Background: Skin adverse events of apalutamide pose a major challenge to its clinical use, particularly the severe and difficult to identify toxic epidermal necrolysis. For the purpose of providing the basis for the clinical monitoring of the administration of apalutamide and further research. This study examined the pathways of apalutamide and Stephen Johnson Syndrome/Toxic Epidermal Necrolysis using network pharmacology and data mining tools to analyze skin adverse events.Methods: Using the Information Component method and the Reporting Odds Ratio, the relationship between apalutamide and skin adverse events was evaluated. Molecular docking was utilized to explore the potential mechanism of apalutamide and Stephen Johnson Syndrome/toxic epidermal necrolysis.Results: With a median time to onset of all skin adverse events of 55 days, a total of 21 skin-related adverse events were found. Low body weight and advanced age may be major hazards for skin adverse events with apalutamide. The results showed a substantial association between apalutamide and Stephen Johnson Syndrome/toxic epidermal necrolysis, and the mechanism behind this association may be the binding of apalutamide to JAK1 and JAK2.Conclusion: Special attention is recommended for skin adverse events when using apalutamide, especially for rapidly progressing and severe adverse events. To confirm the connection between the triad of Janus kinase, apalutamide, and skin adverse events, further research is required in the future.

Mining and updating the post-marketing safety signals of esketamine nasal spray for better identification of adverse drug event (ADE) signals and medication monitoring during clinical use to ensure patient medication safety. Downloading data from the US Food and Drug Administration Adverse Event Reporting System from Q1 2019 to Q2 2023, the reporting odds ratio, proportional reporting ratio, Multi-item Gamma Poisson Shrinker, and Bayesian Confidence Propagation Neural Network methods of the disproportionality method were used to mine and analyze ADEs, and finally to screen for signals of ADEs with esketamine nasal spray as the primary suspected drug. The Preferred Terminology of the Medical Dictionary of Regulatory Activities (version 26.0) was used to standardize the description of ADEs and to attribute ADEs to the System Organ Classification. A total of 5132 ADEs reports of esketamine nasal spray as the primary suspected drug were obtained from the Food and Drug Administration Adverse Event Reporting System. The most frequently observed ADEs are dissociation, sedation, and hypertension, while some new rare signals have been detected, such as interstitial cystitis, substance abuse, and drug diversion. The present study identified significant new ADEs signals for esketamine nasal spray, which may provide a source for healthcare professionals to assess patients’ symptoms and risk identification.

Object: Based on the best available evidence, rapid health technology was used to assess 4 CDK4/6 inhibitors approved for marketing in China. This assessment aims to provide a reference basis for the selection of drugs by medical institutions in China and to promote the rational use of drugs in the clinic. Methods: Depending on the Rapid Guidelines for Drug Evaluation and Selection in Chinese Medical Institutions (the Second Edition), a percentage quantitative scoring approach was used to objectively score the pharmacological properties, efficacy, safety, economy, and other attributes of CDK4/6 inhibitors. Results: The composite score rankings were, in descending order, 78.09 points for abemaciclib, 78.04 points for palbociclib, 72.15 points for dalpiciclib, and 69.24 points for ribociclib by integrating the result of the 5 dimensions. Conclusion: Until the clinical studies, guideline recommendations, prices, and many other aspects of this assessment are updated, abemaciclib and palbociclib, which have the top 2 scores, can be used as a priority recommendation for Chinese medical institutions to select CDK4/6 inhibitors and optimize the use of the drug catalog based on the scoring results of this assessment.

Objective: The combination of second-generation androgen receptor (AR) antagonists with androgen deprivation therapy (ADT) has shown good efficacy and safety in advanced prostate cancer. This study aims to evaluate the cost-effectiveness of three second-generation AR antagonists in the treatment of metastatic hormone-sensitive prostate cancer (mHSPC) in China, providing pharmacoeconomic evidence for clinical drug selection.Methods: A Markov model was constructed based on data from the ARCHES, TITAN, and ARANOTE phase III clinical trials, with a 28-day cycle period. Direct medical costs and quality-adjusted life years (QALYs) were simulated over a 15-year horizon. The incremental cost-effectiveness ratio (ICER) was used as the primary outcome, and a willingness-to-pay (WTP) threshold of three times the 2024 per capita GDP of China was set for cost-utility analysis. Sensitivity analysis was conducted to validate the model’s influencing factors and the robustness of the results.Results: The cumulative cost of the apalutamide regimen was ¥776,807, resulting in 4.95 QALYs. Compared to apalutamide, the ICER for enzalutamide was ¥643,309/QALY, while for darolutamide, the ICER was -¥40,625/QALY.Conclusion: For Chinese mHSPC patients, darolutamide is the most cost-effective treatment at a WTP threshold of ¥287,391/QALY, followed by apalutamide, with enzalutamide being less favorable.