Assessing the real-world safety of tralokinumab for atopic dermatitis: insights from a comprehensive analysis of FAERS data
Ontology highlight
ABSTRACT:
SUBMITTER: Zhao K
PROVIDER: S-EPMC11347326 | biostudies-literature | 2024 Jan
REPOSITORIES: biostudies-literature
Similar Datasets
Project description:ObjectiveThe intravitreal dexamethasone implant (Dex) is widely used for various ocular conditions, including diabetic macular edema (DME), retinal vein occlusion (RVO), and non-infectious uveitis. Despite its efficacy, concerns remain regarding its safety profile. This study aims to analyze the adverse events (AEs) associated with Dex reported in the FDA Adverse Event Reporting System (FAERS) database from 2010 to 2024.MethodsData were extracted from FAERS, focusing on cases where Dex was the primary suspect drug. The dataset was processed to eliminate duplicates and incomplete entries. Disproportionality analysis, including Reporting Odds Ratio (ROR) and Proportional Reporting Ratio (PRR), was used to detect safety signals. AEs were categorized by system organ class (SOC) and preferred term (PT).ResultsA total of 1,588 adverse event reports (AERs) were analyzed, revealing a significant upward trend. The Eye disorders was the most commonly reported SOC, with strong disproportionality signals (ROR: 45.11; PRR: 23.71). Key AEs identified at the PT level included Corneal decompensation, Choroidal hematoma, and Posterior capsule rupture, which were not listed on the drug label. Considering the reported numbers, the Endophthalmitis was the most common AE. Additionally, a significant proportion of AEs were observed within the first seven days post-administration, emphasizing the need for monitoring.ConclusionWhile Dex remains an effective treatment option for ocular conditions, its use is associated with significant risks, particularly regarding unexpected and severe complications such as corneal decompensation. Continuous pharmacovigilance and detailed patient monitoring are essential to mitigate these risks. Future studies should focus on prospective designs and comprehensive clinical data to better understand the safety profile of Dex.
| S-EPMC11809023 | biostudies-literature
Project description:IntroductionThe diagnosis and management of atopic dermatitis (AD) is extensively addressed in detailed clinical guidelines. However, the high heterogeneity regarding presentation and progression and the increasingly broad therapeutic landscape suggest a complex real-world scenario, leading to multiple trajectories of AD patients.MethodsUsing a Delphi methodology for assessing the degree of consensus, we explored the views of a panel of dermatologists regarding the patients' trajectory through the diagnosis (block 1), treatment (block 2), and long-term management (block 3) of AD. Based on a systematic search of the literature, a scientific committee prepared a questionnaire of relevant items that were rated on a 10-point scale (from "totally agree" to "totally disagree") by a panel of dermatologists attending patients with AD in the hospital setting. Consensus was established based on predefined rules.ResultsThe final questionnaire included 58 items and was answered by 17 dermatologists. Overall, consensus was reached on 22 items (37.9%), each of which was a consensus for agreement. The consensus rates in blocks 1, 2, and 3 were 22.7%, 19.0%, and 86%, respectively.ConclusionsOur analysis revealed a remarkable lack of consensus on various aspects of the routine diagnosis and treatment of AD. These findings suggest the presence of unmet needs or limited implementation of guidelines for the management of AD and encourage further research to explore the causes of this low consensus on the management of AD in the real-world setting.
| S-EPMC8484426 | biostudies-literature
Project description:ImportanceOlder adults with atopic dermatitis (AD) face unique treatment challenges, including comorbidities, polypharmacy, and a higher risk for infections (eg, herpes zoster). Furthermore, limited data are available from clinical trials for treatments in this population. In phase 3 studies, tralokinumab showed superior efficacy in moderate-to-severe AD vs placebo, but results were not stratified by age group.ObjectiveTo evaluate the safety and efficacy of tralokinumab in older (≥65 years) patients with moderate-to-severe AD.Design, setting, and participantsA post hoc analysis for adults 65 years or older was conducted from a subset of patients in the US, Canada, Europe, and Asia in 3 randomized, placebo-controlled, phase 3 trials (ECZTRA 1 and 2 [monotherapy] and ECZTRA 3 [tralokinumab + topical corticosteroids as needed]). The post hoc data were analyzed in 2022.Main outcomes and measuresPooled data from up to 16 weeks of treatment from ECZTRA 1, 2, and 3 were used to assess safety. Statistical analyses followed prespecifications of primary end points. Separate efficacy analyses were conducted in these trials respectively at 16 weeks.ResultsA total of 75 older adults (42 women [56%]) treated with tralokinumab from the ECZTRA 1, 2, and 3 trials were included in this post hoc analysis. Similar proportions of patients reported adverse events (AEs) with tralokinumab and placebo (44 [58%]). Three patients (4%) in the tralokinumab arm and 3 (10.3%) in the placebo arm experienced severe AEs, and 4 (5.3%) and 2 (6.9%), respectively, had AEs leading to discontinuation. More patients achieved 75% or greater improvement in Eczema Area and Severity Index scores with tralokinumab than placebo (33.9% vs 4.8%; P < .001) in ECZTRA 1 and 2. Similar trends, although not statistically significant, were seen in ECZTRA 3. Safety and efficacy outcomes in this population were similar compared with the younger patient cohorts. The small sample size limited generalizations from this analysis.Conclusion and relevanceThe results of this post hoc analysis suggest that tralokinumab is well tolerated and efficacious in patients 65 years or older with moderate-to-severe AD.
| S-EPMC10448370 | biostudies-literature
Project description:The phenotypes of atopic dermatitis (AD) are diverse, and ethnic differences have been suggested. To date, few studies have explored large-scale national data on the treatment patterns of AD in Asians. Therefore, we aimed to examine real-world treatment patterns for AD, including the probability of discontinuation of AD treatment and restart after discontinuation. A retrospective observational study was conducted using the nationwide healthcare database in South Korea between January 1, 2016 to July 31, 2020. We identified 944,559 pediatric patients and 1,066,453 adults with AD. Topical corticosteroids and antihistamines were the most commonly prescribed medications in all age groups. The frequency of topical corticosteroid prescription decreased as the age increased. Although immunosuppressive drugs were not widely used in both children and adults, cyclosporine was the most frequently prescribed immunosuppressant, particularly among those aged 12 years or more (1-2%). Pediatric patients were more likely to discontinue treatment than adult patients. Treatment restart for moderate-to-severe AD was earlier than that for overall AD. In conclusion, significant differences were observed in the treatment patterns of AD between pediatric and adult patients. These findings will improve our understanding of the latest treatment patterns for AD, which may contribute to decision-making in clinical practice.
| S-EPMC9365828 | biostudies-literature
Project description:Atopic dermatitis (AD) is characterized by a complex epidermal barrier deficiency and exaggerated immune responses dominated by type-2-mechanisms with variable contributions of additional immune axes. Interleukin (IL)-13 is overexpressed in AD skin and a key driver of both barrier dysfunction and inflammation. We here prospectively studied the effects of IL-13 inhibition with tralokinumab on cutaneous transcriptome profiles using RNA sequencing of biopsies from 16 moderate-to-severe AD patients obtained at baseline, week 2 and week 16. Tralokinumab therapy induced early and delayed expression changes, and progressively shifted the transcriptomic profile of lesional towards non-lesional skin by modulating both genes associated with keratinocyte proliferation and differentiation, itch signaling, and downstream inflammatory responses. At week 16, 751 genes were still significantly dysregulated as compared to healthy control skin, reinforcing the need for long-term immunomodulatory therapy of moderate to severe AD to achieve deep responses. The study was registered with ClinicalTrials.gov (NCT04556461)
2024-12-19 | GSE277961 | GEO
Project description:BackgroundTralokinumab, the first fully human monoclonal antibody that binds specifically to interleukin-13, was safe and effective for treating atopic dermatitis (AD) in clinical trials, but real-life experience is still limited.ObjectivesThe objective of this study was to evaluate the effectiveness and safety of tralokinumab in severe AD in a real-life multicenter prospective cohort.MethodsAdult patients with severe AD were enrolled between January 2022 and July 2022 and received tralokinumab subcutaneously for 16 weeks. Objective and subjective scores were collected at baseline, weeks 6 and 16. Adverse events were reported throughout the study.ResultsTwenty-one patients were included. An improvement of at least 75% on the Eczema Area and Severity Index (EASI 75) was achieved in 66.7% of patients at week 16. The median objective and subjective scores at week 16 were significantly (p < 0.001) lower than those at baseline. Combination with cyclosporine was sometimes necessary at the beginning of treatment, and addition of upadacitinib was required for some patients with very severe disease during the treatment. The most frequent adverse events were flares of eczema (23.8%) and reactions at injection site (19.0%). No cases of conjunctivitis were reported. Four patients (19.0%) discontinued treatment.ConclusionsTralokinumab is an effective first-line biotherapy for severe AD. However, therapeutic response may be progressive. Safety data were reassuring. Atopic dermatitis flares or reactions at the injection site may lead to discontinuation of treatment. A history of conjunctivitis on dupilumab is not a contraindication to the initiation of tralokinumab.
| S-EPMC10097792 | biostudies-literature
Project description:AimsNeratinib has emerged as significant theraputic option for breast cancer treatment. However, despite its approval, numerous adverse drug events (ADEs) associated to it remain unrecognized and unreported. This study aims to mine and analyze the signals of ADEs related to neratinib from the US Food and Drug Administration Adverse Event Reporting System (FAERS) database, providing insights for safe and rational clinical use of drug.MethodsAll the neratinib-related ADEs data were collected from FAERS database from the third quarter (Q3) of 2017 to the fourth quarter (Q4) of 2023. After standardizing the data, 4 disproportionality methods were used to assess the correlation between neratinib and ADEs.ResultsOf the 1,544 ADEs implicating neratinib as the primary suspected drug, a combined total of 48 preferred terms (PTs) and 10 system organ classes (SOCs) showed significant disproportionality accross all four algorithms simultaneously. These SOCs included gastrointestinal disorders (n = 2,564, ROR 7.14), general disorders and administration site conditions (n = 958, ROR 0.77) and injury poisoning and procedural complications (n = 474, ROR 0.58) among others. Upon comparison with the neratinib manual, 34 ADEs not documented in the manual were found at the PT level.ConclusionOur study provide new real-world evidence for drug safety information of neratinib. While the majority of our findings were aligned with the information provided in the manual. We identified additional ADEs not previously documented. Consequently, further studies are needed to validate unreported ADEs to ensure the efficacy and safety of neratinib for patients.
| S-EPMC11427278 | biostudies-literature
Project description:Tralokinumab is the first biologic therapy for moderate-to-severe atopic dermatitis (AD) that specifically neutralizes interleukin-13 activity, a key driver of AD signs and symptoms. Tralokinumab is a human immunoglobulin G4 monoclonal antibody administered subcutaneously every 2 weeks (with possibility of maintenance dosing every 4 weeks). This population pharmacokinetic (PK) analysis aimed to identify sources of PK variability and relevant predictors of tralokinumab exposure in adults with moderate to severe AD. Nonlinear mixed-effect modeling, including covariate analysis, was used on a data set including 2561 subjects (AD, asthma, healthy) from 10 clinical trials. A 2-compartment model with first-order absorption and elimination adequately described the tralokinumab PK. Body weight was identified as a relevant predictor of tralokinumab exposure; other covariates including age, sex, race, ethnicity, disease type, AD severity, and renal and hepatic impairment were not. For body weight, the difference in exposure between the upper- and lower-weight quartiles in patients with AD was <2-fold, supporting the appropriateness of flat dosing (300 mg). Given the reduced exposure associated with higher body weight, coupled with the reduced exposure provided by dosing every 4 weeks, it is uncertain whether higher-weight patients will achieve sufficient exposure to maintain efficacy if dosed every 4 weeks instead of the standard every 2 weeks.
| S-EPMC9796478 | biostudies-literature
Project description:BackgroundOfatumumab, a fully human monoclonal antibody targeting CD20, is approved for the treatment of relapsing multiple sclerosis. Comprehensive real-world safety data are crucial for informing clinical practice.MethodsThe FDA Adverse Event Reporting System database was utilized to perform a disproportionality analysis, covering reports from Q3 2020 to Q2 2024, in which ofatumumab was identified as the primary suspected drug. Statistical approaches used included the Reporting Odds Ratio, Proportional Reporting Ratio, Bayesian Confidence Propagation Neural Network, and Multi-item Gamma Poisson Shrinker. The timing of adverse events was assessed using the Weibull distribution model to highlight temporal risk patterns.ResultsKnown adverse reactions, such as injection site reactions and upper respiratory tract infections, displayed positive signals. Additionally, novel off-label adverse events, including brain fog, muscle spasms, and mood alterations, were identified, marking the first real-world evidence of these potential risks. Temporal analysis revealed that most adverse events occurred within the first month of treatment, indicating an early risk phase. Subgroup analysis demonstrated notable differences in adverse event profiles by gender and age, with males more prone to hyperhidrosis and older patients more susceptible to neurological symptoms.ConclusionThis real-world analysis of ofatumumab provides important safety insights, confirming known adverse reactions and identifying additional potential risks. Early and tailored monitoring protocols during the initial treatment phase, including regular neurological and psychiatric assessments, are recommended to optimize patient safety and outcomes. Prospective studies are recommended to validate these results and explore the underlying mechanisms.
| S-EPMC11799251 | biostudies-literature
Project description:BackgroundSorafenib is approved for the targeted therapy of cancers such as liver cancer and renal cancer. Given its widespread use, drug-related adverse events have received attention, and the post-marketing regulatory link is crucial.ObjectiveBy using the FAERS database to mine the adverse events (AEs) related to sorafenib, comparing the association intensity of key AEs, and exploring potential drug-related AEs, it provides a reference for clinical medication.MethodsCollect ADE data related to sorafenib in the FAERS database from 2006 to 2023. Standardize the data, and map adverse events to system organ classes and preferred terms. Analyze using various signal quantification techniques such as ROR, PRR, BCPNN, and MGPS.ResultsAmong 18,520 adverse event reports (AERs) where sorafenib was the primary suspected drug, a total of 390 preferred terms (PTs) of adverse reactions were identified, covering 24 different system organ classes (SOCs). Specifically, the adverse events of sorafenib mainly involve the digestive system, skin and subcutaneous tissue, as well as non-specific physical discomfort including infection and injury. Among them, digestive system symptoms and skin toxicity are typical adverse reactions of sorafenib. We also observed uncommon but clearly strong AE signals, such as chloracne (n = 3, ROR 1756.39, PRR 1756.32, IC 8.78, EBGM 439.83), low-differentiated thyroid cancer (n = 4, ROR 585.47, PRR 585.44, IC 8.2, EBGM 293.22). It is worth noting that palmar-plantar erythrodysaesthesia syndrome (n = 2109, ROR 73.98, PRR 72.03, IC 6.01, EBGM 64.25) and hepatic encephalopathy (n = 457, ROR 37.44, PRR 37.23, IC 5.13, EBGM 35.07) have a higher incidence and signal intensity. In addition, we also observed some adverse events not mentioned in the official drug instructions, such as vitamin K deficiency or increased protein induced by antagonist II (PIVKA-II), abnormal alpha-fetoprotein, tumor metastasis, and splenic atrophy.ConclusionSorafenib carries the risk of various adverse reactions while providing therapeutic effects. In clinical applications, physicians should closely monitor the occurrence of digestive system reactions, skin lesions, endocrine system lesions, as well as injuries, infections, and other events.
| S-EPMC11416516 | biostudies-literature