Expert Opinion on Drug Safety最新文献

Background: Ruxolitinib cream, a topical Janus kinase (JAK) inhibitor, is a widely used treatment for various dermatological diseases. This study employs the FDA Adverse Event Reporting System (FAERS) database to examine adverse events (AEs) associated with ruxolitinib cream.

Methods: This study employed disproportionate analysis methods, including reported odds ratio and proportional reporting ratio, to collate AEs reported from the fourth quarter of 2021 to the first quarter of 2024.

Results: After data processing, 803 reports involving ruxolitinib cream were analyzed. Statistically significant signals were identified for 4 system organ classes (SOCs) and 29 preferred terms (PTs). The most notable signal observed in the SOCs was associated with skin and subcutaneous tissue disorders. For PTs, the AEs observed included clinical symptoms such as pruritus, skin irritation, and burning sensations, as well as signs such as rash, scratching, erythema, and dry skin. Additionally, other observed AEs included diseases such as acne, drug hypersensitivity, and herpes zoster.

Conclusions: This study offers insights into the safety of ruxolitinib cream, improving understanding of its AEs and guiding safer clinical practices. However, the FAERS database lacks data on AE severity and the ability to establish causality, requiring further research to clarify mechanisms behind certain AEs.

Background: Several studies have indicated a potential link between calcineurin inhibitors (CNIs) and skin cancers. However, comprehensive evidence of CNI-induced skin cancers remains lacking.

Research design and methods: We conducted an observational retrospective pharmacovigilance study utilizing the FAERS database to identify potential risk signals associated with skin cancers with CNIs treatment, encompassing data from its inception to the third quarter of 2023. The assessment was carried out using the Information Component (IC) and Reporting Odds Ratio (ROR).

Results: We identified 1339 cases of skin cancers linked to CNIs use. The frequency of skin cancers associated with both CsA and Tac was significantly higher compared to all other drugs in the database, especially for nonmelanoma skin cancer (NMSC). There was no significant difference in the risk of CsA-related melanoma skin cancer (MSC) and NMSC compared to Tac. Additionally, the development of MSC appeared to have a higher risk of fatal outcomes in individuals of Caucasian descent and patients aged 40-79 years.

Conclusions: Our study has provided new real-world evidence regarding the safety of CNIs concerning skin cancers. It is recommended that clinicians remain vigilant about CNI-associated skin cancers and implement early surveillance to prevent adverse outcomes.

Background: Recent clinical case reports have generated controversy concerning the adverse events (AEs) of amputation linked to sodium-glucose co-transporter 2 inhibitors (SGLT2i). We assessed the risk of osteomyelitis AE reporting linked to SGLT2i or SGLT2i-metformin co-medication.

Research design and methods: Investigated the FDA Adverse Event Reporting System for osteomyelitis-related AEs associated with SGLT2i or SGLT2i-metformin co-medication from 2013q2 to 2023q1. Comprehensive disproportionality analysis and Bayesian confidence propagation methods were used to detect safe signals. The additive interaction model, multiplicative interaction model, and Ω shrinkage measure were employed to explore the latent interactions between SGLT2i and metformin. A Venn diagram was utilized to estimate the coincidence of related osteomyelitis and amputation.

Results: Among 2,569 SGLT2i-associated osteomyelitis reports, we identified 2,509 related to canagliflozin (ROR 104.47; PRR 99.70, χ2 = 214840.90; EBGM05 = 84.38; IC025 = 4.78) and 103 related to the SGLT2i-metformin compound. Drug-drug interaction detection revealed a negative correlation RERI = -21.73, e^β3 = 0.699, Ω025=-1.370). The coincidence of osteomyelitis and amputation linked to SGLT2i (2,672 vs. 3,548) was 2,150(80%) by Venn diagram.

Conclusions: This study showed an increased risk of SGLT2i-associated osteomyelitis, focusing on canagliflozin, and presented a potential association between amputation and osteomyelitis, providing a reference for the clinical practice of diabetes with SGLT2i medication.

Background: Fabry disease (FD), an X-linked lysosomal disorder, is marked by a lack of alpha-galactosidase A (α-Gal A). Agalsidase beta, a recombinant form of α-Gal A, is fundamental to enzyme replacement therapy for FD but requires close monitoring for adverse events (AEs).

Research design and methods: This study retrospectively analyzed the Food and Drug Administration Adverse Event Reporting System (FAERS) database for agalsidase beta-related AEs. Disproportionality analysis was used for data analysis.

Results: A total of 7,611 AE reports for agalsidase beta were analyzed. The most common AEs included pyrexia, pain, chills, malaise, and nausea. Several system organ classes including Cardiac Disorders, General Disorders and Administration Site Conditions, and Vascular Disorders, showed positive signals. Subgroup analysis by gender revealed differences in AE reporting, with males exhibiting a higher reporting odds ratio for certain preferred terms such as Renal Transplant and Drug Specific Antibody Present.

Conclusion: The FAERS database analysis of agalsidase beta AEs identified a significant number of cardiovascular, renal, and cerebrovascular system-related reports. While agalsidase beta is generally well-tolerated, the study underscores the necessity for gender-specific treatment approaches due to the higher incidence of certain AEs in males.

Introduction: The risk of HCC is twice as high in diabetic patients compared to non-diabetic ones, suggesting that diabetes advances carcinogenesis in the liver through a variety of mechanisms. Sodium-glucose cotransporter 2 inhibitors (SGLT2i) have been shown to improve liver outcomes, emerging as promising agents to treat hepatocellular carcinoma (HCC) in patients with type 2 diabetes mellitus (T2DM).

Methods: We searched PubMed and Scopus databases for articles presenting an association between SGLT2is and HCC to explore the putative mechanisms of action underlying the anti-proliferative activity of SGLT2is.

Results: A total of 24 articles were selected for inclusion, of which 14 were preclinical and 10 were clinical. Preclinical studies were mainly focused on canagliflozin, used alone or in combination with other drugs.

Conclusions: Overall, canagliflozin had a negative effect on HCC cell proliferation by interfering with glucose-dependent and independent metabolic pathways, negatively impacting angiogenesis, and inducing apoptosis in in-vitro cell models. In-vivo, a protective effect on hepatic steatosis and fibrosis and HCC development has been reported. Human studies showed a lower risk of developing HCC in patients on SGLT2is. However, this is supported by retrospective cohort studies. Clinical trials are needed to confirm the causal relationship between SGLT2i administration and HCC development.

Background: Radium-223 (Ra-223) received U.S. Food and Drug Administration (FDA) approval for treating castration-resistant prostate cancer with symptomatic bone metastases, excluding visceral metastases. Despite this, the safety profile of Ra-223 in large-scale, population-based use still needs to be explored.

Research design and methods: This research assesses the side effects of Ra-223 by analyzing reports of adverse events (AEs) from the FDA's Adverse Event Reporting System (FAERS) database. Four sequential analysis strategies were employed to assess the significance of these AEs.

Results: In total, 4,228 Ra-223-related AE reports were identified in the FAERS database. These Ra-223-induced AEs were observed in 26 target system organ classes (SOCs). 124 Ra-223-induced AEs were detected in 26 SOCs, predominantly affecting the blood and lymphatic systems. Other notable AEs included diarrhea, nausea, asthenia, fatigue, malaise, and decreased appetite, some of which were not previously documented in product specifications. The median time to onset of AEs was 56 days (Interquartile Range 26-103 days), with the majority of AEs occurring within the first three months after Ra-223 administration.

Conclusions: Our findings align with clinical observations and suggest potential new and unexpected AEs related to Ra-223, underscoring the need for prospective clinical studies to confirm these results and clarify their relationships. These insights provide valuable evidence for further safety studies and the rational use of Ra-223.

Background: Drug-induced nephrolithiasis is a recognized complication in clinical practice. The objective of this study is to identify drugs that are significantly associated with an increased risk of inducing nephrolithiasis based on the Food and Drug Administration (FDA) Adverse Event Reporting System (FAERS).

Research design and methods: We collected adverse event reports associated with drug-induced nephrolithiasis from the first quarter of 2004 (2004 Q1) to the fourth quarter of 2023 (2023 Q4) in the FAERS database. Subsequently, we applied 4 disproportionality algorithms to evaluate the connection between drugs and nephrolithiasis.

Results: A total of 32,788 adverse event reports related to nephrolithiasis with primary suspected drugs were identified. The 50 drugs with the highest frequency and the 40 drugs with the strongest signal were identified and counted. The most frequently occurring drug was adalimumab, while the antiretroviral drug indinavir exhibited the strongest signal intensity. The labels for many of these drugs did not mention the risk of nephrolithiasis.

Conclusions: This comprehensive pharmacovigilance study has revealed many drugs potentially associated with an increased risk of nephrolithiasis. Notably, vigilant surveillance for nephrolithiasis risk while using these drugs is crucial in clinical practice.

Introduction: Biliary tract cancer (BTC) originates from the biliary epithelium of the small ducts within the liver (intrahepatic cholangiocarcinoma, IHCC), the main ducts of the hilum (extrahepatic cholangiocarcinoma, EHCC), or in the gallbladder (gallbladder cancer, GC). Due to presentation with nonspecific symptoms as well as absence of screening, most patients present with advanced disease and unfavorable prognosis.

Areas covered: The ABC-02 trial established the current first-line chemotherapy with gemcitabine/platinum for advanced BTC in 2010. Since then, multiple therapies have become available exploring different targetable alterations, emphasizing the importance of molecular profiling in all patients with BTC as well as understanding the distinct toxicity profile associated with these therapies. Besides chemotherapy, immunotherapy as well as targeted therapies for FGFR2, IDH1 and HER2 will be discussed in this manuscript. We performed a non-systematic review, largely based on high-quality articles on the topic of interest with no predefined protocol.

Expert opinion: The primary objective of this manuscript is to conduct a thorough review of diverse aspects related to the safety of systemic treatment in BTC. As the benefit of these therapies depends on compliance and/or tolerance, the authors aim to discuss different toxicity profiles and to provide insights into strategies for overcoming them.

Objectives: Analyze hematopoietic ADR signals of PARP inhibitors (Olaparib, Niraparib, Rucaparib, Talazoparib) using FAERS data to inform clinical practice.

Methods: Extracted ASCII data for these drugs from Q1 2019 to Q2 2024. Employed SMQ and PT for standardization. Screened ADR signals via ROR, PRR, and MHRA method, comparing SMQ ratios.

Results: Hematopoietic ADRs peaked within 30 days post-treatment, with cytopenia and leukopenia most prevalent. Niraparib showed the highest adverse event count and signal intensity. Olaparib and Talazoparib also indicated strong hematotoxicity.

Conclusion: PARP inhibitors vary in ADR incidence and duration, necessitating personalized treatment plans for optimized safety and rational use.

Background: In recent years, β-blockers such as metoprolol have been upgraded to first-line antihypertensive drugs. However, metoprolol demonstrates poor prognosis effects on diseases such as stroke. Further clinical application may expand the possibility of its related adverse reactions. Currently, there is a lack of comprehensive research on the overall safety of metoprolol.

Research design and methods: Statistical analysis and signal mining were conducted on adverse event reports related to metoprolol obtained from the FAERS database. Signal mining was conducted using the proportional reporting ratio, the report margin method, the bayesian confidence propagation neural network, and empirical Bayesian geometric mean in the measures of disproportionality to detect potential adverse reaction signals.

Results: The results showed 16,853 reports related to metoprolol use, identifying 506 preferred terms (PTs) covering 23 system organ classes (SOCs). In addition, some new potential adverse reactions appeared among the top 30 PTs ranked by signal strength, such as 'orthostatic intolerance' (IC025 = 3.00), 'trigemino-cardiac reflex' (IC025 = 4.30), 'decorticate posture' (IC025 = 3.34), etc. Notably, there was a strong association between 'suspected suicide' (IC025 = 5.59) and the drug signal.

Conclusions: This study identified unexpected signals of serious adverse reactions, suggesting the importance of continuous post-marketing surveillance of metoprolol to understand its potential risks.