Stud Health Technol Inform. 2025 May 15;327:892-893. doi: 10.3233/SHTI250495.

ABSTRACT

Monitoring adverse drug events (ADEs) is critical for pharmacovigilance and patient safety. However, identifying ADEs remains challenging, as suspected or confirmed side effects are often documented solely in the unstructured text of electronic health records (EHRs). Manually reviewing clinical notes to detect ADEs is labor-intensive and time-consuming, highlighting the need for automated methods capable of analyzing and extracting ADE-related information from clinical documentation. In this short communication, we describe our ongoing research on fine-tuning and evaluating a large language model (LLM) for the detection of ADEs in clinical notes. Preliminary descriptive result of this study indicates that ADEs are poorly documented in discharge notes, with less than 15% explicitly linking ADEs to specific drugs, which highlights the need for improved reporting practices.

PMID:40380603 | DOI:10.3233/SHTI250495

Stud Health Technol Inform. 2025 May 15;327:778-782. doi: 10.3233/SHTI250465.

ABSTRACT

Adverse drug event (ADE) detection in social media texts poses significant challenges due to the informal nature of the text and the limited availability of annotations. The scarcity of ADE named entity recognition (NER) datasets for social media hinders the development of robust ADE detection models for this type of corpus. In this paper, we leveraged the generative capabilities of large language models (LLMs) to create synthetic data, addressing this dataset gap. Specifically, we generated 17,000 tweets with ADE annotations and pre-trained NER models on this synthetic data. Our evaluations on an out-of-sample collection of 915 manually annotated tweets revealed that these models outperform state-of-the-art lexico-based and massively pre-trained open NER models. We also show that fine-tuning our synthetically pre-trained models on human-annotated data surpasses the current state-of-the-art in ADE detection on tweets. These findings suggest that synthetic data generated by LLMs can enhance ADE detection performance, offering a promising avenue to explore in response to the scarcity of annotated ADE datasets. The synthetic dataset is available at https://huggingface.co/datasets/anthonyyazdaniml/synthetic-ner-ade-tweets-v1.

PMID:40380573 | DOI:10.3233/SHTI250465

Stud Health Technol Inform. 2025 May 15;327:245-246. doi: 10.3233/SHTI250320.

ABSTRACT

One approach to preventing adverse drug events (ADEs), such as harmful drug interactions, is the implementation of clinical decision support systems (CDSS). In an ongoing project, we are investigating the accuracy of the rule-based CDSS currently utilized in Swedish healthcare for predicting ADEs and exploring whether machine learning (ML) can improve these predictions. By analyzing real-world healthcare data from a Swedish region spanning a 10-year period, we show that ML has potential to improve ADE predictions compared to existing rule-based CDSS.

PMID:40380432 | DOI:10.3233/SHTI250320

J Pharmacokinet Pharmacodyn. 2025 May 16;52(3):32. doi: 10.1007/s10928-025-09979-2.

ABSTRACT

The assessment of drug-induced QT interval prolongation and associated proarrhythmic risks, such as Torsades de Pointes (TdP), has evolved significantly over the past decades. This review traces the development of nonclinical QT evaluation, highlighting key milestones and innovations that have shaped current practices in cardiac safety assessment. The emergence of regulatory guidelines, including International Council for Harmonization of Technical Requirements for Pharmaceuticals for Human Use (ICH) S7B, established a nonclinical framework for evaluating drug effects on cardiac repolarization, addressing concerns raised by drug withdrawals in the 1990s. Advances in in vitro, in vivo, and in silico models have enhanced the predictive accuracy of nonclinical studies, with the hERG assay and telemetry-based animal models becoming gold standards. Recent initiatives, such as the Comprehensive in vitro Proarrhythmia Assay (CiPA) and the Japan iPS Cardiac Safety Assessment (JiCSA), emphasize integrating mechanistic insights from human-derived cardiomyocyte models and computational approaches to refine risk predictions. The 2020s mark a shift toward integrated nonclinical-clinical risk assessments, as exemplified by the ICH E14/S7B Questions and Answers. These highlight the need of best practices for study design, data analysis, and interpretation to support regulatory decision-making. Furthermore, the adoption of New Approach Methodologies (NAMs) and reinforced adherence to 3Rs principles (Reduce, Refine, Replace) reflect a commitment to ethical and innovative safety science. This review underscores the importance of harmonized and translational approaches in cardiac safety evaluation, providing a foundation for advancing drug development while safeguarding patient safety. Future directions include further integration of advanced methodologies and regulatory harmonization to streamline nonclinical and clinical risk assessments.

PMID:40379846 | DOI:10.1007/s10928-025-09979-2

J Immunother Cancer. 2025 May 15;13(5):e011312. doi: 10.1136/jitc-2024-011312.

ABSTRACT

Immune-related adverse events (irAEs) can cause severe morbidity and mortality, and they impair treatment with immune checkpoint inhibitors (ICI). Risk factors for irAEs are not well understood.We observed cases of patients having tumor deposits in their liver and lung during a workup of irAEs, which led us to hypothesize that the presence of tumor in an organ would increase the odds of developing severe irAEs in that organ. We then performed a retrospective cohort study that included patients who received an ICI for the treatment of cancer and were hospitalized between February 2011 and November 2021 at the Massachusetts General Hospital.We reviewed 384 patients hospitalized with concern for any irAE. A clinical diagnosis of ICI-related hepatitis occurred in 18% of patients with liver tumor deposits versus 8% of those without (OR 2.23, 95% CI (1.10 to 4.43), p=0.02). ICI-related pneumonitis occurred in 10% of patients with lung tumor deposits versus 4.4% of those without (OR 2.45, 95% CI (1.06 to 6.36), p=0.047). A combined analysis for liver and lung lesions demonstrated that the presence of tumor deposits in an organ increased the odds of having an irAE in that organ by over twofold (OR 2.31, 95% CI (1.34 to 3.99), p=0.002).Our results suggest that the presence of tumor deposits may represent a novel risk factor for severe irAEs in that organ.

PMID:40379269 | DOI:10.1136/jitc-2024-011312

J Control Release. 2025 May 14:113844. doi: 10.1016/j.jconrel.2025.113844. Online ahead of print.

ABSTRACT

Thoracic aortic dissection (TAD) is a life-threatening cardiovascular disease characterized by rapid progression and high morbidity. Current efforts to develop effective treatment strategies focus on targeting apoptotic aortic endothelial cells and mitigating inflammation. Here, inspired by the inflammation-neutralizing capacity of functional cells, we present multifunctional biomimetic nanovesicles (MM-LPs) co-assembled from macrophage membranes and synthetic lipids for the targeted delivery of Senkyunolide I (SEI) in TAD treatment. The integration of macrophage membranes endows MM-LPs with the ability to selectively target activated vascular endothelial cells (VECs) while adsorbing proinflammatory cytokines to suppress inflammation. Additionally, these nanoparticles enable the controlled release of SEI, leading to significant anti-apoptotic effects. Leveraging these advantages, MM-LPs effectively mitigated VEC activation, reduced apoptosis, and prevented disease progression and rupture in a BAPN-induced mouse model of TAD. Furthermore, this system significantly reduced SEI-associated toxicity and adverse effects on the liver and kidneys. These findings highlight the potential of combining natural macrophage membranes with synthetic lipids to develop a multifunctional biomimetic drug delivery system for treating VEC dysfunction while minimizing drug-related side effects.

PMID:40379216 | DOI:10.1016/j.jconrel.2025.113844

PLoS One. 2025 May 16;20(5):e0321785. doi: 10.1371/journal.pone.0321785. eCollection 2025.

ABSTRACT

BACKGROUND: In 2017, reports of adverse drug reactions worldwide reached an estimated 35 million.Chemotherapeutic agents were one of the most often implicated pharmacological classes in inducing adverse drug reactions. Adverse drug reactions increase the overall expense and mortality. Adverse drug reactions increase morbidity, mortality, hospitalization rate and financial expenses. Therefore, this study intended to assess chemotherapy-related adverse drug reactions and associated factors among adult cancer patients.

PATIENTS AND METHOD: A facility-based prospective observational study was conducted from July 2022 to October 2022 at Jimma Medical Center's oncology unit. A standard data collection tool (Naranjo's algorithm, modified Hartwig's severity scale, and modified Schumock-Thornton criteria) was used for assessment of causality, severity, and preventability of adverse reactions, respectively. Socio-demographic profile and any adverse drug reactions reported were collected separately. The data was collected by one pharmacist and two nurses after giving training. Data was entered into Epidata version 4.6.0 and analyzed by SPSS version 25. Bivariate and multivariable logistic regression was conducted to identify independent predictors of the pattern of adverse drug reaction occurrence. A P-value of 0.05 was taken as statistically significant.

RESULT: Out of 154 patients enrolled in the study, 66.2% were female. The mean age of patients was 41.20 ± 13.54 years. From the total, 98 (63.6%) cases developed a total of 198 adverse drug reactions. Out of them, 59.2% were female. The most commonly encountered adverse drug reactions were nausea and vomiting (33.8%) and hair loss (29.3%). Most of the reactions were probable (61.1%) in causality, mild (66.2%) in severity, and not preventable (43.9%) in nature. Female sex (AOR = 1.054; 95% CI= (1.021-1.087); P = 0.001), number of chemotherapy treatments (AOR = 3.33; 95% CI= (1.301-8.52); P = 0.012), and elderly age (AOR = 3.065; 95% CI= (1.01-9.296); P = 0.048) were associated with occurrences of adverse drug reactions.

CONCLUSION: We can deduce from the data that adverse drug reactions are a significant concern for patients undergoing chemotherapy, with nearly two-thirds experiencing ADRs. The most common reactions are nausea and vomiting, which are mostly mild and probable. Age, gender, and the use of several chemotherapy drugs were associated with an increased risk of adverse drug reactions. Hence all concerned bodies should make an effort for early detection and take preventive measure of chemotherapy-related adverse drug reactions. Where feasible, use chemotherapy protocols with alower risk of ADRs. Evaluate dose adjustments for elderly patients. Implement protocols for risk assessment before initiating chemotherapy.

PMID:40378362 | DOI:10.1371/journal.pone.0321785

PLoS One. 2025 May 16;20(5):e0322378. doi: 10.1371/journal.pone.0322378. eCollection 2025.

ABSTRACT

OBJECTIVES: Brentuximab Vedotin (BV) is a novel antibody-drug conjugate (ADC) approved for the treatment of classical Hodgkin's lymphoma and systemic anaplastic large cell lymphoma. However, as a relatively new therapeutic agent, the long-term safety profile and adverse event (AE) profile of BV require further investigation. This study aimed to identify significant and unexpected AEs associated with BV using data from the FDA Adverse Event Reporting System (FAERS) and the Japanese Adverse Drug Event Report (JADER) databases.

METHODS: Data on BV-related AEs were extracted from the FAERS and JADER databases. Signal detection was performed using the reporting odds ratio (ROR) and 95% confidence intervals (95% CI). Risk signals were categorized according to system organ classes (SOCs) and preferred terms (PTs) as defined by the Medical Dictionary for Regulatory Activities (MedDRA) version 26.0. In addition, the onset times of BV-related AEs were analyzed.

RESULTS: Between 2004 and 2023, a total of 19,279 and 2,561 AEs related to BV were recorded in the FAERS and JADER databases, respectively. At the SOC level, prominent signals in the FAERS database included blood and lymphatic system disorders, benign, malignant, and unspecified neoplasms (including cysts and polyps), as well as congenital, familial, and genetic disorders. In the JADER database, the most notable signals involved benign, malignant, and unspecified neoplasms, blood and lymphatic system disorders, and nervous system disorders. At the PT level, the top five signals in the FAERS database were peripheral motor neuropathy, peripheral sensory neuropathy, pneumocystis jirovecii pneumonia, febrile bone marrow aplasia, and polyneuropathy. Unexpected AEs included febrile bone marrow aplasia and Guillain-Barré syndrome. In the JADER database, the top five signals included peripheral motor neuropathy, peripheral sensory neuropathy, bacterial gastroenteritis, febrile neutropenia and pneumonia, with unexpected AEs such as left ventricular dysfunction, cardiomegaly, retinal detachment, and marasmus. The median onset time of AEs was 22 days (interquartile range [IQR] 7-81 days) in FAERS and 27 days (IQR 7-73 days) in JADER.

CONCLUSION: The signal detection results from the FAERS and JADER databases highlight the importance of monitoring significant and unexpected AEs associated with BV, particularly in the early stages of treatment. These findings contribute to enhancing the post-marketing safety profile of BV and offer valuable insights for clinical risk management strategies.

PMID:40378127 | DOI:10.1371/journal.pone.0322378

Discov Oncol. 2025 May 16;16(1):786. doi: 10.1007/s12672-025-02502-6.

ABSTRACT

BACKGROUND: Drug-induced second tumors (DIST) refer to new primary cancers that develop during or after the treatment of an initial cancer due to the long-term effects of medications. As a severe long-term adverse event, DIST has gained widespread attention globally in recent years. With the increasing prevalence of cancer treatments and the prolonged survival of patients, drug-induced second tumors have become more prominent and pose a significant public health challenge. However, most existing studies have focused on individual drugs or small patient cohorts, lacking large-scale, real-world data evaluations. Particularly, the potential second-tumor risk of new drugs remains underexplored.

OBJECTIVE: This study aims to systematically assess the adverse event signals between drugs and second tumors using the U.S. FDA Adverse Event Reporting System (FAERS) database, employing disproportionality analysis (DPA) methods. It particularly focuses on uncovering drugs that have not clearly labeled second-tumor risks.

METHODS: Data from the FDA Adverse Event Reporting System (FAERS), covering reports from its inception to the third quarter of 2024, was retrieved. After data standardization, four disproportionality methods were used: Reporting Odds Ratio (ROR), Proportional Reporting Ratio (PRR), Bayesian Confidence Propagation Neural Network (BCPNN), and Multi-item Gamma Poisson Shrinker (MGPS). These methods assessed the correlation between azacitidine and adverse drug events (ADEs). Additionally, the Weibull Shape Parameter (WSP) was used to analyze the characteristic patterns of time-to-onset curves. Newly discovered signals were verified against FDA drug labels to confirm their novelty. The Weibull analysis was conducted to examine the temporal aspects of adverse event occurrences.

RESULTS: Since 2004, drug-induced tumor events have been increasing annually, with a total of 7597 drug-related tumor adverse events recorded. A total of 250 drugs were identified as having potential risk signals. High-incidence populations were primarily aged between 65 and 85 years, with a higher proportion of individuals with a body weight ≥ 90 kg. The most frequent occurrence was observed in patients with Chronic Myeloid Leukemia (13.36%). Among the top 5 drugs with the highest number of reported drug-induced second tumor adverse events, IMATINIB (906 reports), RUXOLITINIB (554 reports), PALBOCICLIB (552 reports), OCTREOTIDE (399 reports), and DOXORUBICIN (380 reports) were identified. Among these, PALBOCICLIB, OCTREOTIDE, and DOXORUBICIN are drugs for which the risk of drug-induced second tumors is not explicitly mentioned in their labels. A total of 76 drugs were identified through four disproportionality algorithms (ROR, PRR, MGPS, BCPNN), with a minimum time to drug-induced tumor occurrence of 5 years, exhibiting an early failure-type curve.

CONCLUSION: This study, based on large-scale real-world data, reveals the potential associations between drugs and second tumors, especially highlighting the risks of some new drugs. The findings provide valuable insights for drug safety monitoring and have significant public health implications. By uncovering previously unrecognized potential risks, this research lays the groundwork for further advancements in pharmacovigilance.

PMID:40377769 | DOI:10.1007/s12672-025-02502-6

Front Cardiovasc Med. 2025 May 1;12:1498700. doi: 10.3389/fcvm.2025.1498700. eCollection 2025.

ABSTRACT

OBJECTIVE: Utilizing the FDA Adverse Event Reporting System (FAERS) database, this study conducts signal detection for drugs associated with cardiac arrest (CA), aiming to optimize clinical decision-making and ensure safer drug usage.

METHODS: Adverse event reports related to CA from the first quarter of 2004 to the second quarter of 2024 were extracted from the FAERS database. Signal detection was conducted using the reporting odds ratio (ROR) and proportional reporting ratio (PRR) to identify drugs associated with an increased risk of CA.

RESULTS: A total of 66,431 reports were analyzed, comprising 34,508 males (51.9%) and 31,923 females (48.1%). The majority of cases (71.8%) were reported by healthcare professionals, with adults (≥18 years old) representing the predominant group. Clinical outcomes showed that 67.2% of cases resulted in death. Out of 82 drugs with over 100 CA-related reports, 43 displayed positive signals. The top five drugs identified by ROR were: carisoprodol [ROR (95% CI): 34.13 (29.62-39.32)], sugammadex [ROR (95% CI): 26.93 (22.56-32.16)], regadenoson [ROR (95% CI): 20.00 (17.69-22.60)], alprazolam [ROR (95% CI): 12.82 (12.19-13.48)], and propofol [ROR (95% CI): 11.93 (10.61-13.41)]. In the system drug signal detection, musculo-skeletal system drugs ranked highest [ROR (95% CI): 30.99 (27.74-34.62)], followed by alimentary tract and metabolism drugs [ROR (95% CI): 4.75 (4.59-4.92)], nervous system drugs [ROR (95% CI): 4.51 (4.4-4.61)], anti-infective drugs [ROR (95% CI): 4.13 (3.74-4.57)], cardiovascular drugs [ROR (95% CI): 3.89 (3.78-4.01)], and antineoplastic and immunomodulating agents [ROR (95% CI): 2.16 (2.13-2.2)].

CONCLUSION: This study identifies over 40 drugs potentially associated with an elevated risk of CA based on FAERS data. Healthcare professionals should be particularly vigilant when prescribing these drugs, especially to patients with a history of heart disease, and ensure rigorous monitoring of their cardiac health.

PMID:40376150 | PMC:PMC12078221 | DOI:10.3389/fcvm.2025.1498700

BMC Psychiatry. 2025 May 15;25(1):491. doi: 10.1186/s12888-025-06937-7.

ABSTRACT

BACKGROUND: Hypersensitivity to antipsychotic drugs is one of the supportive features of dementia with Lewy bodies, and side effects to drugs other than antipsychotics are also known to occur frequently. We experienced a case of dementia with Lewy bodies in which hallucinations and delusions repeatedly appeared and disappeared after administration and discontinuation of mirogabalin and pregabalin.

CASE PRESENTATION: The patient, a woman in her late 70s, developed hallucinations and delusional misidentification of places and persons immediately after receiving a prescription of mirogabalin (15 mg daily) for neuropathic pain. After discontinuation of mirogabalin, her hallucinatory delusions improved but remained. Mild dementia and mild parkinsonism were associated, cognitive fluctuations were evident, and dopamine-transporter scintigraphy showed bilateral striatal uptake reduction. Residual psychosis resolved with donepezil. Later, when the pain worsened, pregabalin (25 mg daily) was administered, and the psychosis recurred and resolved with discontinuation.

CONCLUSIONS: Although pregabalin-induced psychosis has been reported at higher doses (300-450 mg daily), it has not been reported at doses as low as those used in this patient. Gabapentinoids may cause psychosis in patients with dementia with Lewy bodies even at low doses, likely due to hypersensitivity to gabapentinoids in DLB.

PMID:40375230 | DOI:10.1186/s12888-025-06937-7

BMC Anesthesiol. 2025 May 15;25(1):247. doi: 10.1186/s12871-025-03109-8.

ABSTRACT

BACKGROUND: Children are at an increased risk of medication errors (MEs) during perioperative care compared to adult patients. This study aimed to critically look at medication errors and determine the frequency of adverse drug events and corrective measures taken for medication errors reported over 20 years in pediatric anesthetic care in the anesthesia department of a tertiary care teaching institution in a lower middle-income country (LMIC).

METHODS: Two investigators conducted a retrospective review of all critical incident forms received between January 2001 and December 2020 and identified medication errors related to patients aged 18 years or less. In the second phase of the audit, these medication errors were assessed in detail and adverse drug events were identified using a standardized protocol. We also analyzed the strategies that were employed to prevent such incidents in the future.

RESULTS: One hundred and ninety-six pediatric medication errors were identified. 40% of errors were reported in children between 13 and 72 months of age and 58% at induction. The majority of events took place during administration, preparation, and dispensing i.e., 45%, 41%, and 6% respectively. The adverse drug events occurred in 27 (1.2%) reports and life-threatening events in only one report.

CONCLUSION: 13% of the medication errors progressed to adverse drug events (ADE) and half of those were serious and life-threatening. Reinforcement of standard practice in departmental critical incident meetings, patient safety workshops and lessons to learn e-mails were some low-cost strategies to enhance medication safety during anesthesia.

PMID:40375141 | DOI:10.1186/s12871-025-03109-8

Front Immunol. 2025 Apr 30;16:1576283. doi: 10.3389/fimmu.2025.1576283. eCollection 2025.

ABSTRACT

Gliomas, particularly glioblastoma (GBM), are among the most aggressive and challenging brain tumors to treat. Although current therapies such as chemotherapy, radiotherapy, and targeted treatments have extended patient survival to some extent, their efficacy remains limited and is often accompanied by severe side effects. In recent years, exercise therapy has gained increasing attention as an adjunctive treatment in clinical and research settings. Exercise not only improves patients' physical function and cognitive abilities but may also enhance the efficacy of conventional drug treatments by modulating the immune system, suppressing inflammatory responses, and improving blood-brain barrier permeability. This review summarizes the potential mechanisms of exercise in glioma treatment, including enhancing immune surveillance through activation of natural killer (NK) cells and T cells, and increasing drug penetration by improving blood-brain barrier function. Additionally, studies suggest that exercise can synergize with chemotherapy and immunotherapy, improving treatment outcomes while reducing drug-related side effects. Although the application of exercise therapy in glioma patients is still in the exploratory phase, existing evidence indicates its significant clinical value as an adjunctive approach, with the potential to become a new standard in glioma treatment in the future.

PMID:40370453 | PMC:PMC12075166 | DOI:10.3389/fimmu.2025.1576283

Dermatol Ther (Heidelb). 2025 May 14. doi: 10.1007/s13555-025-01424-z. Online ahead of print.

ABSTRACT

INTRODUCTION: Bullous pemphigoid (BP) is a chronic autoimmune blistering disorder that imposes a significant health-related quality of life burden on the lives of patients; however, there are limited data on patient experiences.

METHODS: We conducted qualitative open-ended interviews of patients from the USA, Spain, and France, to understand BP symptoms and impacts, and develop a conceptual model. Adults with a confirmed BP diagnosis were included. Patients with pemphigus or drug-induced BP were excluded.

RESULTS: Thirty participants were recruited. The mean (standard deviation) age was 63.6 (16.0) years. Eleven signs and symptoms and 24 impacts were reported; six signs and symptoms, and 13 impacts affected ≥ 50% of participants with an average disturbance rating of ≥ 5 out of 10 (scale of 0 to 10 [0, not disturbing; 10, extremely disturbing]). All participants reported typical signs and symptoms of classic and/or mucosal BP. Overall, five of six salient symptoms and four of 13 salient impacts had an average disturbance rating of ≥ 7.5/10, indicating that BP is highly burdensome. Regarding corticosteroids, participants expressed a strong desire to avoid taking them again, due to the associated unwanted side effects.

CONCLUSION: The conceptual model presented here can be the basis for endpoint selection in studies of new therapies for BP.

PMID:40366568 | DOI:10.1007/s13555-025-01424-z

J Clin Med. 2025 May 1;14(9):3137. doi: 10.3390/jcm14093137.

ABSTRACT

Arterial hypertension is the most important modifiable cardiovascular risk factor and a major cause of cardiovascular mortality worldwide. In daily clinical practice, the hypertensive patient is often treated in a uniform way, thus ignoring the significant effects of sex on several aspects of hypertension, including its prevalence, pathophysiology, response to antihypertensive treatment, and outcomes. Along with the immune response and several cardiometabolic risk factors that frequently coexist, the substantial hormonal changes during a woman's life cycle are among the main pathophysiological mechanisms driving hypertension in women. Concurrently, women exhibit increased cardiovascular risk at lower blood pressure (BP) levels compared to age-matched men and present certain disparities in the incidence of cardiovascular events and subsequent hypertension-related cardiovascular prognosis. In addition, women respond differently to antihypertensive treatment, experience more drug-related side effects, and exhibit lower rates of BP control compared to men. Currently, international guidelines propose the same targets and the same therapeutic algorithms for the treatment of hypertension in both sexes without taking into account the sex differences that exist. In this review, we aim to describe certain particularities of arterial hypertension in the female sex, moving from pathophysiological aspects to clinical and therapeutical management.

PMID:40364167 | DOI:10.3390/jcm14093137

J Clin Med. 2025 Apr 27;14(9):3026. doi: 10.3390/jcm14093026.

ABSTRACT

Atopic dermatitis (AD) is a chronic inflammatory skin disease characterized by epidermal barrier dysfunction and immune dysregulation, with interleukin (IL)-4, IL-13, and IL-31 recognized as key mediators. Prurigo nodularis (PN) is another chronic inflammatory disorder driven by T helper type 2-mediated inflammation and neural dysregulation, leading to severe pruritus. Nemolizumab, a humanized monoclonal antibody targeting IL-31 receptor A, has been approved for use in the treatment of AD and PN. Clinical trials have demonstrated significant reductions in pruritus and cutaneous symptoms associated with its use. In clinical practice, acute eczema and edematous erythema frequently occur, occasionally necessitating the discontinuation of treatment. Despite these observations, no comprehensive review has examined nemolizumab-associated cutaneous adverse events. This review aimed to examine various cutaneous reactions associated with nemolizumab therapy, including psoriasiform eruptions, AD exacerbation, bullous pemphigoid, drug-induced eruptions, and fungal infections. Potential mechanisms underlying these reactions include T-cell activation due to drug sensitization, immune responses triggered by nemolizumab acting as a hapten, and a relative increase in IL-4 and IL-13 levels following IL-31 inhibition. However, the precise pathophysiological mechanism and risk factors remain unclear, and standardized clinical management guidelines are lacking. Further accumulation of clinical data and immunological research are essential for developing evidence-based strategies to manage these adverse events, ensuring treatment continuity and optimizing patient outcomes.

PMID:40364058 | DOI:10.3390/jcm14093026

Front Immunol. 2025 Apr 28;16:1527103. doi: 10.3389/fimmu.2025.1527103. eCollection 2025.

ABSTRACT

Immune checkpoint inhibitors (ICIs) have revolutionized cancer therapy by enhancing T-cell-mediated immune responses against tumors. However, their use can lead to immune-related adverse events (irAEs) impacting patient outcomes. This single-center, observational study investigates the relationship between immune-related adverse events (irAEs) and survival outcomes and, to our knowledge, is the first of this kind in Polish population. Data of the 151 patients treated with ICIs, with or without chemotherapy, at the Department of Clinical Oncology and Chemotherapy in the Independent Public Hospital No. 4 in Lublin were collected from electronic medical records. Statistical analyses were performed using the Kaplan-Meier estimator, log-rank test, and multivariable Cox proportional hazard model (p < 0.05). IrAEs were observed in 38% of the patients, with the most common being thyroid dysfunction (11.9%) and dermal toxicity (6.6%). The median OS for patients with irAEs was 18.7 months, compared to 13.6 months for those without irAEs, though the difference was not statistically significant (p = 0.284). Patients with moderate toxicity had the highest median OS (26 months), while those with severe toxicity had a median OS of 6.41 months. Late-onset irAEs were associated with improved OS and PFS. Pack-years of smoking significantly impacted both OS (HR = 1.01, p = 0.014) and PFS (HR = 1.01, p = 0.011). Despite results not reaching statistical significance, the findings emphasize the clinical relevance of irAEs in treatment optimization and warrant further research to better understand their role in patient outcomes.

PMID:40356892 | PMC:PMC12066656 | DOI:10.3389/fimmu.2025.1527103

Front Pharmacol. 2025 Apr 28;16:1563238. doi: 10.3389/fphar.2025.1563238. eCollection 2025.

ABSTRACT

BACKGROUND: Insulin glargine is a long-acting drug and the first synthetic insulin to mimic human metabolism. The safety of insulin glargine in the real world remains to be further investigated. This study aims to analyze insulin glargine-related adverse events (ADEs) to guide its safe clinical use.

METHODS: This study collected ADE reports from the FDA Adverse Event Reporting System (FAERS) between the first quarter of 2004 and the third quarter of 2024, where insulin glargine was identified as the primary suspect drug. Four disproportionate analytical methods were employed to analyze positive signals for drug-related ADEs, including the Reporting Odds Ratio (ROR), Proportional Reporting Ratio (PRR), Bayesian Confidence Propagation Neural Network (BCPNN), and Multi-item Gamma Poisson Shrinker (MGPS). The study also describes the time to onset of ADEs and uses the Weibull distribution to analyze the temporal trend of ADEs occurrence over time.

RESULTS: This study included 97,350 ADE reports, containing 228,258 ADEs, and identified 130 ADEs with positive signal. The study confirmed several known ADEs, such as hypoglycemia, injection site pain and acquired lipodystrophy. Additionally, several unexpected ADEs were identified, including pancreatic neoplasm, medullary thyroid cancer, and bone marrow tumor cell infiltration. 28.13% of ADEs occurred within the first month. The Weibull distribution indicated that the occurrence of ADEs decreased over time.

CONCLUSION: This study explored the real-world safety of insulin glargine and revealed several unexpected ADEs. These findings provide new insights into the safety profile of insulin glargine for clinicians."

PMID:40356973 | PMC:PMC12066629 | DOI:10.3389/fphar.2025.1563238

J Gastroenterol Hepatol. 2025 May 13. doi: 10.1111/jgh.17003. Online ahead of print.

ABSTRACT

PURPOSE: This study aimed to evaluate the prognostic effect of the cumulative dose (CD) of regorafenib on survival in patients with metastatic colorectal cancer (mCRC).

MATERIALS AND METHODS: This retrospective study utilized the Taipei Medical University Clinical Research Database for analysis. Patients aged ≥ 20 years with mCRC who were prescribed regorafenib between January 2014 and December 2021 were identified and then divided into low- and high-CD groups (≤ 4200 mg vs. > 4200 mg). Overall survival (OS), time-to-treatment discontinuation (TTD), and the incidence of five common adverse events were compared between groups. In addition, natural cubic splines were employed to examine the non-linear relationship between cumulative doses and survival in the multivariate Cox regression model.

RESULTS: A total of 259 patients were enrolled, with 130 in the low-CD group and 129 in the high-CD group; the median OS was 4.6 months and 9.8 months, respectively (p < 0.01). The median TTD was 51.5 days for the low-CD group and 72.0 days for the high-CD group (p < 0.01). No significant difference in drug-related adverse events was observed between groups. In the multivariate Cox analysis, a CD ≤ 4200 mg was a negative prognostic factor (hazard ratio 1.41 [95% confidence interval 1.08-1.84], p = 0.01). In addition, patients on a dose range between 4368 and 5376 mg exhibited minimal mortality risk.

CONCLUSION: The cumulative doses of regorafenib > 4200 mg were associated with improved survival. The suggested optimal dose range serves as a reference for dose modification in clinical practice.

PMID:40356543 | DOI:10.1111/jgh.17003

J Immunother Cancer. 2025 May 12;13(5):e011545. doi: 10.1136/jitc-2025-011545.

ABSTRACT

BACKGROUND: Immune checkpoint inhibitors (ICIs) have led to enduring responses in subsets of patients with cancer. However, these responses carry the risk of immune-related adverse events (irAEs), which can diminish the overall benefit of ICI treatment. While associations between irAE development and overall survival have been increasingly documented, there is a need for further understanding of these connections in large prospective real-world cohorts.

METHODS: The Resistance Drivers for Immuno-Oncology Patients Interrogated by Harmonized Molecular Datasets (RADIOHEAD) study, a pan-tumor, prospective cohort of 1,070 individuals undergoing standard of care first-line ICI treatment, aims to identify factors driving irAEs and clinical response. Clinical data and longitudinal blood samples were collected prospectively at multiple time points from 49 community-based oncology clinics across the USA. Structured, harmonized clinical data underwent unbiased statistical analysis to uncover predictors of real-world overall survival (rwOS) and risk factors for irAEs.

RESULTS: Across 1,070 participants' treatment courses, RADIOHEAD accumulated over 4,500 clinical data points. Patients experiencing any irAE (25.4%, n=272) exhibited significantly improved rwOS in the pan-tumor cohort (n=1,028, HR=0.41, 95% CI=(0.31, 0.55)). This association persisted when adjusting for age and metastatic disease in multivariate time-dependent Cox proportional hazard analysis, and was consistent across major tumor subtypes, including lung cancer and melanoma. Skin and endocrine irAEs of any grade were strongly associated with improved rwOS (Cox proportional hazard analysis, skin, p=2.03e-05; endocrine, p=0.0006). In this real-world cohort, the irAE rate appeared lower than those reported in clinical trials. Patients receiving corticosteroids prior to initiation of ICI treatment had significantly worse survival outcomes than non-users (HR 1.37, p=0.0054), with a stronger association with systemic steroid use (HR 1.75, p=0.0022). The risk of irAE was increased by exposure to combination immunotherapy relative to monotherapy (OR 4.17, p=2.8e-7), zoster vaccine (OR 2.4, p=5.2e-05), and decreased by prior chemotherapy (OR 1.69, p=0.0005).

CONCLUSION: The RADIOHEAD cohort is a well-powered, real-world cohort that clearly demonstrates the association between irAE development with improved response and baseline steroid use with worse response to ICI treatment after adjustment for survival bias.

PMID:40355283 | DOI:10.1136/jitc-2025-011545