Expert Opinion on Drug Safety最新文献

Background: Tafasitamab is the first anti-CD19 monoclonal antibody approved for relapsed/refractory diffuse large B-cell lymphoma patients ineligible for autologous stem cell transplantation. The study was designed to evaluate tafasitamab-associated adverse events (AEs) by data mining the United States Food and Drug Administration Adverse Event Reporting System (FAERS).

Research design and methods: A disproportionality analysis was performed to assess the safety profile of tafasitamab based on the reports from the FAERS database between 2020Q3 and 2023Q3. Proportional reporting ratio (PRR) and empirical Bayesian geometric mean (EBGM) were used to identify the signals of AEs in patients receiving tafasitamab.

Results: A total of 529 reports with tafasitamab as the primary suspect drug were collected, including 1,262 AEs. Of these, 28 repeated AEs were identified using two algorithms. After excluding events unrelated to drug therapy, the top five repeated AEs by intensity ranking were cytopenia, immunosuppression, neutropenic sepsis, blood lactate dehydrogenase increased, and hematotoxicity. Unexpected significant AEs included polyneuropathy, splenomegaly, hemophagocytic lymphohistiocytosis, hypercalcemia, and ascites.

Conclusions: This study provides additional evidence for risk identification of tafasitamab in the real world, which could help clinicians and pharmacists increase vigilance and improve the safety of tafasitamab in clinical practice.

Background: Ustekinumab is a fully human interleukin-12/23 (p40) inhibitor used to treat immune-mediated diseases. However, the limitations of clinical trials and the expanding target population necessitate an update on the ustekinumab-associated adverse events (AEs). We conducted signal mining for ustekinumab-related AEs using the United States Food and Drug Administration Adverse Event Reporting System (FAERS).

Research design and methods: AE reports were collected from 2009 Q3 to 2024 Q1. Four disproportionality analysis algorithms - reporting odds ratio, medicines and healthcare products regulatory agency, Bayesian confidence propagation neural network, and multi-item gamma Poisson shrinker - were used to quantify the signals of ustekinumab.

Results: During this period 69,345 AE reports associated with ustekinumab were collected, and ustekinumab was identified as the primary suspect. Overall, 319 signals involving 15 system organ classes were identified, and 111 signals had a medium or strong value for IC₀₂₅. Of them, 67 were classified as important medical events. Squamous cell carcinoma, pertussis, vulval abscess, breast abscess, and fistula exhibited higher signal intensities.

Conclusions: Our study identified the risk signals for ustekinumab using real-world data and provides further evidence to support its rational use. Due to the limitations of FAERS, further studies are warranted to verify these findings.

Background: Anti-herpesvirus drug safety profiles have not been systematically compared. Understanding variations in adverse events (AEs) could provide reference for rational clinical use.

Methods: We collected data on acyclovir, ganciclovir, valaciclovir, and foscarnet from the FDA Adverse Event Reporting System (FAERS) database from Q1 2004 to Q3 2023. Disproportionality analyses were conducted to evaluate the risk of AEs.

Results: All drugs exhibited significant associations with hematotoxicity, with ganciclovir and foscarnet being more myelosuppressive. The correlation with renal impairment ranked as follows: foscarnet, ganciclovir, valaciclovir, and acyclovir (ROR = 16.72, 7.06, 3.51, and 2.02, respectively). Regarding hepatotoxicity, ganciclovir was associated with acute-on-chronic liver failure (ROR = 52.83), and foscarnet was associated with fulminant hepatitis (ROR = 49.91). In the nervous system, acyclovir showed the highest intensity of neurotoxicity (ROR = 14.95). Valaciclovir ranked first in toxic encephalopathy (ROR = 64.70). Foscarnet showed the highest intensity of status epilepticus (ROR = 6.45). Besides, acyclovir showed the strongest association with severe cutaneous adverse reactions (SCARs).

Conclusions: Our study revealed differences in safety profiles of four anti-herpesvirus medications. Ganciclovir exhibited the highest risk of hematotoxicity but appeared relatively safe in seizures and SCARs. Foscarnet was more likely to induce nephrotoxicity, seizures, and electrolyte imbalances than others. Acyclovir and valaciclovir were strongly associated with plasmacytosis, neurotoxicity, and SCARs.

Background: This study analyzed adverse events (AEs) associated with inclisiran using the FDA's Adverse Event Reporting System (FAERS) to detect and characterize relevant safety signals.

Methods: We retrospectively extracted AE reports from the FAERS database spanning Q1 2022 to Q2 2024. Four disproportionality analysis algorithms were employed to identify AE signals for inclisiran, with subsequent comparisons made to PCSK9 monoclonal antibodies (alirocumab/evolocumab). Additionally, we examined the characteristics and onset timing of inclisiran-related AE.

Results: A total of 4,122 reports of inclisiran as the 'primary suspected'. Compared with all other drugs, the most significant system organ class (SOC) was 'musculoskeletal and connective tissue disorders' (ROR = 3.64, PRR = 3.19) and the most common SOC was 'general disorders and administration site conditions' (n = 2,769). These two SOCs were more strongly with inclisiran than evolocumab. At the preferred term level, strong signals were detected for cellulitis gangrenous (ROR = 101.29, PRR = 101.27, IC = 6.54, EBGM = 92.91) and bladder discomfort (ROR = 12.61, PRR = 12.61, IC = 3.64, EBGM = 12.48). The median onset time for inclisiran-related AEs was 43 days (interquartile range: 7-99 days).

Conclusions: This study enhanced our understanding of AEs to inclisiran. Future research on its long-term real-world use will offer insights into its safety.

Introduction: Percutaneous nephrolithotomy (PCNL) is a widely used surgical procedure for treating large and complex kidney stones. Although effective, it carries risks of complications such as bleeding, infection, and injury to adjacent structures. Optimization of procedural techniques and perioperative care can help minimize these risks.

Areas covered: This review examines key pre- and post-operative safety considerations for PCNL patients. Topics include pre-operative imaging, patient positioning, puncture techniques, tract dilation, postoperative drainage, and complication management. The literature search involved analyzing recent studies and clinical guidelines to identify best practices. The search was conducted in several databases, including PubMed, Embase, the Cochrane Library and clinical guidelines. Training modalities for improving procedural skills are discussed.

Expert opinion: Improving the safety of PCNL requires a combination of meticulous surgical technique, proper patient selection, and adherence to standardized protocols. Continuous skill development and technological advancements will further improve patient outcomes.

Objective: This study analyzed the signal mining of adverse events caused by finerenone based on the US Food and Drug Administration Adverse Event Reporting System (FAERS) and evaluated the drug's safety to provide a reference for the safe administration of this medication in medical institutions.

Methods: FAERS data from the third quarter of 2021 to the fourth quarter of 2023 were used, and the adverse event codes of the Medical Dictionary for Regulatory Activities were compared. After the data were processed, adverse event reports that featured finerenone as the most suspected drug were extracted.

Results: A total of 905 reported cases of adverse events including finerenone as the first suspected drug were extracted. The ratio of male to female patients was 1.25, and most were aged 65-85 years (30.1%). The adverse events that were reported more frequently with positive signals were decreased glomerular filtration rate, hyperkalemia, increased blood creatinine, and dizziness. The adverse events that were concentrated on in investigations were metabolism and nutrition disorders and diseases of the renal and urinary system.

Conclusions: Our study identified significant novel adverse events (AEs) signals for finerenone that could provide support for clinical monitoring of and risk identification for finerenone.

Background: Dapagliflozin prevents myocardial dysfunction in chronic kidney disease patients regardless of residual kidney function. We hypothesized that this effect is extensible also to patients on dialysis.

Research design and methods: The DARE-ESKD-2 is an ongoing, single-center, open-label randomized clinical trial designed to determine the effects of adding dapagliflozin to standard treatment on myocardial function and structure. Eligible patients were adults on a regular dialysis scheme for more than 3 months. Pregnancy, liver failure, allergy to the investigational drug, and prior use of SGLT2i were exclusion criteria. Participants were randomized in a 1:1 ratio to dapagliflozin or standard treatment groups for 24-weeks. The primary goal is to compare the change in NT-proBNP levels between study arms, and secondary goals include comparing the between-group difference in left ventricle global longitudinal strain, indexed mass, ejection fraction, and E/e` ratio, and on symptoms scale and 6-minute walk test distance. An exploratory analysis will evaluate changes in body composition and bone densitometry.

Results: The trial has finished the enrollment of 80 patients, who are currently being followed-up.

Conclusions: This trial will provide novel data on myocardial effects of SGLT2i in dialysis recipients. Results from this study may provide evidence to support SGLT2i use in ESKD.

Objective: Utilizing the FAERS database, this study aims to analyze the ADE signals of sacituzumab govitecan to provide references for clinical safety.

Methods: By searching the US FAERS database, we applied Reporting Odds Ratio (ROR) and Proportional Reporting Ratio (PRR) methods to analyze ADE reports for sacituzumab govitecan from Q2 2020 to Q4 2023, covering 15 quarters.

Results: The total number of reports with sacituzumab govitecan as the first suspicion was 2854. A total of 139 signals involving 26 SOCs were obtained. The most reported were general disorders and administration site conditions (2,307 cases, 25.66%), followed by gastrointestinal disorders (1,125 cases, 12.52%), and investigations (810 cases, 9.01%). Frequent ADEs included sepsis and COVID-19 were not listed in the prescribing information. The signal strength analysis highlighted conditions like cholestasis and epilepsy not mentioned in the prescribing information. Furthermore, an analysis of influencing factors revealed differences in infections and infestations by gender and nationality (p < 0.05), and in gastrointestinal disorders and blood and lymphatic system disorders by gender, treatment duration, and nationality (p < 0.05).

Conclusions: Common ADEs generally correspond with the prescribing information. Clinicians should be vigilant regarding unlisted ADEs about sacituzumab govitecan, and close monitoring of laboratory indicators ensure patient medication safety.

Introduction: Insulin remains the mainstay of diabetes management. Once weekly insulins (OWI) being investigated as viable options for both type 1 and type 2 diabetes. Less frequent dosing and better pharmacokinetic profile with these products hold the promise for improved patient adherence and enhanced efficacy in everyday practice.

Areas covered: We conducted a biomedical literature review of the PubMed database from 2009 to 2025. This narrative review summarizes the characteristics, advantages, and drawbacks of the two OWI products on the market and in development, namely insulin icodec and insulin efsitora. We review the published data with an emphasis on the safety of these when compared with daily long-acting insulin in insulin-treated and insulin-naïve patients with diabetes.

Expert opinion: The available data for OWI thus far points to similar adherence, acceptability, and efficacy when compared to once-daily insulin. OWI use was associated with comparable lowering of glycosylated hemoglobin and achievement of glycemic targets, potentially widening the treatment options for individuals with diabetes. However, increased risks of hypoglycemia and weight gain were seen in some studies. The clinical concerns regarding hypoglycemia led the U.S. regulatory agency to vote against recommending approval of icodec for use in patients with type 1 diabetes.

Background and aims: Ciprofol (HSK3486), a novel intravenous anesthetic with a chemical structure similar to propofol, is not inferior to propofol in terms of its effectiveness. We compared the effects of ciprofol and propofol on dreams and emotional states in patients following painless gastroscopy.

Research design and methods: This was a single-center, randomized controlled trial. The primary outcome was the proportion of positive dreams during sedation.

Results: A total of 110 outpatients were included, with 55 in each group. The proportion of positive dreams among dreamers was significantly greater in the propofol group than in the ciprofol group (60.9% vs 20.0%; p = 0.020). Additionally, the propofol group exhibited significantly higher positive emotion scores compared to the ciprofol group (19 [15,25] vs 17 [12,21]; p = 0.021). No significant differences were observed in vital signs, BIS values, or satisfaction with the procedure between the two groups. As for the adverse drug reactions, the incidence of injection pain of propofol was significantly higher than that of ciprofol (12.7% vs 0%; p = 0.013).

Conclusions: Compared to propofol, ciprofol demonstrated a weaker capacity to induce positive dreams and emotions during painless gastroscopy. However, this does not impact patient satisfaction with the procedure.

Clinical trial registration: www.chictr.org.cn; identifier: ChiCTR2400082655.