Therapeutic Advances in Drug Safety最新文献

Background: With the increasing prescription of reslizumab for severe asthma with an eosinophilic phenotype, a real-world pharmacovigilance analysis of reslizumab is urgently required to detect potential unreported adverse events (AEs) in clinical practice.

Objectives: We aimed to provide a comprehensive evaluation of reslizumab-related AEs in the real world.

Design: Disproportionality analysis based on the FDA Adverse Event Reporting System (FAERS) database.

Methods: Reslizumab-related AEs between the second quarter of 2016 and the fourth quarter of 2022 from the FAERS database were obtained. A disproportionality analysis was performed to evaluate the safety profile of reslizumab using the reporting odds ratio.

Results: A total of 10,450,353 reports were collected from the FAERS database. Of the 403 reslizumab-related AEs, 42 distinct AEs were identified with positive signals. The most common AEs including dyspnea and oropharyngeal pain were identified, consistent with the instruction and clinical studies. Unexpected AEs of disproportionality such as bronchospasm and chest pain were also observed. Drug ineffective was identified as a noteworthy concern that accounted for 13.90% (56/403) of the overall reslizumab-related reports.

Conclusion: While reslizumab offered a promising treatment option for severe eosinophilic asthma, more attention should be paid to the common AEs and new unexpected AEs. Based on the current findings of signal detection, further prospective studies are needed for the next signal validation and confirmation.

Objectives: This pharmacovigilance analysis was conducted to assess the safety signals of FMS-related tyrosine kinase 3 (FLT3) inhibitors in a real-world setting using the United States Food and Drug Administration Adverse Event Reporting System (FAERS).

Design: We analyzed adverse event (AE) reports related to FLT3 inhibitors submitted to the FAERS database from the first quarter of 2015 to the fourth quarter of 2022. Disproportionality analysis was used to identify AEs of FLT3 inhibitors in the FAERS database.

Results: A total of 55,393 AE reports were identified, of which 5938, 44,013, and 5442 were attributed to midostaurin, sorafenib, and gilteritinib, respectively, as primary suspects. Compared to the full database, significant safety signals at the system organ class level were observed for midostaurin (blood and lymphatic system disorders and hepatobiliary disorders), sorafenib (skin and subcutaneous tissue disorders and hepatobiliary disorders), and gilteritinib (investigations, blood and lymphatic system disorders, infections and infestations, and hepatobiliary disorders). All the drugs studied were associated with hepatobiliary disorders. The most prominent AEs associated with midostaurin, sorafenib, and gilteritinib were cytopenia, palmar-plantar erythrodysesthesia syndrome, and increased blast cell count, respectively. Compared with chemotherapy, midostaurin and gilteritinib showed a higher risk of electrocardiogram QT prolongation, gastrointestinal hemorrhage, cerebral hemorrhage, and increased white blood cell count. Gilteritinib had the highest overall death percentage (30.28%), whereas sorafenib had the lowest (23.06%).

Conclusion: Mining AE signals using the FAERS database provides a method for analyzing the safety of FLT3 inhibitors in post-marketing. We found several significant AE signals that corresponded to previous studies; however, some AE signals were not mentioned in the drug instructions. Our study could provide a direction for follow-up real-world studies to verify the results further.

Non-cystic fibrosis bronchiectasis is a long-term lung disease characterised by abnormal dilatation of the bronchi, with patients experiencing chronic productive cough and recurrent exacerbations. Currently, there are no licensed drugs for use in bronchiectasis while clinical trials have been conducted to either test new drugs or repurpose existing ones. These drugs target the underlying pathophysiology of bronchiectasis which is known to include infection, inflammation, mucus hypersecretion and retention. Most of the drugs used in daily clinical practice for bronchiectasis are off-label with no randomised trials exploring their safety. This review aims at exploring the safety profile of drugs frequently used in clinical practice to manage bronchiectasis, including antibiotics (e.g. macrolides, aminoglycosides, polymyxins, fluoroquinolones, aztreonam), mucoactive therapy (e.g. hypertonic saline, mannitol, DNase and carbocisteine), anti-inflammatory therapy (inhaled corticosteroids) and drugs currently in development for use in bronchiectasis (e.g. brensocatib, benralizumab and itepekimab).

Background: Cyclin-dependent kinases 4 and 6 (CDK4/6) inhibitors are targeted therapies designed to selectively block CDK4/6, crucial regulators of the cell cycle. These inhibitors play a pivotal role in restoring cell cycle control, particularly in breast cancer cases marked by abnormal CDK regulation, ultimately inhibiting uncontrolled cell division and tumor growth.

Objectives: This analysis aimed to comprehensively examine adverse effects in CDK4/6 inhibitors using the United States Food and Drug Administration (FDA) Adverse Event Reporting System (FAERS) database.

Design: Disproportionality analysis was conducted to analyze the adverse event (AE) reports related to CDK4/6 inhibitor submitted to the FAERS database.

Methods: We collected AE reports regarding palbociclib, ribociclib, abemaciclib, trilaciclib, and dalpiciclib submitted to the FAERS from 2015Q1 to 2023Q1. We used the system organ class and the Standardized MedDRA Query to perform a comprehensive search for AEs at the preferred term (PT) level, using case reports as our data source. After removing duplicate reports, we performed disproportionality analysis and sensitivity analysis to identify safety signals.

Results: A total of 85,635 reports encompassing 280,211 AEs were extracted for analysis. Among 3681 scrutinized PTs, approximately 484 were detected as statistically significant signals associated with CDK4/6 inhibitors. It was noteworthy that palbociclib and ribociclib had comparable safety profiles, whereas abemaciclib exhibited distinctive safety patterns. Notably, our analysis found novel safety signals linked to CDK4/6 inhibitors, including nail-related disorders such as onychoclasis, nail disorder, and nail discoloration, and psychiatric concerns, including eating disorders and emotional disorder.

Conclusion: Overall, the present study identified several new safety signals of CDK4/6 inhibitors, as well as differences among various drugs within the CDK4/6 category, through the use of the FDA FAERS, which deserve more careful monitoring in the clinic.

Background: Linezolid-induced anemia (LI-AN) is a severe adverse reaction, but risk factors of the LI-AN for elderly patients have not been established.

Objectives: The objective of this study was to develop a nomogram capable of predicting LI-AN in elderly patients.

Design: This is a retrospective study to develop and validate a nomogram for anemia prediction in elderly patients treated with linezolid.

Methods: We retrospectively screened elderly patients treated with linezolid at Inner Mongolia People's Hospital from January 2020 to December 2023 and validated our findings using the MIMIC-IV 2.2 database. Anemia was defined as hemoglobin reduction to 75% of baseline value. Univariate and multivariable logistic regression models were used to identify predictors and construct the nomogram, which was evaluated using receiver operating characteristic (ROC) curve analysis, calibration plot, and decision curve analysis.

Results: A total of 231 patients were enrolled in this study. The training set comprised 151 individuals, and anemia occurred in 28 cases (18.54%). In the external validation set of 80 individuals, 26 (32.5%) were diagnosed with anemia. The predictors included duration of linezolid therapy, patient estimated glomerular filtration rate value, and sequential organ failure assessment score ⩾2. The ROC curve for the training set was 0.830 (95% CI: 0.750-0.910), while a similar ROC curve of 0.743 (95% CI: 0.621-0.865) was obtained for the validation set. The calibration curve demonstrated good correlation between predicted and observed results, indicating that this study effectively predicts risk factors associated with LI-AN in elderly patients.

Conclusion: The developed prediction model can provide valuable guidance for clinicians to prevent anemia and facilitate rational linezolid use in elderly patients.