Zhonghua Yi Xue Za Zhi. 2025 Jan 21;105(3):233-239. doi: 10.3760/cma.j.cn112137-20240725-01713.

ABSTRACT

Objective: To evaluate the efficacy of domestic and imported sugammadex for reversal of rocuronium-induced deep neuromuscular block (NMB) in adult patients. Methods: The clinical data of adult patients who scheduled for elective surgery with general anesthesia that required muscle relaxants in Peking University First Hospital from June 2023 to June 2024 were prospectively included. The patients were devided into domestic group and imported group according to random number table method. Anesthetized patients received rocuronium for intubation and muscle relaxation, and anesthesia was maintained with propofol, sevoflurane, and remifentanil. The effect of neuromuscular block was monitored. During deep muscle relaxation (with a single stimulation muscle twitch count of 1-2 after tetanic stimulation), domestic and imported sugammadex 4 mg/kg was given, respectively. The primary outcome was the recovery time from sugammadex injection to return of the train-of-four ratio (TOFr) to 0.9, with a non-inferiority margin of 1 minute (the range of non-inferiority boundary value is ±1 minute). The secondary outcome included the ratios of TOFr to 0.9 at different times and adverse effects. Results: A total of 70 patients were included, including 35 patients in the domestic group (13 males and 22 females), aged (46.9±12.7) years, and 35 patients in the imported group (13 males and 22 females), aged (45.7±11.5) years. There was no statistically significant difference in demographic characteristics, surgical time, anesthesia time, total rocuronium dose, and extubation time between two groups. All patients recovered to a TOFr of 0.9 within 5 minutes. Reversal time was 1.8 (1.3, 2.6) minutes in the domestic sugammadex group and 2.0 (1.7, 2.9) minutes in the imported sugammadex group respectively. The difference in reversal times between two groups was -0.40 minutes (95%CI:-0.75 to -0.02, P=0.039), which was within the range of non-inferiority threshold. Within 5 minutes of administration of antagonists, the incidence of bradycardia was 14% (5/35 and 5/35) in both domestic and imported groups. The incidence of skin allergy in patients transported to the post-anesthesia recovery room (PACU) was 3% (3/35) and 0 in both groups, respectively, with no statistical significance (all P>0.05). There were no serious drug-related adverse events in both groups. Conclusion: The effect of domestic sugammadex is not inferior to imported sugammadex in reversal of deep rocuronium-induced neuromuscular block in adult patients, and the incidence of postoperative adverse events is not increased.

PMID:39828581 | DOI:10.3760/cma.j.cn112137-20240725-01713

Dig Liver Dis. 2025 Jan 18:S1590-8658(25)00038-6. doi: 10.1016/j.dld.2025.01.037. Online ahead of print.

ABSTRACT

BACKGROUND: Immune-related sclerosing cholangitis (irSC) induced by immune checkpoint inhibitors (ICIs) is relatively rare, and its clinical and pathological features are not well known.

AIMS: We aimed to compare the clinical course and pathological findings of irSC with those of non-irSC liver injury.

METHODS: Clinical data were retrospectively collected from 2416 patients with advanced malignancies treated with ICIs between September 2014 and October 2023. The data of patients with severe ICI-induced liver injury who underwent liver biopsy were analyzed and compared between patients with irSC and non-irSC.

RESULTS: Ninety-three (3.8 %) patients had severe ICI-induced liver injury, and 38 underwent liver biopsy. Of these, five were diagnosed with irSC. The irSC group had a significantly longer time to onset of ICI-induced liver injury and a lower rate of improvement of liver injury than did the non-irSC group (irSC, 3/5; non-irSC, 32/33). Liver biopsies revealed more moderate-to-severe pathological cholangitis in the irSC group than in the non-irSC group (irSC, n = 5/5; non-irSC, n = 16/33). Other pathological findings were similar between the two groups.

CONCLUSION: Appropriate management of irSC requires an understanding of its characteristics of late onset and steroid resistance, and liver biopsy, in addition to imaging, may be useful for diagnosing irSC.

PMID:39828442 | DOI:10.1016/j.dld.2025.01.037

Hum Vaccin Immunother. 2025 Dec;21(1):2449714. doi: 10.1080/21645515.2025.2449714. Epub 2025 Jan 19.

ABSTRACT

To analyze the coverage rate of adult herpes zoster (HZ) vaccine and the incidence of Adverse event following immunization (AEFI) in Jiangsu province, China. The vaccination information of HZ vaccine in people aged 50 years and above in Jiangsu province in 2023 and the AEFI information of HZ vaccine from 2020 to 2023 were collected through the Jiangsu Province vaccination management information system and China AEFI information management system, and the vaccination rate and AEFI incidence of HZ vaccine were analyzed. The overall vaccination rate among individuals aged 50 years and above was merely 0.19%. About 20% of vaccinated individuals (12,821 people) received only the first dose, failing to complete the recommended two-dose regimen. A total of 43 and 217 cases of AEFIs following vaccination were reported after administration of the HZ vaccine during the periods of 2020-2021 and 2022-2023, respectively, resulting in reporting rates (RRs) of 240.7 and 201.2 per 100,000 doses, correspondingly. The majority of AEFIs following vaccination with HZ vaccines were common reactions, while rare reactions and coincidental events accounted for only 1.5% and 0.4% of cases, respectively. Over 55% of AEFIs occurred within 30 minutes post-vaccination , with fever, allergic eruptions, and drowsiness being the most reported systemic symptoms, and redness and induration being the main symptoms at the injection site. Despite the proven safety profile of the HZ vaccine, its coverage remains significantly low among individuals aged 50 years and above in Jiangsu Province, China as of 2023. The majority of AEFIs were mild and commonly observed. To enhance the comprehensiveness of post-marketing safety data, it is imperative to conduct further active surveillance studies.

PMID:39827897 | DOI:10.1080/21645515.2025.2449714

Sci Rep. 2025 Jan 17;15(1):2346. doi: 10.1038/s41598-025-86976-y.

ABSTRACT

Brodalumab, a humanized monoclonal antibody that targets the interleukin-17 receptor A, is primarily used to manage moderate-to-severe plaque psoriasis. Although it has demonstrated favorable efficacy and safety in clinical trials, the strict inclusion and exclusion criteria may not fully reflect its safety profile in real-world settings. As its use becomes more widespread in clinical practice, understanding its safety in real-world applications is crucial.This study employed disproportionality analysis to assess the safety of brodalumab by examining all adverse event reports that identified brodalumab as the primary suspected drug in the FDA Adverse Event Reporting System database since 2017. Techniques such as the Reporting Odds Ratio, Proportional Reporting Ratio, Multi-item Gamma Poisson Shrinker, and Bayesian Confidence Propagation Neural Network were utilized to analyze the adverse events associated with brodalumab. Additionally, the Weibull distribution was used to model the temporal risk of adverse events.The study identified several adverse reactions already listed on the drug's label that showed positive signals, including arthralgia, headache, myalgia, suicidal ideation, oropharyngeal pain, injection site mass, and infections. Additionally, we found potential adverse reactions not noted on the drug's label that exhibited positive signals, including depression, increased blood pressure, peripheral swelling, gait disturbance, inability to walk, stress, myocardial infarction, sepsis, uveitis, nephrolithiasis, and interstitial lung disease. Moreover, this analysis highlighted the critical need for vigilant monitoring of adverse events, especially during the first month following the initiation of treatment.This study provides initial insights into the real-world safety of brodalumab, confirming known adverse reactions and uncovering additional potential risks. The results deliver vital information that can assist clinicians in making informed decisions when prescribing brodalumab for psoriasis treatment.

PMID:39824966 | DOI:10.1038/s41598-025-86976-y

J Hepatol. 2025 Jan 15:S0168-8278(25)00002-9. doi: 10.1016/j.jhep.2024.12.045. Online ahead of print.

ABSTRACT

BACKGROUND & AIMS: Lanifibranor is a pan-PPAR agonist that improves glucose/lipid metabolism and reverses steatohepatitis and fibrosis in adults with MASH. We tested its effect on insulin resistance at the level of different target tissues in relationship to change in intrahepatic triglyceride (IHTG) content.

METHODS: This phase 2, single center, study randomized (1:1) 38 patients with T2D and MASLD to receive lanifibranor 800 mg or placebo for 24 weeks. The primary endpoint was the change in IHTG (1H-MRS). The main prespecified secondary endpoint was the change in hepatic, muscle and adipose tissue insulin sensitivity using the gold-standard euglycemic hyperinsulinemic clamp technique measuring glucose turnover. Other secondary endpoints included changes in cardiometabolic parameters (i.e., HbA1c, lipid profile, adiponectin).

RESULTS: Lanifibranor compared to placebo significantly lowered IHTG (full analysis set [FAS] -44% vs. -12%, respectively; least squares mean difference -31%, 95% CI -51 to -12%; in completers -50% vs. -16%; both p<0.01). More patients reached ≥30% IHTG reduction with lanifibranor compared to placebo (FAS 65% vs. 22%; completers 79% vs. 29%; both p<0.01) and steatosis resolution (FAS 25% vs. 0%; p<0.05). Lanifibranor significantly improved hepatic and peripheral insulin resistance (i.e., fasting endogenous [primarily hepatic] glucose production, hepatic IR, and insulin-stimulated muscle glucose disposal or Rd). Secondary metabolic endpoints also improved (fasting glucose, insulin, HOMA-IR, HbA1c; HDL-C), and adiponectin increased 2.4-fold (all p<0.001). Lanifibranor caused modest weight gain (+2.7%). Adverse events were mild (gastrointestinal side effects, hemoglobin decrease) and drug-related TEAE leading to study discontinuation were balanced between groups.

CONCLUSIONS: Lanifibranor significantly improves hepatic, muscle and adipose tissue insulin resistance. Lanifibranor treatment was safe and effective in reducing hepatic steatosis and cardiometabolic risk factors associated with metabolic dysfunction.

IMPACT AND IMPLICATIONS: No prior studies have evaluated the effect of lanifibranor on insulin sensitivity at the level of muscle, liver and adipose tissue and its relationship to changes in intrahepatic triglyceride (IHTG) content in insulin resistant subjects with MASLD and T2D. We observed a significant decrease in IHTG after 24 weeks of treatment (by ∼50%, p < 0.001 versus placebo) that was associated with a major improvement in hepatic and peripheral (Rd) insulin sensitivity, restoration of adipose tissue function with more than two-fold increase in plasma adiponectin concentration and improvement in cardiometabolic risk factors. This is the first in-depth study on how a pan-PPAR approach reverses steatosis and metabolic dysfunction in patients with T2D and MASLD. It has important clinical implications because it offers proof-of-concept that by targeting the key underlying metabolic defects in MASLD (i.e., insulin resistance, lipotoxicity and hyperglycemia) one can restore cardiometabolic health and offers a compelling rationale for treating with lanifibranor individuals with MASLD, either alone or in combination with weight loss and other treatment strategies.

GOV IDENTIFIER: NCT03459079.

PMID:39824443 | DOI:10.1016/j.jhep.2024.12.045

Drug Dev Res. 2025 Feb;86(1):e70045. doi: 10.1002/ddr.70045.

ABSTRACT

Famotidine is an H2 receptor antagonist and is currently used on a large scale in gastroenterology. However, Famotidine may also cause severe toxicity to organ systems, including the blood system, digestive system, and urinary system. The objective of this study was to scientifically and systematically investigate the adverse events (AEs) of Famotidine in the real world through the FDA Adverse Event Reporting System (FAERS) database. A disproportionality analysis was used to quantify the signals of AEs associated with Famotidine in FAERS data from the first quarter of 2004 to the first quarter of 2023. The clinical features, onset time, oral and intravenous administration and severe consequences of Famotidine induced AEs were further analyzed. Among the four tests, we found several AEs that were not mentioned in the drug label. For example, abdominal pain upper, abdominal discomfort, dyspepsia, liver disorder, gastrooesophageal reflux disease, and rhabdomyolysis. These AEs are consistent with the drug instructions. Interestingly, we found several unreported AEs, such as: cerebral infarction, hypocalcaemia, hallucination, visual, hypomagnesaemia, hypoparathyroidism, diabetes insipidus, vulvovaginal candidiasis, retro-orbital neoplasm, neuroblastoma recurrent, and malignant cranial nerve neoplasm. Most of our findings are consistent with clinical observations and drug labels, and we also found possible new and unexpected AEs signals, which suggest the need for prospective clinical studies to confirm these results and explain their relationships. Our findings provide valuable evidence for further safety studies.

PMID:39821365 | DOI:10.1002/ddr.70045

Drugs. 2025 Jan 17. doi: 10.1007/s40265-024-02133-1. Online ahead of print.

ABSTRACT

Liposomal irinotecan (Onivyde®), also known as liposomal pegylated irinotecan, has been developed with the intent of maximising anti-tumour efficacy and minimising drug-related toxicities compared with conventional formulations of this topoisomerase 1 inhibitor. In combination with fluorouracil, leucovorin and oxaliplatin (NALIRIFOX), liposomal irinotecan is approved in the USA and the EU for first-line therapy of eligible patients with metastatic pancreatic adenocarcinoma. In a phase III clinical trial, NALIRIFOX significantly improved overall survival (OS) and progression free survival (PFS) compared with gemcitabine plus nanoparticle albumin bound paclitaxel (nab-paclitaxel) as first-line treatment of patients with metastatic pancreatic ductal adenocarcinoma (mPDAC). The safety profile of NALIRIFOX was generally manageable, with diarrhoea, hypokalaemia and neutropenia being the most common grade ≥ 3 treatment-emergent adverse events. Although further analyses will help position the liposomal irinotecan-containing regimen NALIRIFOX in first-line treatment of metastatic pancreatic adenocarcinoma, current evidence indicates that it is a useful addition to treatment options in this patient population.

PMID:39820839 | DOI:10.1007/s40265-024-02133-1

Immunopharmacol Immunotoxicol. 2025 Jan 16:1-13. doi: 10.1080/08923973.2025.2454030. Online ahead of print.

ABSTRACT

BACKGROUND: The incidence of hepatic immune-related adverse events has increased with the wide use of immune checkpoint inhibitors, some immune-mediated hepatotoxicity cases are severe and lack of clinical recommendations.

OBJECTIVE: This study aimed to evaluate the efficacy of artificial liver support systems (ALSS) in the treatment of immune-mediated hepatotoxicity.

METHODS: This retrospective case series included six patients with grade 4 hepatotoxicity with high bilirubin induced by immune checkpoint inhibitors treated between January 1, 2019, to December 31, 2021. All patients received ALSS treatment.

RESULTS: After treatment and recovery, four of the six patients experienced improvement in hepatotoxicity, with total bilirubin levels reduced to ≤ grade 2, and two patients achieved complete recovery (total bilirubin grade = 0).

CONCLUSION: ALSS serve as a therapeutic option for severe immune-mediated hepatotoxicity.

PMID:39819181 | DOI:10.1080/08923973.2025.2454030

Am J Hosp Palliat Care. 2025 Jan 17:10499091251313757. doi: 10.1177/10499091251313757. Online ahead of print.

ABSTRACT

BACKGROUND: Nausea and vomiting significantly impact the quality of life in palliative care. Due to various underlying causes, treatment approaches vary. However, scientific evidence on pharmacotherapeutic management is limited, complicating treatment decisions. Objective is to assess the current antiemetic treatment approach in palliative care in Germany.

METHODS: A retrospective observational study (15 months) was conducted, evaluating clinical records of adult patients admitted to palliative care in a German hospital. Symptom burden (Integrated Palliative care Outcome Scale (IPOS®)), suspected aetiology, antiemetics, treatment quality and drug-related problems (DRPs) were evaluated.

RESULTS: We included 330 patients (median age 71 years, 50.9% female), of which 172 (52%) experienced nausea/vomiting in 230 treatment episodes. Symptoms were more prevalent in cancer-patients (P = 0.002) and women (P = 0.002). Main aetiologies were intestinal obstruction (59/230, 25.7%), hypomotility (31/230, 16.1%), and raised intracranial pressure (23/230, 10.0%). Nearly 70% experienced a reduction of symptom burden within the first 3 days, with faster symptom relief and shorter episodes in cancer patients compared to non-cancer patients (median length 3d vs 2d). DRPs were documented in 213/230 episodes (92.6%), indicating high interaction potential of antiemetics (87.4%). Manifest DRPs affected patients due to ineffective treatment (29.0%) or side effects (6.5%).

CONCLUSIONS: One-third experienced inadequate symptom control with the current treatment, underscoring the complexity of managing nausea/vomiting in palliative care and the need for a systematic approach. This study emphasizes the importance of evidence-based guidelines and further research into underutilized antiemetics, along with improved medical education in an interdisciplinary team to enhance treatment quality.

PMID:39819071 | DOI:10.1177/10499091251313757

J Affect Disord. 2025 Jan 14:S0165-0327(25)00067-9. doi: 10.1016/j.jad.2025.01.054. Online ahead of print.

ABSTRACT

BACKGROUND AND OBJECTIVE: To determine whether there is disproportionate reporting of hepatobiliary disorders in the United States (US) FDA Adverse Event Reporting System (FAERS) for individuals prescribed ketamine or esketamine.

DESIGN: We identified Medical Dictionary for Regulatory Activities (MedDRA) terms in the FAERS related to hepatobiliary disorders.

MAIN MEASURES: Formulations of ketamine and esketamine were evaluated for the proportionality of reporting for each hepatobiliary disorder parameter using the reporting odds ratio (ROR). We also estimated the lower limits of 95 % confidence intervals of information components (IC025) to determine whether the association was significant. Acetaminophen was used as the positive reference agent and lithium as the neutral reference agent.

KEY RESULTS: We observed disproportionately lower reporting of hepatitis, liver disorder, liver injury, drug-induced liver injury, hepatic failure, and acute hepatic failure for ketamine compared to acetaminophen. Additionally, we observed disproportionately higher reporting of hepatic function abnormalities and hepatic cytolysis for ketamine compared to acetaminophen. For esketamine, we did not find disproportionate reporting of any hepatobiliary toxicity relative to acetaminophen. However, for ketamine, there was disproportionate lower reporting of hepatic function abnormalities, liver disorder and hepatic cirrhosis. In contrast, for esketamine, there was disproportionately higher reporting of hepatic failure.

CONCLUSIONS: Although causality has not been established, the data support recommendations for periodic monitoring of liver function tests, as well as clinical surveillance for stigmata of hepatobiliary disease in individuals receiving chronic exposure to ketamine and esketamine.

PMID:39818335 | DOI:10.1016/j.jad.2025.01.054

BMC Bioinformatics. 2025 Jan 15;26(1):16. doi: 10.1186/s12859-024-06028-6.

ABSTRACT

In recent years, combined drug screening has played a very important role in modern drug discovery. Generally, synergistic drug combinations are crucial in treatment for many diseases. However, the toxic side effects of drug combinations are probably increased with the increase of drugs numbers, so the accurate prediction of toxic side effects of drug combinations is equally important. In this paper, we built a Metapath-based Aggregated Embedding Model on Single Drug-Side Effect Heterogeneous Information Network (MAEM-SSHIN), which extracts feature from a heterogeneous information network of single drug side effects, and a Graph Convolutional Network on Combinatorial drugs and Side effect Heterogeneous Information Network (GCN-CSHIN), which transforms the complex task of predicting multiple side effects between drug pairs into the more manageable prediction of relationships between combinatorial drugs and individual side effects. MAEM-SSHIN and GCN-CSHIN provided a united novel framework for predicting potential side effects in combinatorial drug therapies. This integration enhances prediction accuracy, efficiency, and scalability. Our experimental results demonstrate that this combined framework outperforms existing methodologies in predicting side effects, and marks a significant advancement in pharmaceutical research.

PMID:39815175 | DOI:10.1186/s12859-024-06028-6

JMIR Res Protoc. 2025 Jan 15;14:e60084. doi: 10.2196/60084.

ABSTRACT

BACKGROUND: Adverse medicine events (AMEs) are unintended effects that occur following administration of medicines. Up to 70% of AMEs are not reported to, and hence remain undetected by, health care professionals and only 6% of AMEs are reported to regulators. Increased reporting by consumers, health care professionals, and pharmaceutical companies to medicine regulatory authorities is needed to increase the safety of medicines.

OBJECTIVE: We describe a project that aims to co-design a digital reporting platform to improve detection and management of AMEs by consumers and health care professionals and improve reporting to regulators.

METHODS: The project will be conducted in 3 phases and uses a co-design methodology that prioritizes equity in designing with stakeholders. Our project is guided by the Consolidated Framework for Implementation Research. In phase 1, we will engage with 3 stakeholder groups-consumers, health care professionals, and regulators-to define digital platform development standards. We will conduct a series of individual interviews, focus group discussions, and co-design workshops with the stakeholder groups. In phase 2, we will work with a software developer and user interaction design experts to prototype, test, and develop the digital reporting platform based on findings from phase 1. In phase 3, we will implement and trial the digital reporting platform in South Australia through general practices and pharmacies. Consumers who have recently started using medicines new to them will be recruited to use the digital reporting platform to report any apparent, suspected, or possible AMEs since starting the new medicine. Process and outcome evaluations will be conducted to assess the implementation process and to determine whether the new platform has increased AME detection and reporting.

RESULTS: This project, initiated in 2023, will run until 2026. Phase 1 will result in persona profiles and user journey maps that define the standards for the user-friendly platform and interactive data visualization tool or dashboard that will be developed and further improved in phase 2. Finally, phase 3 will provide insights of the implemented platform regarding its impact on AME detection, management, and reporting. Findings will be published progressively as we complete the different phases of the project.

CONCLUSIONS: This project adopts a co-design methodology to develop a new digital reporting platform for AME detection and reporting, considering the perspectives and lived experience of stakeholders and addressing their requirements throughout the entire process. The overarching goal of the project is to leverage the potential of both consumers and technology to address the existing challenges of underdetection and underreporting of AMEs to health care professionals and regulators. The project potentially will improve individual patient safety and generate new data for regulatory purposes related to medicine safety and effectiveness.

INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/60084.

PMID:39813668 | DOI:10.2196/60084

Dermatol Ther (Heidelb). 2025 Jan 15. doi: 10.1007/s13555-024-01334-6. Online ahead of print.

ABSTRACT

INTRODUCTION: Results from randomized controlled trials of upadacitinib, a Janus kinase (JAK) inhibitor, have led to its approval for the treatment of moderate-to-severe atopic dermatitis (AD) in patients aged ≥ 12 years. The aim of this study was to report the effectiveness and safety of upadacitinib in real-world settings over a period of 96 weeks.

METHODS: This retrospective study included all patients treated with upadacitinib at our centre between April 2022 and September 2024. Clinical and patient-reported outcomes were recorded and assessed at each follow-up visit and included the eczema area severity index (EASI), investigator global assessment (IGA), scoring atopic dermatitis (SCORAD), dermatology life quality index (DLQI) and the worst pruritus numerical scale score (WP-NRS). All drug-related adverse events (AEs) were documented.

RESULTS: In total, 36 patients (44.4% female) were retrospectively included. After 4 weeks of treatment, the mean EASI was reduced from 29.97 to 3.72 with 83.3/52.8/19.4% achieving EASI75/90/100 respectively. Similar reductions were observed in the DLQI, which was reduced from 20.78 to 2.92, and in the WP-NRS, from 7.78 to 1.31. Further improvements were observed at week 16, with a mean EASI of 0.75 and 96.4% of the patients achieving EASI75 and EASI90. At week 48 of treatment, EASI75/90/100 were achieved by 100/93.8/81.3% along with a mean DLQI and pruritus NRS of 0.81. All nine patients that reached the 72- and 96-week timepoints had clear skin with no pruritus. Six (16.7%) patients experienced AEs with four of them discontinuing medication; no patient discontinued because of upadacitinib inefficacy.

CONCLUSION: This long-term real-world study of patients with moderate-to-severe AD receiving upadacitinib demonstrated that treatment success (EASI75/90/100) can be achieved in a high proportion of patients by week 16 and can be maintained for up to 96 weeks along with substantial improvements in pruritus and quality of life.

PMID:39812942 | DOI:10.1007/s13555-024-01334-6

Drug Metab Rev. 2025 Jan 15:1-34. doi: 10.1080/03602532.2025.2453521. Online ahead of print.

ABSTRACT

Idiosyncratic drug reactions (IDRs) pose severe threats to patient health. Unlike conventionally dose-dependent side effects, they are unpredictable and frequently manifest as life-threatening conditions, such as severe cutaneous adverse reactions (SCARs) and drug-induced liver injury (DILI). Some HLA alleles, such as HLA-B*57:01, HLA-B*15:02, and HLA-B*58:01, are known risk factors for adverse reactions induced by multiple drugs. However, the structural basis underlying most HLA-associated adverse events remains poorly understood. This review summarizes the application of molecular docking to reveal the mechanisms of IDR-related HLA associations, covering studies using this technique to examine drug-HLA binding pockets and identify key binding residues. We provide a comprehensive overview of risk HLA alleles associated with IDRs, followed by a discussion of the utility and limitations of commonly used molecular docking tools in simulating complex molecular interactions within the HLA binding pocket.Through examples, including the binding of abacavir to HLA-B*57:01, carbamazepine to HLA-B*15:02, and allopurinol to HLA-B*58:01, we demonstrate how docking analyses can provide insights into the drug and HLA allele-specificity of adverse events. Furthermore, the use of molecular docking to screen drugs with unknown IDR liability is examined, targeting either multiple HLA variants or a single specific variant. Despite multiple challenges, molecular docking presents a promising toolkit for investigating drug-HLA interactions and understanding IDR mechanisms, with significant implications for preemptive HLA typing and safer drug development.

PMID:39811883 | DOI:10.1080/03602532.2025.2453521

Aging Clin Exp Res. 2025 Jan 14;37(1):23. doi: 10.1007/s40520-024-02921-5.

ABSTRACT

OBJECTIVE: This study aims to analyze adverse drug events (ADE) related to romosozumab from the second quarter of 2019 to the third quarter of 2023 from FAERS database.

METHODS: The ADE data related to romosozumab from 2019 Q2 to 2023 Q3 were collected. After data normalization, four signal strength quantification algorithms were used: ROR (Reporting Odds Ratios), PRR (Proportional Reporting Ratios), BCPNN (Bayesian Confidence Propagation Neural Network), and EBGM (Empirical Bayesian Geometric Mean).

RESULTS: Screening for romosozumab-related AEs (adverse events) included 23 system organ categories (SOCs). PT (preferred terms) levels were screened for adverse drug reaction (ADR) signals. A total of 7055 reports with romosozumab as the primary suspect (PS) and 14,041 PTs induced by romosozumab as PS were identified. Common significant signals of general disorders and administration site conditions, musculoskeletal and connective tissue disorders have emerged. Specifically, unexpected AEs such as gastrointestinal disorder, respiratory, thoracic and mediastinal disorders also occur. Notably, fracture (n = 503, ROR = 107.8, PRR = 103.83, IC = 6.6, EBGM = 97.02) and bone density abnormal (n = 429, ROR = 343.65, PRR = 332.77, IC = 8.08, EBGM = 271.34) exhibited relatively high occurrence rates and signal strengths.

CONCLUSION: Our study identifies potential new AE signals and provides broader data support for the safety of romosozumab. In clinical application, doctors are provided with a warning to closely monitor adverse reactions to support their rational use in diseases such as osteoporosis.

PMID:39808360 | DOI:10.1007/s40520-024-02921-5

J Acquir Immune Defic Syndr. 2024 Dec 1;97(4):379-386. doi: 10.1097/QAI.0000000000003506.

ABSTRACT

BACKGROUND: On demand, topical PrEP is desired by those preferring episodic, nonsystemic PrEP. PC-1005 gel (MIV-150, zinc, and carrageenan) exhibits in vitro antiviral HIV-1, human papillomavirus (HPV), and herpes simplex virus type 2 (HSV-2) activity, attractive for a multipurpose prevention technology candidate. We evaluated the safety, pharmacokinetics, and antiviral effect of rectally applied PC-1005.

METHODS: HIV-uninfected adults received a series of 3 rectal PC-1005 doses-4, 16, and 32 mL separated by 2-week washout periods. Following each dose, plasma, rectal fluid and tissue, and vaginal fluid were collected over 48 hours.

RESULTS: Thirteen adults enrolled; 12 completed all 3 doses. All 13 adverse events reported were grade 1 or 2; 5 were judged study drug related. Plasma MIV-150 peaked 1-2 h after dosing with a median peak concentrations range of 0.07-0.23 ng/mL and median half-life range of 4.9-7.4 hours across dose volumes; median concentrations were below assay quantitation limits (BLQ) 24 hours after dosing. Rectal tissue MIV-150 peaked 0.5-1 hours after dosing at 1.4 ng/g (ng/mL) (0.8, 1.9), 46.0 (30.7, 831.0), and 79.7 (11.9, 116.0), respectively, after each dose volume; median tissue concentrations were BLQ beyond 5 hours for all doses. All vaginal fluid samples were BLQ. Ex vivo antiviral assays showed 5 hours of antiviral HPV and HSV effects but no anti-HIV activity.

CONCLUSIONS: MIV-150 rectal tissue concentrations were below the 100 ng/g target concentration and transient. Ex vivo assays demonstrated antiviral HSV and HPV effects but not against HIV. PC-1005 requires a more potent antiviral and longer-lasting formulation for further consideration as a multipurpose prevention technology candidate.

CLINICAL TRIALS: NCT03408899.

PMID:39808074 | DOI:10.1097/QAI.0000000000003506

Pharmacoepidemiol Drug Saf. 2025 Jan;34(1):e70088. doi: 10.1002/pds.70088.

ABSTRACT

Drug-drug interactions (DDIs) represent a significant concern for clinical care and public health, but the health consequences of many DDIs remain largely underexplored. This knowledge gap underscores the critical need for pharmacoepidemiologic research to evaluate real-world health outcomes of DDIs. In this review, we summarize the definitions commonly used in pharmacoepidemiologic DDI studies, discuss common sources of bias, and illustrate through examples how these biases can be mitigated.

PMID:39805810 | DOI:10.1002/pds.70088

Pharmacoepidemiol Drug Saf. 2025 Jan;34(1):e70097. doi: 10.1002/pds.70097.

ABSTRACT

PURPOSE: This study aimed to obtain a better understanding of the characteristics of the risk management plans (RMP) and the background regulatory policies governing them, in the European Union (EU) and Japan. This was done by descriptively comparing the safety concerns (SCs) listed in the RMP and examining their relationships with product labeling.

METHODS: Information regarding SCs was collected from the published RMP of both the EU and Japan for the targeted products-all of which were commonly approved in both regions. The concordance rate of the SCs for each product between the EU- and Japan-RMP was calculated. The warning information for each product was collected from the product labeling, summary of product characteristics for the EU, and package insert for Japan, and compared with the SCs listed in the corresponding RMP.

RESULTS: A total of 259 products that were approved for sale in both the EU and Japan (1998-2023), for which RMP were available in both regions, were analyzed. While 51.0% of the SCs labeled as important identified risks (IIRs) in the EU-RMP were concordant with those in the Japan-RMP, 20.4% of the SCs listed as IIRs in the Japan-RMP were concordant with those in the EU-RMP. The concordance rate between the SCs identified as IIRs and the warning information was 18.6% for the EU-RMP and 88.4% for the Japan-RMP.

CONCLUSIONS: The low SC concordance rate between the EU- and Japan-RMP indicates a different approach to selecting RMP SCs by the two regulatory authorities.

PMID:39805803 | DOI:10.1002/pds.70097

Arch Dermatol Res. 2025 Jan 13;317(1):231. doi: 10.1007/s00403-024-03763-x.

ABSTRACT

Pityriasis rosea (PR) is an acute exanthematous disease with an uncertain physiopathology, increasingly recognized as potentially drug induced. This study aims to investigate medication triggers associated with PR by analyzing cases reported in the FDA Adverse Event Reporting System (FAERS) database. A retrospective review of 343 PR cases reported in the FAERS database from January 1, 1998, to March 31, 2024, was conducted. Reporting odds ratios (ROR) were calculated to assess associations between PR and specific drug classes, including tumor necrosis factor (TNF) inhibitors and angiotensin-converting enzyme (ACE) inhibitors. Logistic regression analysis evaluated the influence of factors such as sex, age group, and seriousness of outcomes on the occurrence of PR. Females represented 56.3% of cases and the 18-64 age group comprised 55.4% of cases. TNF inhibitors were significantly associated with PR (ROR = 4.1881 [3.1970-5.4865], P < 0.0001), particularly infliximab (ROR = 6.5284 [3.9523-10.7837], P < 0.0001), etanercept (ROR = 3.4921 [2.2873-5.3315], P < 0.0001), and adalimumab (ROR = 3.086 [2.0213-4.7115], P < 0.0001). ACE inhibitors were also associated with PR (ROR = 9.9808 [6.0423-16.4864], P < 0.0001), with higher odds in older patients (OR 14.08 [4.2-47.2], P < 0.0001) and those reporting serious outcomes (OR 9.53 [1.24-72.99], P = 0.03). Based on the FAERS, there has been a consistent rise in PR cases, with TNF inhibitors and ACE inhibitors being associated medication classes tied to PR. Given the limited literature on drug-related triggers and patient demographics, we aimed to highlight the characteristics of PR cases that could enhance awareness and inform better clinical outcomes for affected patients.

PMID:39804489 | DOI:10.1007/s00403-024-03763-x

Egypt J Immunol. 2025 Jan;32(1):27-41.

ABSTRACT

Cryptococcal meningitis is an alarming fungal infection that usually affects the meninges surrounding the brain and spinal cord. The causative organism is Cryptococcus neoformans. Although this infection can occur in normal individuals, it is more often seen in patients with human immunodeficiency virus/acquired immunodeficiency syndrome. Amphotericin B is an antifungal medication often used to treat severe fungal infections. It belongs to the class of polyene antifungal drugs, and it acts by binding to the cell membrane of the fungus. This causes some essential cellular components to leak out and ultimately the fungus dies. However, the administration of Amphotericin B is associated with toxicity. Therefore, lipid formulations are preferred to decrease the toxicity and increase the therapeutic index of the drug. It is widely used since it has a longer tissue half-life, the drug induced toxic effects are lower and it can penetrate the brain tissue efficaciously. This review collects and analyzes several research studies and literature reviews found in the electronic databases. The inclusion criteria prioritize studies focusing on the efficacy and drawbacks of using liposomal Amphotericin B as a treatment for fungal meningitis. In conclusion, liposomal Amphotericin B showed more effective treatment compared to other available antifungal drugs. Patients treated with a single dose of liposomal Amphotericin B coupled with fluconazole and flucytosine exhibited fewer adverse events and the mortality rate was also lower as compared to the control group.

PMID:39803853