuronal toxicity associated with mAbs, utilizing data from the FDA Adverse Event Reporting System (FAERS) safety database. The study also sought to delineate the medical characteristics of the reported cases. METHODS: A comprehensive analysis of neurological adverse events reported in the FAERS database was conducted, employing computational methodologies such as proportional relative risk (PRR), information component (IC025), and chi-square (χ2). Individual case safety reports (ICSRs) pertaining to neurological disorders linked to mAbs from the date of first global marketing authorization until June 30, 2023, were meticulously examined. RESULTS: The FAERS safety database contains 79,022 ICSRs linking mAbs to nervous system disorders. Rituximab, bevacizumab, denosumab, nivolumab, and trastuzumab were frequently cited. Reported adverse events include headache, peripheral neuropathy, dizziness, and cerebrovascular accident. Most ICSRs (85.81%) were serious, mainly affecting females (57.04%) with a 14.09% fatality rate. Panitumumab, atezolizumab, bevacizumab, and trastuzumab showed strong drug-event associations. Signal disproportionate reporting (SDR) analysis flagged myasthenia gravis, peripheral neuropathy, and neurotoxicity across multiple mAbs, suggesting potential signals. CONCLUSIONS: Interdisciplinary collaboration between oncologists and neurologists is crucial for safe mAb use. Our study enhances understanding of mAb neurological safety. Disproportionality signal analysis provides valuable evidence for risk mitigation.

A retrospective pharmacovigilance study of post-marketing safety concerns with cefuroxime.

Background: Cefuroxime has played a crucial role in the prevention and treatment of bacterial infections. However, the differences in adverse events across formulations and routes remain unclear. Objectives: This study aimed to investigate the post-marketing safety of cefuroxime, particularly concerning formulations and routes. Design: A retrospective pharmacovigilance study of cefuroxime was conducted using the data from Food and Drug Administration Adverse Event Reporting System database. Methods: The clinical characteristics and concomitant drugs reported with cefuroxime were investigated. Adverse event signals of cefuroxime were identified based on four disproportionality algorithms. The signal differences of cefuroxime across formulations and routes were further examined. Results: A total of 1810 adverse event reports associated with cefuroxime were identified, and 181 cefuroxime-associated signals were detected. Compared with tablets, injections were more likely to cause preferred terms 'blood pressure decreased' and 'anaphylactic shock'. In addition, system organ class 'eye disorders' significantly increased when cefuroxime was administered intraocularly, underscoring the importance of exercising caution regarding ocular toxicity. Conclusion: The adverse events associated with cefuroxime were significantly different across formulations and routes, which deserve special attention in clinical use.

Background: Cefuroxime is a commonly used antibiotic. This study investigated the safety of cefuroxime using Food and Drug Administration Adverse Event Reporting System database. Research design and methods: We analyzed the clinical characteristics and concomitant drugs reported with cefuroxime. Then, we detected the signals of cefuroxime. We further examined the signal differences of cefuroxime across formulations and routes. Results: We retrieved 1810 reports and identified 181 signals associated with cefuroxime. In comparison to tablets, injections had a higher likelihood of causing decreased blood pressure and anaphylactic shock. Furthermore, the administration of cefuroxime intraocularly increased the possibility of experiencing eye disorders. Conclusion: The signals associated with cefuroxime were significantly different across formulations and routes, which deserve special attention in clinical use.

Post-marketing safety concerns with cefuroxime.

Cardiovascular events of Bruton's tyrosine kinase inhibitors: A real-world study based on the United States Food and Drug Administration Adverse Event Reporting System database.

AIMS: Bruton's tyrosine kinase inhibitors (BTKIs), including first-generation ibrutinib, second-generation acalabrutinib and zanubrutinib, may be involved in the mechanisms of action related to adverse events (AEs) of the cardiovascular system. We aimed to characterize the cardiovascular AEs of BTKIs reported in the US Food and Drug Administration (FDA) Adverse Event Reporting System, and to compare the cardiovascular risks of BTKIs. METHODS: Across all indications of three FDA-approved BTKIs, primary suspect drugs were extracted over two periods: from January 2013 to December 2022 (after the approval of the first BTKI), and from January 2020 to December 2022 (all three BTKIs on the market). Disproportionality was measured by reporting odds ratios (RORs) and information components. Additional analyses were performed without incorporating patients with underlying cardiovascular disease (CVD). RESULTS: A total of 10 353 cases included the uses of ibrutinib, acalabrutinib and zanubrutinib. Ibrutinib was significantly associated with 47 cardiovascular AEs. Acalabrutinib was associated with new signals, including cardiac failure (ROR = 1.82 [1.13-2.93]), pulmonary oedema (ROR = 2.15 [1.19-3.88]), ventricular extrasystoles (ROR = 5.18 [2.15-12.44]), heart rate irregular (ROR = 3.05 [1.53-6.11]), angina pectoris (ROR = 3.18 [1.71-5.91]) and cardiotoxicity (ROR = 25.22 [17.14-37.10]). In addition, cardiovascular events had an earlier onset in acalabrutinib users. Zanubrutinib was only associated with atrial fibrillation. Acalabrutinib and zanubrutinib had lower ROR values than ibrutinib. The AE signals were generally consistent between the population receiving and not receiving CVD medications. CONCLUSIONS: Potential cardiovascular risks identified in this study were not clearly noted on the label of marketed acalabrutinib. Caution should be paid to the cardiovascular risks of BTKIs having been or being developed.

The association between ketamine and esketamine and suicidality: reports to the Food And Drug Administration Adverse Event Reporting System (FAERS).

INTRODUCTION: Replicated evidence indicates that ketamine and esketamine reduce measures of suicidality in persons with treatment-resistant depression (TRD). It remains uncertain whether individuals experience worsening of preexisting suicidality with either agent. RESEARCH DESIGN AND METHODS: The Food and Drug Administration Adverse Event Reporting System (FAERS) database was searched from 1970 and 2019 to 30 September 2023 for reports of suicidal ideation, depression suicidal, suicidal behavior, suicidal attempt, and completed suicide in association with ketamine and esketamine exposure, respectively. We present reporting odds ratios (ROR) significance was determined when the lower limit of the 95% confidence interval (CI) exceeded 1.0. Lithium was used as the control agent. RESULTS: Observed a higher ROR for suicidal ideation (ROR 7.58, 95% CI 6.34-9.07) and depression suicidal (ROR 14.19, 95% CI 1.80-112.07) with esketamine. Significantly lower RORs were observed for suicide attempt with ketamine (ROR 0.15, 95% CI 0.11-0.21) and esketamine (ROR 0.57, 95% CI 0.48-0.67). CONCLUSIONS: Mixed RORs across aspects of suicidality were observed with ketamine and esketamine. Limitations of the FAERS database prevent any determination of causal effects new onset suicidality to either agent. The lower RORs for suicide attempt with ketamine and esketamine is noted but cannot be interpreted as a direct therapeutic effect.

Analysis of adverse drug reactions of Denosumab (Prolia) in osteoporosis based on FDA adverse event reporting system (FAERS).

Objective: To comprehensively analyze the ADRs associated with Denosumab (Prolia) in the treatment of osteoporosis using data from the FAERS database, and gain a better understanding of the potential risks and side effects of Denosumab (Prolia) therapy. Methods: Data of Denosumab (Prolia) were collected from the FAERS database covering the period from first quarter of 2010 to the third quarter of 2023. Disproportionality analysis was performed by calculating the reporting odds ratios (ROR), proportional reporting ratio (PRR), and Bayesian analysis confidence propagation neural network (BCPNN) to detect positive signals. Results: Totally, 17,985,365 reports were collected from the FAERS database, 1,97,807 reports of Denosumab (Prolia) were identified as the "primary suspected (PS)" ADRs. Denosumab (Prolia) induced ADRs occurred in 27 organ systems. 38 significant disproportionality PTs satisfying with the three algorithms were retained at the same time. Unexpected significant ADRs such as bone density abnormal and immobile also occur. The majority of the ADRs occurred within the first 30 days after Denosumab (Prolia) initiation. Conclusion: Based on the American FAERS database, the high frequency ADRs of Denosumab (Prolia) were hypocalcaemia, bone density abnormal, eczema, rebound effect, spinal deformity, etc. Clinical use of this drug should focus on this part of ADRs. Attention should also be paid to newly discovered ADRs, such as immobile, menopausal symptoms, etc., to avoid more serious consequences. Cohort studies, more detailed and comprehensive case information, and long-term clinical investigations are needed to confirm these results and to further understand the safety profile of Denosumab (Prolia).

Prolonged Diabetic Ketoacidosis Associated With Sodium-Glucose Cotransporter-2 Inhibitors: A Review of Postmarketing Cases.

OBJECTIVE: To describe reported cases of prolonged or relapsed ketoacidosis (KA) in adults with type 2 diabetes receiving treatment with sodium-glucose cotransporter-2 (SGLT2) inhibitors. METHODS: We performed a search of the U.S. Food and Drug Administration (FDA) Adverse Event Reporting System and medical literature, to identify our case series and to characterize cases of prolonged KA, relapsed KA, or persistent ketonemia, persistent ketonuria and/or persistent glucosuria in adults receiving SGLT2 inhibitors. RESULTS: The FDA identified 29 unique cases of prolonged or relapsed KA, as well as related terms persistent ketonemia, persistent ketonuria, and persistent glucosuria, in patients receiving SGLT2 inhibitors through July 26, 2022. The patients ranged in age from 26 to 85 years. Treatment duration of KA ranged from 3 to 20 days. There were 7 cases of relapsed KA when insulin was reduced or transitioned to subcutaneous route. Arterial pH value was 7.0 or below in 4 patients, and the median pH was 7.1. Associated factors for prolonged or relapsed KA included surgery, decreased caloric intake, and ketogenic/carbohydrate restricted diet. A total of 62% of the patients were taking 3 or more glycemic control medications including the SGLT2 inhibitor. All patients with sufficient follow-up information recovered. CONCLUSION: Although KA is a well-known risk associated with SGLT2 inhibitors, this case series demonstrated the potential for prolonged or recurrent KA events with serious outcomes. These cases informed updates to FDA's prescribing information to inform prescribers of this risk.

Safety of cardiovascular disease drugs approved between 2014 and 2021 in the US: a pharmacovigilance analysis.

BACKGROUND: Recently FDA-approved drugs for cardiovascular disease (CVD) require robust post-marketing surveillance. The objective of this study was to assess their safety using a large pharmacovigilance database. RESEARCH DESIGN AND METHODS: We analyzed adverse event (AE) reports for 17 drugs approved from 2014 to 2021, utilizing the FDA Adverse Event Reporting System (FAERS). Descriptive and disproportionality analyses were conducted by estimating the reporting odds ratio (ROR) and its 95% confidence interval. RESULTS: Among the 43,664,773 AE reports 97,702 (0.22%) were related to newly approved CVD drugs. No AEs were reported for finerenone and evinacumab. The results from the disproportionality analyses revealed potential risks of acute kidney injury (ROR = 8.24, 95% CI: 6.05-11.22), cardiac failure (ROR = 4.80, 95% CI: 3.82-6.05), and hypotension (ROR = 3.98, 95% CI: 3.44-4.61) among sacubitril/valsartan users. Additionally, ivabradine was found to be associated with tachycardia (ROR = 11.94, 95% CI: 8.35-17.08), abnormal feeling (ROR = 4.40, 95% CI: 2.70-7.18), and dizziness (ROR = 2.56, 95% CI: 1.68-3.90). CONCLUSIONS: This study identified specific safety concerns related to recently approved CVD drugs. Further research is required to understand the underlying mechanisms and clinical implications of these findings.

The association between ketamine and esketamine with alcohol and substance misuse: Reports to the Food and Drug Administration adverse event reporting system (FAERS).

INTRODUCTION: Ketamine and esketamine have been proven to be effective in treating adults with treatment resistant depression (TRD). Preliminary evidence indicates that, when combined with behavioral and psychological interventions, both agents may offer benefits for individuals with substance use disorder (SUD) and alcohol use disorder (AUD). Notwithstanding, concerns have been raised as to whether either or both agents are associated with abuse and/or gateway activity. METHODS: Herein, we evaluate disproportionate reporting expressed as reporting odds ratios (ROR) for esketamine and ketamine. The outcomes of interest include alcohol problem, alcoholism, alcohol abuse, substance dependence, SUD, substance abuse, drug dependence, drug use disorder and drug abuse as codified by the Medical Dictionary for Regulatory Activities (MedDRA) within the FAERS. The IC025 values were significant for ketamine in cases of alcohol abuse (0.28), substance dependence (1.88), substance use disorder (0.996), substance abuse (0.61), drug dependence (0.56), drug use disorder (1.17) and drug abuse (1.22). Additionally, oxycontin showed significant IC025 values for substance dependence (0.067), substance use disorder (0.094), substance abuse (0.035), and drug dependence (0.27). RESULTS: We observed significant increases in the reporting odds ratios (RORs) for ketamine with respect to various outcomes: alcohol abuse (ROR 2.84, 95 % CI 1.53-5.28; p = 0.0010), substance dependence (ROR 18.72, 95 % CI 8.49-41.30; p ≤ 0.0001), SUD (ROR 11.40, 95 % CI 4.24-30.65; p ≤ 0.0001), substance abuse (ROR 2.29, 95 % CI 1.73-3.04; p ≤ 0.0001), drug dependence (ROR 1.99, 95 % CI 1.64-2.42; p ≤ 0.0001), drug use disorder (ROR 4.50, 2.94-6.88; p ≤ 0.0001) and drug abuse (ROR 3.72, 3.36-4.12; p ≤ 0.0001). For esketamine, we observed that the ROR was significantly reduced for substance abuse (ROR 0.37, 95 % CI 0.22-0.63; p = 0.0003), drug dependence (ROR 0.13, 95 % CI 0.076-0.23; p ≤ 0.0001) and drug abuse (ROR 0.048, 95 % CI 0.030-0.078; p ≤ 0.0001). To our knowledge, this is the first report of spontaneous adverse events related to these outcomes of interest in the FAERS. CONCLUSION: Mixed RORs were observed across aspects of SUD and AUD for both ketamine and esketamine. Due to limitations in the FAERS, establishing causal links between new onset alcohol and substance misuse with either agent remains inconclusive. Possible beneficial effects on measures of SUD and AUD were observed. It is currently unclear, but possible, whether both agents have differential ameliorative effects across dimensions of SUD and AUD, which is a focus of ongoing research.

Relationship between Anaplastic Lymphoma Kinase Inhibitors and Epileptic Seizure Disorder: A Post-Marketing Surveillance Study.

INTRODUCTION: Anaplastic lymphoma kinase (ALK) has been to be involved in the uptake and regulation of dopamine 2 receptor (D2R), a G protein-coupled receptor expressed in various brain regions. Therefore, it is crucial to understand the relationship between ALK inhibitors and seizures is an important issue. This study investigated the relationship between ALK inhibitors and seizures. METHODS: This study investigated the relationship between ALK inhibitors and seizures through a disproportionality analysis using the US Food and Drug Administration (FDA) Adverse Event Reporting System (FAERS). The target drugs were the ALK inhibitors crizotinib, ceritinib, alectinib, brigatinib, and lorlatinib. The seizures covered were defined high-level group term (HLGT): "Seizures (incl. subtype)" including high-level term (HLT): "seizures and seizure disorders NEC." This study used the information component (IC), a signal score, as a Bayesian statistical method for disproportionality analysis. The signal detection criteria used in this study were the same as those reported previously: a lower limit of 95% credible interval (CrI) for IC >0. RESULTS: The signal scores of '"seizures and seizure disorders not elsewhere classified (NEC)" "for each ALK inhibitor were crizotinib (IC: -0.00052, 95% CrI: -0.38-0.27), ceritinib (IC: 1.18, 95% CrI: 0.68-1.54), alectinib (IC: 0.68, 95% CrI: 0.19-1.02), brigatinib (IC: 1.04, 95% CrI: 0.32-1.54), and lorlatinib (IC: 0.82, 95% CrI: 0.11-1.32). On the other hand, "generalized tonic-clonic seizures," "partial simple seizures NEC," "absence seizures," and "partial complex seizures" had no or few reported cases, and no signal was detected. CONCLUSION: To our knowledge, this is the first report to evaluate the relationship between ALK inhibitors and seizures using post-marketing surveillance data. These results suggest that ceritinib, alectinib, brigatinib, and lorlatinib, which are highly brain-migrating drugs, are associated with seizures.

Thyroid Hyperplasia and Neoplasm Adverse Events Associated With Glucagon-Like Peptide-1 Receptor Agonists in the Food and Drug Administration Adverse Event Reporting System: Retrospective Analysis.

Background: Glucagon-like peptide-1 (GLP-1) receptor agonists (RAs) are one of the most commonly used drugs for type 2 diabetes mellitus. Clinical guidelines recommend GLP-1 RAs as an adjunct to diabetes therapy in patients with chronic kidney disease, presence or risk of atherosclerotic cardiovascular disease, and obesity. The weight loss observed in clinical trials has been explored further in healthy individuals, putting GLP-1 RAs on track to be the next weight loss treatment. Objective: Although the adverse event profile is relatively safe, most GLP-1 RAs come with a labeled boxed warning for the risk of thyroid cancers, based on animal models and some postmarketing case reports in humans. Considering the increasing popularity of this drug class and its expansion into a new popular indication, a further review of the most recent postmarketing safety data was warranted to quantify thyroid hyperplasia and neoplasm instances. Methods: GLP-1 RA patient reports from the US Food and Drug Administration (FDA) Adverse Event Reporting System database were analyzed using reporting odds ratios and 95% CIs. Results: In this study, we analyzed over 18 million reports from the US FDA Adverse Event Reporting System and provided evidence of significantly increased propensity for thyroid hyperplasias and neoplasms in patients taking GLP-1 RA monotherapy when compared to patients taking sodium-glucose cotransporter-2 (SGLT-2) inhibitor monotherapy. Conclusions: GLP-1 RAs, regardless of indication, are associated with an over 10-fold increase in thyroid neoplasm and hyperplasia adverse event reporting when compared to SGLT-2 inhibitors.

Exploring the association between weight loss-inducing medications and multiple sclerosis: insights from the FDA adverse event reporting system database.

Background: Several studies have demonstrated that early childhood and adolescent obesity are risk factors for multiple sclerosis (MS) susceptibility. Obesity is thought to share inflammatory components with MS through overproduction of pro-inflammatory adipokines (e.g., leptin) and reduction of anti-inflammatory adipokines (e.g, adiponectin). Recently, drug repurposing (i.e. identifying new indications for existing drugs) has garnered significant attention. The US Food and Drug Administration Adverse Event Reporting System (FAERS) database serves not only as a resource for mining adverse drug reactions and safety signals but also for identifying inverse associations and potential medication repurposing opportunities. Objective: We aimed to explore the association between weight-loss-inducing drugs and MS using real-world reports from the FAERS database. Design: Secondary analysis of existing data from the FAERS database. Methods: We conducted a disproportionality analysis using the FAERS database between the fourth quarter of 2003 and the second quarter of 2023 to explore associations between MS and weight loss-inducing drugs. Disproportionality was quantified using the reporting odds ratio (ROR). An inverse association was defined when the upper limit of the 95% confidence interval for ROR was <1. Results: We found an inverse association between MS and anti-diabetic weight loss-inducing drugs including semaglutide (ROR: 0.238; 95% CI: 0.132-0.429), dulaglutide (ROR: 0.165; 95% CI: 0.109-0.248), liraglutide (ROR: 0.161; 95% CI: 0.091-0.284), empagliflozin (ROR: 0.234; 95% CI: 0.146-0.377), and metformin (ROR: 0.387; 95% CI: 0.340-0.440). No inverse associations were found for other weight loss-inducing drugs such as phentermine, bupropion, topiramate, zonisamide, and amphetamine. An exception was naltrexone (ROR: 0.556; 95% CI: 0.384-0.806). Conclusion: Our findings suggest a potential consideration for repurposing anti-diabetic weight loss-inducing drugs including semaglutide, dulaglutide, and liraglutide (glucagon-like peptide-1 receptor agonists), empagliflozin (sodium-glucose cotransporter-2 inhibitor), and metformin (biguanide), for MS. This warrants validation through rigorous methodologies and prospective studies.

A disproportionality analysis of FDA adverse event reporting system (FAERS) events for ticagrelor.

Background: Ticagrelor is a commonly used antiplatelet agent, but due to the stringent criteria for trial population inclusion and the limited sample size, its safety profile has not been fully elucidated. Method: We utilized OpenVigil 2.1 to query the FDA Adverse Event Reporting System database and retrieved reports by the generic name "ticagrelor" published between 1 October 2010 and 31 March 2023. Adverse drug events (ADEs) were classified and described according to the preferred terms and system organ classes in the Medical Dictionary of Regulatory Activity. Proportional reporting ratio (PRR), reporting odds ratio (ROR) and Bayesian Confidence Propagation Neural Network (BCPNN) were used to detect signals. Results: The number of ADE reports with ticagrelor as the primary suspect drug was 12,909. The top three ADEs were dyspnea [1824 reports, ROR 7.34, PRR 6.45, information component (IC) 2.68], chest pain (458 reports, ROR 5.43, PRR 5.27, IC 2.39), and vascular stent thrombosis (406 reports, ROR 409.53, PRR 396.68, IC 8.02). The highest ROR, 630.24, was found for "vascular stent occlusion". Cardiac arrest (137 reports, ROR 3.41, PRR 3.39, IC 1.75), atrial fibrillation (99 reports, ROR 2.05, PRR 2.04, IC 1.03), asphyxia (101 reports, ROR 23.60, PRR 23.43, IC 4.51), and rhabdomyolysis (57 reports, ROR 2.75, PRR 2.75, IC 1.45) were suspected new adverse events of ticagrelor. Conclusion: The FAERS database produced potential signals associated with ticagrelor that have not been recorded in the package inserts, such as cardiac arrest, atrial fibrillation, asphyxia, and rhabdomyolysis. Further clinical surveillance is needed to quantify and validate potential hazards associated with ticagrelor-related adverse events.

Adverse events of nivolumab plus ipilimumab versus nivolumab plus cabozantinib: a real-world pharmacovigilance study.

BACKGROUND: No head-to-head clinical trials have compared the differences in adverse events (AEs) between nivolumab plus ipilimumab (NIVO-IPI) and nivolumab plus cabozantinib (NIVO-CABO) in the treatment of metastatic renal cell carcinoma (mRCC). AIM: We analysed the two largest real-world databases, the U.S. Food and Drug Administration Adverse Event Reporting System (FAERS) and the World Health Organization's VigiBase, to elucidate the differences in AEs between NIVO-IPI and NIVO-CABO. METHOD: In total, 40,376 and 38,022 records were extracted from FAERS and VigiBase, and 193 AEs were analysed. The reporting odds ratios (ROR) with 95% confidence interval were calculated using a disproportionality analysis (NIVO-CABO/NIVO-IPI). RESULTS: The reported numbers of immune-related AEs, including myocarditis, colitis, and hepatitis, were significantly higher with NIVO-IPI (ROR = 0.18 for FAERS and 0.13 for VigiBase). Contrarily, the reported numbers of other AEs, including gastrointestinal disorders (ROR = 2.68 and 2.92) and skin and subcutaneous tissue disorders (ROR = 2.94 and 3.55), considered to be potentiated by the combination of NIVO and CABO, were higher with NIVO-CABO. CONCLUSION: Our findings contribute to the selection and clinical management of NIVO-IPI and NIVO-CABO, which minimizes the risk of AEs for individual patients with mRCC by considering distinctive differences in the AE profiles.

Mining and analysis of security alert signals of valbenazine based on the Food and Drug Administration Adverse Event Reporting System database.

BACKGROUND: Valbenazine is used for tardive movement disorders in adults. Current studies on its safety are mostly from clinical trials and small case reports, limiting information on rare adverse reactions. This study investigated valbenazine-related adverse event (AE) risk signals using the U.S. Food and Drug Administration Adverse Event Reporting System (FAERS) database. METHODS: Valbenazine AEs data were collected from the FAERS database from 2017 Q2 to 2023 Q1, employing methods like reporting odds ratio (ROR), proportional reporting ratio (PRR), Bayesian confidence propagation neural network, and empirical Bayesian geometric mean. RESULTS: After data cleaning and drug screening, there were 20,837 AEs primarily suspecting valbenazine, involving 26 system organ classes and 125 AEs related to valbenazine at the preferred terms level. AEs related to valbenazine were mainly concentrated in nervous system disorders, general disorders and administration site conditions, and psychiatric disorders. Eye disorders and gastrointestinal disorders are new AEs not labeled in the valbenazine instructions. In addition, some new potential AE signals were found, such as Tardive dyskinesia and eyelid function disorder. CONCLUSION: The common AEs of valbenazine in the real world are consistent with the instructions, but there are some newly discovered suspicious AEs.