Safety of immune checkpoint inhibitors in patients aged over 80 years: a retrospective cohort study.

BACKGROUND: Immuno-oncology (IO) drugs are essential for treating various cancer types; however, safety concerns persist in older patients. Although the incidence of immune-related adverse events (irAEs) is similar among age groups, higher rates of hospitalization or discontinuation of IO therapy have been reported in older patients. Limited research exists on IO drug safety and risk factors in older adults. Our investigation aimed to assess the incidence of irAEs and identify the potential risk factors associated with their development. METHODS: This retrospective analysis reviewed the clinical data extracted from the medical records of patients aged > 80 years who underwent IO treatment at our institution. Univariate and multivariate analyses were performed to assess the incidence of irAEs. RESULTS: Our study included 181 patients (median age: 82 years, range: 80-94), mostly men (73%), with a performance status of 0-1 in 87% of the cases; 64% received IO monotherapy. irAEs occurred in 35% of patients, contributing to IO therapy discontinuation in 19%. Our analysis highlighted increased body mass index, eosinophil counts, and albumin levels in patients with irAEs. Eosinophil count emerged as a significant risk factor for any grade irAEs, particularly Grade 3 or higher, with a cutoff of 118 (/µL). The group with eosinophil counts > 118 had a higher frequency of irAEs, and Grade 3 or higher events than the group with counts ≤ 118. CONCLUSION: IO therapy is a safe treatment option for patients > 80 years old. Furthermore, patients with elevated eosinophil counts at treatment initiation should be cautiously managed.

Adverse events associated with immune checkpoint inhibitors in non-small cell lung cancer: a safety analysis of clinical trials and FDA pharmacovigilance system.

Objectives: Immune checkpoint inhibitors (ICIs) have revolutionized the treatment of non-small cell lung cancer (NSCLC). However, the application of ICIs can also cause treatment-related adverse events (trAEs) and immune-related adverse events (irAEs). This study was to evaluate both the irAEs and trAEs of different ICI strategies for NSCLC based on randomized clinical trials (RCTs). The study also examined real-world pharmacovigilance data from the Food and Drug Administration Adverse Event Reporting System (FAERS) regarding claimed ICI-associated AEs in clinical practice. Methods: Based on Pubmed, Embase, Medline, and the Cochrane CENTRAL, we retrieved RCTs comparing ICIs with chemotherapy drugs or with different ICI regimens for the treatment of NSCLC up to October 20, 2023. Bayesian network meta-analysis (NMA) was performed using odds ratios (ORs) with 95% credible intervals (95%CrI). Separately, a retrospective pharmacovigilance study was performed based on FAERS database, extracting ICI-associated AEs in NSCLC patients between the first quarter (Q1) of 2004 and Q4 of 2023. The proportional reports reporting odds ratio was calculated to analyze the disproportionality. Results: The NMA included 51 RCTs that involved a total of 26,958 patients with NSCLC. Based on the lowest risk of any trAEs, cemiplimab, tislelizumab, and durvalumab were ranked as the best. Among the agents associated with the lowest risk of grades 3-5 trAEs, tislelizumab, avelumab, and nivolumab were most likely to rank highest. As far as any or grades 3-5 irAEs are concerned, atezolizumab plus bevacizumab plus chemotherapy is considered the most safety option. However, it is associated with a high risk of grades 3-5 trAEs. As a result of FAERS pharmacovigilance data analysis, 9,420 AEs cases have been identified in 7,339 NSCLC patients treated with ICIs, and ICIs were related to statistically significant positive signal with 311 preferred terms (PTs), and comprehensively investigated and identified those AEs highly associated with ICIs. In total, 152 significant signals were associated with Nivolumab, with malignant neoplasm progression, death, and hypothyroidism being the most frequent PTs. Conclusion: These findings revealed that ICIs differed in their safety profile. ICI treatment strategies can be improved and preventive methods can be developed for NSCLC patients based on our results.

Mortality and years of life lost related to adverse drug events in Brazil.

OBJECTIVE: To assess regional and national mortality and years of life lost (YLL) related to adverse drug events in Brazil. METHODS: This is an ecological study in which death records from 2009 to 2018 from the Mortality Information System were analyzed. Codes from the International Classification of Diseases 10th revision (ICD-10) that indicated drugs as the cause of death were identified. The number of deaths and the YLL due to adverse drug events were obtained. Crude, age- and gender-specific, and age-adjusted mortality rates and YLL rates per 100,000 inhabitants were formed by year, age group, gender, and Brazilian Federative Unit. Rate ratios were calculated by comparing rates from 2009 to 2018. A joinpoint regression model was applied for temporal analysis. RESULTS: For the selected ICD-10 codes, a total of 95,231 deaths and 2,843,413 YLL were recorded. Mortality rates from adverse drug events increased by a mean of 2.5% per year, and YLL rates increased by 3.7%. Increases in rates were observed in almost all age groups for both genders. Variations in rates were found between Federative Units, with the highest age-adjusted mortality and YLL rates occurring in the Distrito Federal. CONCLUSIONS: The numbers and rates of deaths and YLL increased during the study period, and variations in rates of deaths and YLL were observed between Brazilian Federative Units. Information on multiple causes of death from death certificates can be useful for quantifying adverse drug events and analyzing them geographically, by age and by gender.

Determination of drug-related problems in the hematology service: a prospective interventional study.

BACKGROUND: Patients with hematological malignancies often require multidrug therapy using a variety of antineoplastic agents and supportive care medications. This increases the risk of drug-related problems (DRPs). Determining DRPs in patients hospitalized in hematology services is important for patients to achieve their drug treatment goals and prevent adverse effects. This study aims to identify DRPs by the clinical pharmacist in the multidisciplinary team in patients hospitalized in the hematology service of a university hospital in Turkey. METHODS: This study was conducted prospectively between December 2022 and May 2023 in the hematology service of Suleyman Demirel University Research and Application Hospital in Isparta, Turkey. DRPs were determined using the Pharmaceutical Care Network Europe (PCNE) 9.1 Turkish version. RESULTS: This study included 140 patients. Older age, longer hospital stay, presence of acute lymphoblastic leukemia, presence of comorbidities, higher number of medications used, and polypharmacy rate were statistically significantly higher in the DRP group than in the non-DRP group (p < 0.05). According to multivariate logistic regression analysis, the probability of DRP in patients with polypharmacy was statistically significant 7.921 times (95% CI: 3.033-20.689) higher than in patients without polypharmacy (p < 0.001).Every 5-day increase in the length of hospital stay increased the likelihood of DRP at a statistically significant level (OR = 1.476, 95% CI: 1.125-1.938 p = 0.005). In this study, at least one DRP was detected in 69 (49.3%) patients and the total number of DRPs was 152. Possible or actual adverse drug events (96.7%) were the most common DRPs. The most important cause of DRPs was drug choice (94.7%), and the highest frequency within its subcategories was the combination of inappropriate drugs (93.4%). CONCLUSIONS: This study shows the importance of including a clinical pharmacist in a multidisciplinary team in identifying and preventing DRPs in the hematology service.

[Risk factors associated to adverse drug events in hospitalized patients]. / Factores de riesgo asociados con eventos adversos a medicamentos en pacientes hospitalizados.

OBJECTIVE: To determine prevalence, causes and risk factors of ADE in hospitalized patients. METHODS: Analytical, observational, case-control study of patients with ADE. For statistical analysis, the following were calculated: percentages, frequencies, averages; odds ratio, χ2 test and multiple binary logistic regression. Data analysis was carried out with the Statistical Package, for the Social Sciences 23 program. RESULTS: A 132 patients were registered: 66 cases (26 EM and 40 RAM) and 66 controls; with average age of 35 years (SD 17.41). The prevalence of adverse drug events was 3.6%. The most frequently reported medications: antibiotics and anti-inflammatories. The frequency of adverse events by gender was: 39.3% men and 60.7% women. The services with the greatest patient care: emergencies, surgery; the most frequent route of administration: intravenous (32.3%). The main symptoms: skin. (32.3%) frequent symptoms: cutaneous. Associated symptoms RAM: type A pruritus (OR: 8.5; p = 0.001; IC95%: 0.035-0.393), type B pruritus (OR: 11; p = 0.001; CI95%: 0.021-0.368) urticaria (OR: 19; p = 0.005; IC95%: 0.007-0.412). Risk factors Associated EAM: female (OR: 2.6; p = 0.05; CI95%: 1.33-5.43), history of allergy (OR: 3.4; p = 0.033; CI95%: 1.04-8.40), prolonged hospital stays (OR: 5.4; p = 0.023; IC95%: 3.82-6.74). CONCLUSIONS: Patient safety is a priority when prescribing any drug, which represents a key point in prevention.

OBJETIVO: Determinar la prevalencia, causas y factores de riesgo asociados con eventos adversos a medicamentos en pacientes hospitalizados. MÉTODOS: Estudio de casos y controles, observacional, analítico, llevado a cabo en pacientes con eventos adversos a medicamentos. Para el análisis estadístico se calcularon: porcentajes, frecuencias, promedios; razón de momios, prueba de χ2 y regresión logística binaria múltiple. El análisis de los datos se efectuó con el programa Statistical Package, for the Social Sciencies 23. RESULTADOS: Se registraron 132 pacientes: 66 casos (26 EM y 40 RAM) y 66 controles, con edad promedio de 35 años (DS 17.41). La prevalencia de eventos adversos a medicamentos fue del 3.6%. Los medicamentos reportados con mayor frecuencia: antibióticos y antiinflamatorios. La frecuencia de eventos adversos por género fue: 39.3% hombres y 60.7% mujeres. Los servicios con mayor atención de pacientes: urgencias y cirugía; vía de administración más frecuente: intravenosa (32.3%). Los principales síntomas fueron los cutáneos. Los síntomas asociados con reacción adversa a medicamentos: prurito tipo A (RM: 8.5; p = 0.001; IC95%: 0.035-0.393), prurito tipo B (RM: 11; p = 0.001; IC95%: 0.021-0.368) urticaria (RM: 19; p = 0.005; IC95%: 0.007-0.412). Los factores de riesgo asociados con eventos adversos a medicamentos: mujer (RM: 2.6; p = 0.05; IC95%: 1.33-5.43), antecedente de alergia (RM: 3.4 p = 0.033; (IC95%: 1.04-8.40) y estancia hospitalaria prolongada (RM: 5.4; p = 0.023; IC95%: 3.82-6.74). CONCLUSIONES: La seguridad de los pacientes es una prioridad al momento de prescribir cualquier fármaco, lo que representa un punto clave en la prevención.

Gender Difference in sidE eFfects of ImmuNotherapy: a possible clue to optimize cancEr tReatment (G-DEFINER): study protocol of an observational prospective multicenter study.

BACKGROUND: Immune checkpoint inhibitors (ICIs) have significantly improved outcomes in various cancers. ICI treatment is associated with the incidence of immune-related adverse events (irAEs) which can affect any organ. Data on irAEs occurrence in relation to sex- differentiation and their association with gender-specific factors are limited. AIMS: The primary objective of the G-DEFINER study is to compare the irAEs incidence in female and male patients who undergo ICI treatment. Secondary objectives are: to compare the irAEs incidence in pre- and postmenopausal female patients; to compare the irAEs incidence in female and male patients according to different clinical and gender-related factors (lifestyle, psychosocial, and behavioral factors). Exploratory objectives of the study are to compare and contrast hormonal, gene-expression, SNPs, cytokines, and gut microbiota profiles in relation to irAEs incidence in female and male patients. METHODS AND RESULTS: The patients are recruited from Fondazione IRCCS Istituto Nazionale dei Tumori, Italy, St Vincent's University Hospital, Ireland, Oslo University Hospital, Norway, and Karolinska Insitutet/Karolinska University Hospital, Sweden. The inclusion of patients was delayed due to the Covid pandemic, leading to a total of 250 patients recruited versus a planned number of 400 patients. Clinical and translational data will be analyzed. INTERPRETATION: The expected outcomes are to improve the management of cancer patients treated with ICIs, leading to more personalized clinical approaches that consider potential toxicity profiles. The real world nature of the trial makes it highly applicable for timely irAEs diagnosis.

Factors associated with hematological adverse reactions of drugs authorized via the centralized procedure.

Serious hematological adverse drug reactions (HADRs) may lead to or prolong hospitalization and even cause death. The aim of this study was to determine the regulatory factors associated with HADRs caused by drugs that were authorized up to July 2023 by the European Medicines Agency (EMA) and to evaluate the frequency of HADRs. Using a cross-sectional approach, the type and frequency of HADRs were collected from the Summaries of Product Characteristics of Drugs Authorized by the EMA and analyzed within proprietary, nonproprietary, and biosimilar/biological frameworks. Multivariate statistical analysis was used to investigate the associations of generic status, biosimilar status, conditional approval, exceptional circumstances, accelerated assessment, orphan drug status, years on the market, administration route, and inclusion on the Essential Medicines List (EML) with HADRs. In total, 54.78% of proprietary drugs were associated with HADRs at any frequency, while anemia, leucopenia, and thrombocytopenia were observed in approximately 36% of the patients. The predictors of any HADR, anemia, and thrombocytopenia of any frequency are generic status, biosimilar status, and inclusion on the EML, while the only protective factor is the administration route. Biosimilars and their originator biologicals have similar frequencies of HADRs; the only exception is somatropin. Knowledge of the regulatory factors associated with HADRs could help clinicians address monitoring issues when new drugs are introduced for the treatment of patients.

Drug-related problems in cancer patients: A systematic review.

BACKGROUND: Cancer patients are at a significantly increased risk of drug-related problems due to multiple drugs. An inclusive review of drug-related problems would offer an approach for healthcare providers to decrease the frequency of drug-related problems in cancer patients. The purpose of this study was to assess all characteristic components of drug-related problems in cancer patients, and explore actions taken to resolve the detected drug-related problems the results could be used as a baseline for epidemiology and potential related risk factors for drug-related problems in cancer patients. METHODS: The present systematic review was done according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. The search consisted of studies listed from January 2015 and up to May 2023. A systematic review was carried out using an electronic database with a combination of Medical subject Headings of key words Medical Subject Heading terms. RESULTS: This evaluation included 17 studies from 11 different nations having 11 prospective and 6 retrospective studies. Pharmaceutical Care Network Europe classification system is the most commonly used to classify the drug-related problems. The prevalence of drug-related problems varied from 9.6% to 92.8%. The key predictors of the drug-related problems were age, polypharmacy, multiple comorbidities, and the stage of the disease. CONCLUSION: Drug-related problems are significantly more common among cancer patients. The age, polypharmacy, multiple comorbidities, and the stage of the malignancy all enhance the risk of acquiring drug-related problems. This review raises awareness of drug-related problems, encourages their early detection, and emphasizes the necessity for framing effective drug-related problem management strategies which will enhance patient care.

Pharmacoeconomics of medicines used for geriatric individuals in a tertiary care hospital in Delhi.

BACKGROUND OBJECTIVES: Expenditure on healthcare is a major concern in the geriatric age group. The current study was carried out to assess the expenditure patterns on medicines utilized in geriatric inpatients. METHODS: An observational study was conducted on 1000 geriatric inpatients, aged ≥60 yr, admitted to the medicine unit. Data were collected regarding demographic characteristics, prescribed medicines, expenditure incurred on medicines, appropriateness of medicines prescribed and adverse drug reactions (ADRs). Appropriateness of the prescribed medicines was determined using the American Geriatrics Society 2015 Updated Beers Criteria. RESULTS: Geriatric inpatients comprised 41.3 per cent of the total individuals admitted in the ward during the study period. A total of 8366 medicines were prescribed in 127 formulations. The total expenditure on prescribed medicines was INR 1,087,175 with a per capita expenditure of INR 1087.17. Parenteral medicines accounted for 91 per cent of the expenditure on medicines. Maximum expenditure (70%) was incurred on 11.9 per cent of the medicines prescribed. The per capita expenditure was significantly higher in individuals with comorbidities (P=0.03) and those who had a longer duration of hospital stay (P<0.0001). About 28.1 per cent prescriptions were inappropriate. ADRs (140) were observed in 139 (13.9%) inpatients. Individuals with inappropriate medicines prescriptions and ADRs had a longer duration of hospital stay and more number of medicines prescribed. INTERPRETATION CONCLUSIONS: Comorbidities, prolonged hospitalization, polypharmacy, inappropriate medicines and parenteral medicines being prescribed contribute to increased expenditure on medicines in geriatric inpatients. In view of the rising number of geriatric inpatients, there is a need to frame a drug policy for them along with surveillance of expenditure on prescribed medicines. This needs to be treated as a priority.

A Real-world Toxicity Atlas Shows that Adverse Events of Combination Therapies Commonly Result in Additive Interactions.

PURPOSE: Combination therapies are a promising approach for improving cancer treatment, but it is challenging to predict their resulting adverse events in a real-world setting. EXPERIMENTAL DESIGN: We provide here a proof-of-concept study using 15 million patient records from the FDA Adverse Event Reporting System (FAERS). Complex adverse event frequencies of drugs or their combinations were visualized as heat maps onto a two-dimensional grid. Adverse event frequencies were shown as colors to assess the ratio between individual and combined drug effects. To capture these patterns, we trained a convolutional neural network (CNN) autoencoder using 7,300 single-drug heat maps. In addition, statistical synergy analyses were performed on the basis of BLISS independence or χ2 testing. RESULTS: The trained CNN model was able to decode patterns, showing that adverse events occur in global rather than isolated and unique patterns. Patterns were not likely to be attributed to disease symptoms given their relatively limited contribution to drug-associated adverse events. Pattern recognition was validated using trial data from ClinicalTrials.gov and drug combination data. We examined the adverse event interactions of 140 drug combinations known to be avoided in the clinic and found that near all of them showed additive rather than synergistic interactions, also when assessed statistically. CONCLUSIONS: Our study provides a framework for analyzing adverse events and suggests that adverse drug interactions commonly result in additive effects with a high level of overlap of adverse event patterns. These real-world insights may advance the implementation of new combination therapies in clinical practice.

Rising cases of drug-induced pulmonary fibrosis: Analysis of the Food and Drug Administration Adverse Event Reporting System (FAERS) database, 2000-2022.

PURPOSE: Pulmonary fibrosis (PF) is a severe, progressive disease, which may be caused by exposure to certain medications. METHODS: We queried the U.S. FDA Adverse Event Reporting System (FAERS) from 2000 to 2022, using the search terms "pulmonary fibrosis" and "idiopathic pulmonary fibrosis" and excluded reports with patients under the age of 18 years, and patients with unknown sex or age. Reports were sorted by generic drug names, counted, and plotted over time using a best-fit trendline based on an exponential function. RESULTS: From 2000 to 2022, there were 24 095 935 adverse drug events reported in FAERS, of which 17 520 (0.07%) were reported as PF. After excluding reports containing patients with unknown age (5255, 30%), sex (122, 0.7%), and age below 18 years old (155, 0.9%), our study included 11 988 reports. The mean age of the study sample was 66.5 ± 13.1 years, and 6248 patients (52.1%) were male. Plotting the 11 988 reports by year revealed an exponential best fit line (R2 = 0.88) with a positive slope over time. The top five drug classes associated with PF were disease modifying antirheumatic drugs (DMARDs, 39.4%), antineoplastic agents (26.4%), cardiovascular agents (12.6%), corticosteroids (4.6%), and immunosuppressive agents (4.0%). CONCLUSION: A 23-year analysis of the FAERS database revealed exponentially increasing adverse event reports of PF. Significant annual increases in reporting of PF suspected with DMARDs and antineoplastic agents were identified. Our study highlights important trends, which should be used to guide PF research related to drugs of potential importance.

Postmarket safety communications on drugs approved in Japan: A 25-year analysis.

Drug safety communications (DSCs) are essential tools for communicating important postmarket serious drug safety information to healthcare professionals and patients. Previous studies characterized DSCs issued by the U.S. Food and Drug Administration (FDA) and the European Medicines Agency (EMA); however, knowledge about the activities of the Pharmaceuticals and Medical Devices Agency (PMDA)/the Ministry of Health, Labor and Welfare (MHLW) is limited. This study characterized DSCs by the PMDA/MHLW in comparison with previously reported DSCs by the FDA and the EMA. We retrospectively analyzed 37 DSCs of 41 adverse drug reactions (ADRs) for 33 drugs in Japan from 1997 to 2022. Most DSCs were related to non-oncology drugs (30/37, 81.1%), and the median (interquartile range) time from approval to DSC issuance was 19 (10-51) months. Notably, the regulatory review reports and the latest labels before DSC issuance did not describe 16/28 (57.1%) and 12/37 (32.4%) of the ADRs related to DSCs, respectively. Most DSCs resulted in label revisions (36/37, 97.3%) and seven drugs were eventually withdrawn. Some DSC characteristics are similar among the PMDA/MHLW, the FDA, and the EMA; however, the number, contents, and range of new safety issues addressed by DSCs differ among the three jurisdictions. Our study emphasized the importance of continuous efforts to gather postmarket drug safety information because substantial ADRs that led to DSCs were recognized after approval and were associated with critical label revisions and withdrawals. Future studies are required to address global challenges for regulatory harmonization of safety-related regulatory actions.

Individualized prevention of proton pump inhibitor related adverse events by risk stratification.

Proton pump inhibitors (PPIs) are commonly used for gastric acid-related disorders, but their safety profile and risk stratification for high-burden diseases need further investigation. Analyzing over 2 million participants from five prospective cohorts from the US, the UK, and China, we found that PPI use correlated with increased risk of 15 leading global diseases, such as ischemic heart disease, diabetes, respiratory infections, and chronic kidney disease. These associations showed dose-response relationships and consistency across different PPI types. PPI-related absolute risks increased with baseline risks, with approximately 82% of cases occurring in those at the upper 40% of the baseline predicted risk, and only 11.5% of cases occurring in individuals at the lower 50% of the baseline risk. While statistical association does not necessarily imply causation, its potential safety concerns suggest that personalized use of PPIs through risk stratification might guide appropriate decision-making for patients, clinicians, and the public.

Adverse events related to drug-drug interactions in COVID-19 patients. A persistent concern in the post-pandemic era: a systematic review.

INTRODUCTION: Since COVID-19 patients are often polytreated, monitoring drug-drug interaction (DDIs) is necessary. We evaluated whether drugs used after the second COVID-19 pandemic wave were associated with DDI-related adverse events and the role of drug interaction checkers in identifying them. METHODS: The study (PROSPERO-ID: CRD42024507634) included: 1) consulting the drug interaction checkers Drugs.com, Liverpool COVID-19 Interactions, LexiComp, Medscape, and Micromedex; 2) systematic review; 3) reviewed studies analysis; 4) evaluating drug interaction checkers potential to anticipate DDI-related adverse events.The systematic review was performed searching PubMed, Scopus, ScienceDirect, and Cochrane databases from 1 March 2022 to 11 November 2023. Observational studies, and clinical trials were included. Article without reporting direct association between DDIs and adverse events were excluded. The risk of bias was assessed by Newcastle-Ottawa scale. RESULTS: The most frequent DDIs involved nirmatrelvir/ritonavir (N/R) and fluvoxamine. Fifteen studies, including 150 patients and 35 DDI-related outcomes, were analyzed. The most frequent DDIs involved tacrolimus with N/R, resulting in creatinine increase.Eighty percent of reported DDI-related adverse events would have been identified by all drug-interaction checkers, while the remaining 20% by at least 2 of them. CONCLUSIONS: Drug interaction checkers are useful but show inconsistencies. Multiple sources are needed to tailor treatment in the context of COVID-19.

Comparative analysis of adverse drug reactions associated with new antiseizure medications from the Korea Adverse Event Reporting System database.

OBJECTIVE: This study aimed to compare and characterize the safety profiles of new antiseizure medications (ASMs) using a nationwide pharmacovigilance database from a long-term perspective in Korea. METHODS: We reviewed adverse event reports from the Korea Adverse Event Reporting System database between January 2013 and December 2022 for descriptive analysis of six new ASMs (lacosamide, levetiracetam, lamotrigine, oxcarbazepine, topiramate, and zonisamide). We investigated the frequency and characteristics of adverse drug reactions (ADRs) based on the MedDRA terminology, system organ classes, and modified WHO classification. RESULTS: We identified 5,733 reported cases of ADRs. The commonly reported ADRs associated with total ASMs were rash/urticaria (1,822, 31.8 %), dizziness (409, 7.1 %), somnolence/drowsiness (311, 5.4 %), and hepatotoxic effects (273, 4.8 %). Type B (idiosyncratic) effects (2,932; 51.1 %) were more commonly reported than Type A (related to known drug mechanisms) effects (2,613; 45.6 %). Skin and subcutaneous tissue disorders and type B effects were most commonly reported for lamotrigine and oxcarbazepine, whereas nervous system disorders and type A effects were most commonly reported for lacosamide, topiramate, and zonisamide. The pediatric group (<18 years) exhibited skin and subcutaneous tissue disorders and type B effects relatively more frequently than the adult and older adult groups. CONCLUSION: Hypersensitivity skin reactions and type B effects remained significant ADRs in the new ASMs; however, type A effects were more commonly reported in some ASMs. The pediatric group showed a higher rate of type B effects. Overall, new ASMs should also be used with caution.

Identification and Characterization of Immune Checkpoint Inhibitor-Induced Toxicities From Electronic Health Records Using Natural Language Processing.

PURPOSE: Immune checkpoint inhibitors (ICIs) have revolutionized cancer treatment, yet their use is associated with immune-related adverse events (irAEs). Estimating the prevalence and patient impact of these irAEs in the real-world data setting is critical for characterizing the benefit/risk profile of ICI therapies beyond the clinical trial population. Diagnosis codes, such as International Classification of Diseases codes, do not comprehensively illustrate a patient's care journey and offer no insight into drug-irAE causality. This study aims to capture the relationship between ICIs and irAEs more accurately by using augmented curation (AC), a natural language processing-based innovation, on unstructured data in electronic health records. METHODS: In a cohort of 9,290 patients treated with ICIs at Mayo Clinic from 2005 to 2021, we compared the prevalence of irAEs using diagnosis codes and AC models, which classify drug-irAE pairs in clinical notes with implied textual causality. Four illustrative irAEs with high patient impact-myocarditis, encephalitis, pneumonitis, and severe cutaneous adverse reactions, abbreviated as MEPS-were analyzed using corticosteroid administration and ICI discontinuation as proxies of severity. RESULTS: For MEPS, only 70% (n = 118) of patients found by AC were also identified by diagnosis codes. Using AC models, patients with MEPS received corticosteroids for their respective irAE 82% of the time and permanently discontinued the ICI because of the irAE 35.9% (n = 115) of the time. CONCLUSION: Overall, AC models enabled more accurate identification and assessment of patient impact of ICI-induced irAEs not found using diagnosis codes, demonstrating a novel and more efficient strategy to assess real-world clinical outcomes in patients treated with ICIs.

A review of real-world evidence on preemptive pharmacogenomic testing for preventing adverse drug reactions: a reality for future health care.

Adverse drug reactions (ADRs) are a significant public health concern and a leading cause of hospitalization; they are estimated to be the fourth leading cause of death and increasing healthcare costs worldwide. Carrying a genetic variant could alter the efficacy and increase the risk of ADRs associated with a drug in a target population for commonly prescribed drugs. The use of pre-emptive pharmacogenetic/omic (PGx) testing can improve drug therapeutic efficacy, safety, and compliance by guiding the selection of drugs and/or dosages. In the present narrative review, we examined the current evidence of pre-emptive PGx testing-based treatment for the prevention of ADRs incidence and hospitalization or emergency department visits due to serious ADRs, thus improving patient safety. We then shared our perspective on the importance of preemptive PGx testing in clinical practice for the safe use of medicines and decreasing healthcare costs.

Real-world safety of Levetiracetam: Mining and analysis of its adverse drug reactions based on FAERS database.

INTRODUCTION: Levetiracetam is a relatively new and widely utilized anti-seizure medication; however, limited information is available regarding its adverse effects. This study aims to thoroughly investigate, evaluate, and present evidence on the safety profile of Levetiracetam, relying on data from the FDA Adverse Event Reporting System (FAERS) database to facilitate informed clinical decision-making. METHODS: We employed various statistical measures, including Reporting Odds Ratio (ROR), Proportionate Reporting Ratio (PRR), and analysis by the Medicines and Healthcare Products Regulatory Agency (MHRA), to identify signals of adverse reactions associated with Levetiracetam. Positive signals consistent with Designated Medical Event (DME) were singled out for focused comparison and discussion. RESULTS: The analysis of 26,182 adverse events linked to Levetiracetam as the primary suspected drug revealed 692 positive signals spanning 22 System Organ Classes (SOCs). Nervous system disorders were the most frequently reported, followed by psychiatric disorders, and general disorders and administration site conditions. 11 positive signals consistent with Preferred Terms (PTs) in DME were identified, predominantly concentrated in 6 SOCs. Among these, rhabdomyolysis, Stevens-Johnson syndrome (SJS), toxic epidermal necrolysis (TEN), drug reaction with eosinophilia and systemic symptoms (DRESS) exhibited relatively large values of A, ROR, and Chi-squared. Additionally, PTs related to spontaneous abortion, drug interaction, urethral atresia, ventricular septal defect, and atrial septal defect showed significant strength. CONCLUSIONS: The study indicates that Levetiracetam carries a potential risk of causing rhabdomyolysis, SJS, TEN, DRESS as well as spontaneous abortion. Signals related to drug interaction, urethral atresia, ventricular septal defect, and atrial septal defect warrant heightened attention in clinical use.