Search Results (1,595)

Background/Objectives: Concerns regarding the psychiatric safety profile of glucagon-like peptide-1 receptor agonists (GLP-1 RAs) have increased since the 2023 European Medicines Agency (EMA) and U.S. Food and Drug Administration (FDA) reviews. However, it remains unclear whether this signal is uniform across the drug class or concentrated in specific compounds. This study aimed to characterize and compare, in a systematic manner, the global reporting patterns of psychiatric adverse drug reactions (ADRs) associated with the main GLP-1 RAs using the World Health Organization (WHO) VigiBase global pharmacovigilance database. Methods: A descriptive, cross-sectional pharmacovigilance study was conducted on individual case safety reports (ICSRs) retrieved from VigiAccess (January 2000–2026) for semaglutide, liraglutide, dulaglutide, exenatide, tirzepatide, and lixisenatide. A disproportionality analysis was performed within the MedDRA “Psychiatric disorders” System Organ Class (SOC) using the Reporting Odds Ratio (ROR) with 95% confidence intervals (CIs). This study adhered to the STROBE and READUS-PV guidelines. Results: A total of 537,519 ADR reports were analyzed across the five drugs with sufficient reporting volume (lixisenatide was excluded owing to n = 22 psychiatric events). Psychiatric disorders accounted for 24,899 reports, with marked intraclass heterogeneity in both the proportion of psychiatric reports (6.73% for semaglutide versus 3.12% for tirzepatide) and in disproportionality estimates. Signals of disproportionate reporting were identified exclusively for semaglutide (ROR 1.55; 95% CI 1.50–1.59) and liraglutide (ROR 1.19; 95% CI 1.15–1.23), whereas tirzepatide, dulaglutide, and exenatide showed point estimates below unity. Conclusions: The psychiatric safety profile of GLP-1 RAs is not homogeneous within the therapeutic class. The disproportionality signal is concentrated on semaglutide and, to a lesser extent, liraglutide. These findings extend previous WHO-based analyses limited to suicidality and support active clinical surveillance of psychiatric symptoms in patients treated with these specific agents. Full article

Elite athletes experience diverse biological, psychological, and social challenges during injury rehabilitation, yet few qualitative studies have explored these experiences and their interactions from a biopsychosocial perspective. This exploratory qualitative study investigated the biopsychosocial experiences of elite athletes during injury rehabilitation and the interactions among these experiences through semi-structured interviews with five participants, using inductive content analysis. Athletes reported biological experiences including musculoskeletal symptoms, limitations in daily activities, adverse drug reactions, psychosomatic symptoms, and physical development; psychological experiences including negative emotions (anger, anxiety, and depression) and positive experiences (restoration and psychological resilience); and social experiences including informational, instrumental, and emotional support, as well as negative social influences such as blame and pressure to return to play. Participants perceived that these biological, psychological, and social experiences were closely interconnected throughout rehabilitation. Biological experiences, such as pain and physical impairment, were perceived to contribute to negative emotions, including anxiety, whereas negative emotions were associated with stress-related psychosomatic symptoms, such as gastrointestinal symptoms and headaches. Emotional support was associated with positive emotional experiences, whereas negative social influences, including blame and pressure to return to play, were associated with negative emotional responses. These findings contribute to an understanding of the multidimensional experiences of injured elite athletes and may inform development of integrated rehabilitation approaches that address biological, psychological, and social aspects of recovery. Full article

Background: Personalized precision medicine adapts therapeutic strategies to individual characteristics. In psychiatry, suboptimal outcomes with antipsychotics are often related to adverse drug reactions, poor adherence and therapeutic failure. Pharmacogenetics, particularly CYP2D6 genotyping, can improve clinical outcomes through genotype-guided therapy. This study aimed to design and implement a pharmacogenomic and pharmacokinetic testing program for long-acting injectable (LAI) antipsychotics within the Galician Health Service to enhance personalized psychiatric care. Methods: The pilot program encompasses pharmacogenetic and pharmacokinetic testing. Inclusion criteria were broad, covering patients initiating or receiving LAI antipsychotic therapy, as well as those with prior adverse reactions in order to explore scenarios where pharmacogenetic and/or pharmacokinetic data could help with clinical decisions. Structured workflows, interdisciplinary training and integration of results into the electronic health record supported implementation. A pharmacogenetic panel was specifically designed for psychiatric care, targeting clinically relevant variants in CYP2D6, CYP3A4 and ABCB1. Results: A total of 540 patients were included, with primary testing reasons being clinical follow-up (54.6%) and oral-to-LAI transition (38.5%). The CYP2D6 phenotypes were 55% normal, 34% intermediate, 6.3% poor and 4.3% ultrarapid metabolizers. Atypical metabolism was observed in 6.7% of patients for CYP3A4 and in over half for ABCB1. Plasma drug levels were within the therapeutic range for most patients, though some measurements were above or below expected values. Conclusions: This pilot demonstrates a scalable, evidence-based approach to precision psychiatry for LAI antipsychotics, integrating pharmacogenetic and pharmacokinetic testing into routine care. The framework facilitates genotype-guided decision-making and supports broader adoption of pharmacogenomics in psychiatric practice. Full article

Background/Objectives: Cutaneous adverse drug reactions (CADRs) account for approximately 45% of all adverse drug reactions. Although most are self-limiting, some may progress to severe cutaneous adverse reactions (SCARs). In children, delayed rashes associated with antimicrobial therapy, particularly beta-lactams, are often misclassified as drug allergies, leading to unnecessary antibiotic avoidance and potentially suboptimal antimicrobial prescribing. This study aimed to characterize delayed antimicrobial-associated CADRs in children and to investigate reporting patterns and factors associated with their clinical management across age groups. Methods: Real-world data from pediatric patients hospitalized in 2023 at the “Ospedale dei Bambini Vittore Buzzi” (Milan, Italy) were integrated with Individual Case Safety Reports from the FDA Adverse Event Reporting System (FAERS). Only cases with documented treatment durations were included. Clinical characteristics, antimicrobial exposure patterns, and factors associated with the reporting of delayed rashes were evaluated. Results: Five pediatric patients developed delayed CADRs after 19–22 days of antimicrobial therapy. Infectious and immunological investigations were negative, and symptoms resolved following drug discontinuation. FAERS analysis identified 97 delayed rash reports, associated with prolonged treatment duration, frequent polytherapy, and higher reporting rates for vancomycin, teicoplanin, and beta-lactam combination regimens. Logistic regression showed that age and polypharmacy were significantly associated with reporting patterns of delayed rash and therapy continuation among reported cases. Conclusions: Among reported cases, delayed antimicrobial-associated CADRs were associated with age and polypharmacy. Improved recognition of these reactions may facilitate appropriate clinical management, support more informed prescribing decisions, and reduce inappropriate antibiotic allergy labeling. Further studies are needed to validate these findings and refine risk-based management strategies in pediatric patients. Full article

Background/Objectives: Pharmacovigilance workflows rely heavily on unstructured text across diverse sources. Here, we systematically reviewed how large language models (LLMs) are being explored as support tools for adverse drug reaction (ADR) detection, extraction, triage, and documentation, highlighting their potential for precision medicine and big data-enabled safety monitoring. Methods: Following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses 2020 guidelines, we systematically searched PubMed, Scopus, and Web of Science for studies published between January 2022 and March 2026. Ultimately, 83 empirical studies satisfied the inclusion criteria. A narrative synthesis was conducted to address methodological heterogeneity across these studies. Results: LLM applications were concentrated in constrained information-extraction and classification tasks, including signal evaluation, clinical-note extraction, social media surveillance, and literature screening. Quantitative performance varied substantially by system design: error-correction prompting yielded an F1-score of 0.921 for ADR named entity recognition, whereas retrieval-augmented generation improved data-retrieval accuracy from 8.3% to 78.3%. Most studies were retrospective, benchmark-based, or proof-of-concept evaluations. Across 581 paired pre-consensus domain judgements, observed inter-rater agreement was 90.4% and Cohen’s κ was 0.837 (95% CI 0.772–0.895). Hallucination, low specificity, prompt sensitivity, narrow datasets, and weak external validation remained common limitations. Conclusions: Current evidence supports supervised, task-specific applications of LLMs for extraction, triage, retrieval, and documentation rather than autonomous pharmacovigilance decision-making. Prospective evaluation, external validation, transparent reporting, and accountable human oversight are required before high-stakes clinical or regulatory deployment. Full article

Background/Objectives: Digoxin, a positive inotropic agent with a narrow therapeutic window, is used in heart failure but carries toxicity risks. This study aims to characterize the profile of digoxin-associated adverse drug reactions reported in the EudraVigilance database, focusing on drug–drug interactions, dosing errors, and off-label use. Methods: Descriptive and disproportionality analyses were performed on Individual Case Safety Reports (ICSRs) until 25 January 2026. Digoxin was compared with other inotropic agents by calculating the Reporting Odds Ratio and 95% confidence intervals. Results: Digoxin recorded 11,426 ICSRs, with a predominance in patients aged 65–85 years (46.4%) and over 85 years (25.1%). Higher reporting probabilities were identified for the terms “Drug interaction” and “Overdose” compared to other inotropes. Fatal outcomes were reported in 19 cases related to drug interactions and 41 cases related to overdose. Consistent disproportionality signals were found for gastrointestinal, renal, and nervous system disorders. Off-label use was reported in 0.8% of cases and was associated with unfavorable clinical outcomes. Risks are exacerbated by polypharmacy and renal decline in elderly patients. Conclusions: Digoxin toxicity and cardiac complications are the primary drivers of reported morbidity. This risk profile highlights the need for the rigorous clinical monitoring, precise dose adjustments and heightened vigilance regarding drug–drug interactions. Full article

Background/Objective: Polypharmacy, conventionally defined as the concurrent use of five or more medications, has emerged as a critical public health challenge in aging populations worldwide. Polypharmacy in older adults, driven by multimorbidity and age-related physiological changes, increases the risk of adverse drug reactions, drug interactions, falls, cognitive impairment, non-adherence, and preventable hospitalization. This study aims to provide a structured narrative synthesis of the current evidence on the incidence, risk factors, and clinical management of polypharmacy in elderly patients, with particular emphasis on deprescribing strategies, interdisciplinary care models, patient education, and digital clinical decision support technologies. Methods: A structured narrative literature review was conducted across PubMed, Scopus, and Web of Science using Boolean combinations of MeSH and free text terms including ‘polypharmacy,’ ‘elderly,’ ‘deprescribing,’ and ‘medication review.’ Eligible sources were peer-reviewed primary studies published between January 2016 and June 2026 that enrolled adults aged ≥65 years and reported validated prescribing review approaches, such as the STOPP/START criteria. The review drew on 40 primary studies spanning randomized controlled trials (RCTs) and observational, qualitative, and mixed-methods designs, which were interpreted and synthesized narratively across the principal thematic domains of polypharmacy management. Results: Polypharmacy was independently and consistently associated with DDIs, preventable hospitalizations, and functional decline across diverse clinical settings. Pharmacist-led medication reviews and interdisciplinary, team-based interventions produced the most robust improvements in prescribing appropriateness and meaningful reductions in potentially inappropriate medications (PIMs). Electronic clinical decision support systems (CDSSs) have demonstrated measurable benefits for safe deprescribing at scale, although usability limitations, incomplete workflow integration, and clinician resistance are significant implementation obstacles. Conclusions: Effective management of polypharmacy in older adults requires a multicomponent, patient-centered strategy that integrates evidence-based deprescribing algorithms, principally the STOPP/START criteria, sustained interdisciplinary collaboration, structured patient education, and technology-assisted decision support. Full article

Background/Objectives: The global rise in obesity-related hypertension, metabolic syndrome, and chronic inflammation calls for a precise characterization of the safety profiles of first-line therapies. While amlodipine is considered metabolically neutral, its real-world impact on dysglycemia and inflammatory biomarkers remains incompletely defined. This study aims to characterize the metabolic and inflammatory adverse drug reaction profile of amlodipine, using the EudraVigilance database. Methods: Descriptive and disproportionality analyses were performed on 41,872 Individual Case Safety Reports recorded prior to 17 May 2026. Amlodipine was compared against major antihypertensive classes (beta-blockers, angiotensin-converting enzyme (ACE) inhibitors, sartans, and diuretics), calculating reporting odds ratios (ROR) and 95% confidence intervals. Results: “Hyperglycaemia” could be considered a safety signal for amlodipine, compared to beta-blockers (e.g., bisoprolol—ROR: 2.56), ACE inhibitors (e.g., ramipril—ROR: 2.82), and sartans (e.g., candesartan—ROR: 3.85). “Metabolic syndrome” was reported for amlodipine with a lower probability than for hydrochlorothiazide (ROR: 0.35). Inflammatory signals (e.g., increased C-reactive protein) appeared less frequently for amlodipine than for certain renin–angiotensin–aldosterone system inhibitors (e.g., perindopril—ROR: 0.53). Conclusions: The disproportionality analysis identified relatively lower reporting frequencies for several metabolic and inflammatory adverse drug reactions, compared with selected antihypertensive agents. These findings represent pharmacovigilance signals that warrant further investigation in analytical epidemiological and clinical studies. Although hyperglycemia was reported disproportionally relative to several comparator drugs, reports of T2DM were less frequently reported for amlodipine. However, these observations should not be interpreted as evidence of differences in clinical risk, because disproportionality analyses cannot establish incidence or causality. Reports of inflammation likely reflect patient comorbidities rather than a direct drug effect. These findings demonstrate that post-marketing surveillance remains essential, even when accounting for the methodological limitations of spontaneous reporting. Full article

Background: Gabapentinoids (gabapentin and pregabalin) are medications used to treat epilepsy and diabetic neuropathy. Reports of gabapentinoid-associated adverse drug reactions (ADRs) are increasing. This study aimed to explore these potential signals, with a focus on ocular adverse effects. Methods: A mixed-methods design was adopted, utilising quantitative and qualitative approaches encompassing: (I) a social listening approach using Reddit; (II) a pharmacovigilance retrospective disproportionality analysis study using serious reports to the FDA Adverse Event Reporting System (FAERS) (2015–2025); and (III) a literature review (2014–2025). Results: Reddit data revealed several user-reported adverse ocular effects, including blurred vision, diplopia and photosensitivity, across 78 and 40 identified reactions for gabapentin and pregabalin, respectively. Pharmacovigilance findings identified positive signals for eye disorders with both gabapentinoids compared to active control diazepam, amitriptyline and carbamazepine). Incidental findings highlighted potential discrepancies between FAERS data and undesired effects listed within the manufacturer’s literature, with pregabalin exhibiting higher reporting odds than gabapentin for cataract (ROR: 4.55; 95% CI: 2.51–8.26) and blindness (ROR: 2.63; 95% CI: 1.85–3.73). The literature review reinforced eye disorder concerns, specifically retinal effects with gabapentinoids, noting the absence of robust, high-quality research. Nevertheless, it identified a plausible biological mechanism involving the CACNA2D1 receptor in retinal cells of animal models, with evidence of an effect following oral administration of pregabalin. Conclusions: This study suggests an increase in eye disorder reports associated with gabapentinoid use. Further clinical and epidemiological studies are warranted to validate these real-world signals. Full article

Toxic epidermal necrolysis (TEN) is a rare, life-threatening mucocutaneous adverse drug reaction associated with extensive epidermal necrosis and severe systemic complications. We report the case of a 25-year-old woman who developed severe lamotrigine-induced TEN four weeks after treatment initiation. The disease rapidly progressed to involve approximately 60% of the body surface area, requiring intensive care unit admission, mechanical ventilation, and multidisciplinary management. Treatment included high-dose intravenous methylprednisolone, intravenous immunoglobulins, etanercept, plasmapheresis, and comprehensive supportive care. During hospitalization, the patient developed gastrointestinal complications manifested by pneumatosis intestinalis and portal venous gas, raising suspicion of bowel ischemia and prompting exploratory laparotomy. Following treatment, gradual clinical improvement and complete resolution of the cutaneous lesions were achieved. However, persistent ocular sequelae developed, including meibomian gland dysfunction, punctate epithelial erosions, conjunctival scarring, trichiasis, tear film instability, and early corneal neovascularization, requiring long-term ophthalmological follow-up. To provide clinical context, a narrative review of the literature on the diagnosis, multidisciplinary management, gastrointestinal manifestations, ocular complications, and systemic treatment of TEN was performed. A comprehensive literature search was conducted to identify relevant articles focusing on the intensive care management and specific organ-related manifestations of Toxic Epidermal Necrolysis (TEN). The gathered literature was narratively synthesized to present a cohesive update on current clinical practices and management controversies. This case highlights the potentially devastating multiorgan course of TEN and emphasizes the importance of early recognition, specialized intensive care, and long-term multidisciplinary follow-up. Full article

Background: Atopic dermatitis (AD) and asthma are common type 2 inflammatory diseases linked by the atopic march. In adults with AD, the prevalence of comorbid asthma and the strength of the AD–asthma association remain uncertain, with marked heterogeneity across studies. Moreover, the role of modern systemic therapies in this comorbidity is increasingly debated. Objective: To estimate the global pooled prevalence of asthma in adults with AD, quantify the AD–asthma association, and discuss the potential impact of targeted therapies (dupilumab, abrocitinib, omalizumab) on asthma comorbidity. Methods: Systematic review and random-effects meta-analysis (ID CRD420261304804) of observational studies from PubMed, EMBASE, and Cochrane Library (inception to 19 January 2026). Pooled prevalence and odds ratios (ORs) were calculated, with subgroup analyses by region, ethnicity, and disease definition. Results: Seventy-five studies were included. The global pooled prevalence of asthma in adults with AD was 25.9% (95% CI 22.1–30.0%; I² = 99.9%). AD was significantly associated with asthma (OR 3.64, 95% CI 2.89–4.57; I² = 98.6%). Prevalence varied from 9.3% in Asia to 63.2% in South America. Although dupilumab and other targeted agents are effective in both diseases, isolated reports of new-onset asthma after treatment were identified; these cases more likely reflect the natural progression of AD or unmasking of pre-existing asthma than a direct adverse drug reaction. Conclusions: Asthma is highly prevalent in adults with AD and is strongly associated with AD. Geographic and ethnic disparities call for stratified screening. Clinicians should be aware that new-onset respiratory symptoms during targeted therapy may represent AD-related comorbidity rather than drug-induced asthma. Full article

Gastrointestinal (GI) adverse drug reactions (ADRs) are common among glucagon-like peptide-1 receptor agonist (GLP-1 RA) users and frequently contribute to treatment discontinuation and reduced therapeutic benefit. This retrospective study aimed to develop and validate an explainable artificial intelligence (XAI) model to predict GI ADR risk among GLP-1 RA users using real-world clinical data from the NIH All of Us Research Program. Adults prescribed GLP-1 RAs were identified and classified according to the occurrence of GI ADRs following treatment initiation. Multiple supervised machine learning models, including logistic regression, random forest, extreme gradient boosting (XGBoost), support vector machine, neural network, LightGBM, and CatBoost, were evaluated using demographic, socioeconomic, clinical, medication, and laboratory variables. Model performance was assessed using area under the receiver operating characteristic curve (AUC), accuracy, precision, recall, and F1-score. A total of 8697 participants were included, of whom 59.1% experienced GI ADRs. All models demonstrated reasonable predictive performance, with AUC values ranging from 0.82 to 0.84. The XGBoost achieved discrimination of (AUC: 0.84 ± 0.01). SHapley Additive exPlanations (SHAP) identified gastroesophageal reflux disease, hemorrhoids, and elevated HbA1c as important predictors of GI ADR risk. These findings demonstrate the potential utility of explainable machine learning approaches for predicting the safety of GLP-1 RA therapy. Full article

Background: Hepatotoxicity induced by atomoxetine (ATX) and methylphenidate (MPH) when used to treat ADHD is a rare but potentially serious complication. This study aims to describe the hepatic adverse drug reactions (ADRs) reported for ATX and MPH by analysing data from the EudraVigilance database. Methods: Individual case safety reports (ICSRs) listing ATX and/or MPH as suspected drugs and reporting at least one adverse event (AE) within the ‘hepatobiliary disorders’ system organ class (SOC) were extracted for the period from 1 January 2012 to 20 May 2025. Descriptive and disproportionality analyses were then performed. Results: During the study period, 421 ICSRs reporting AEs classified under the “hepatobiliary disorders” SOC and involving ATX and/or MPH as suspected drugs were retrieved (ATX, N = 232; MPH, N = 181). Most cases involved adult (N = 261) and female (N = 222) patients. The majority of reports were classified as serious (N = 349). Overall, 375 AEs were identified. Drug-induced liver injury (DILI) was the most frequently reported AE (N = 103 ATX; N = 47 MPH), followed by hepatitis (N = 20 ATX; N = 9 MPH) and jaundice (N = 15 ATX; N = 20 MPH). The disproportionality analysis, based on a head-to-head comparison, showed a higher reporting frequency of hepatobiliary disorders for ATX compared to MPH (ROR 2.41 [95%CI 2.11–3.11]). Specifically, ATX was associated with significantly higher reporting frequencies than MPH for the AEs of DILI, hepatitis, and jaundice (6.42 [4.45–9.06]; 6.48 [2.95–14.24]; and 2.19 [1.12–4.27], respectively). Conclusions: This analysis, based on the EudraVigilance database, suggests that both drugs are associated with hepatobiliary adverse drug reactions, with a higher overall reporting frequency observed for ATX. Full article

Background/Objectives: Previous studies have demonstrated the safety of pre-seasonal treatment with the mannan-conjugated birch pollen allergoid EP-088-T502. However, the safety of a combined pre- and co-seasonal treatment regimen has not yet been investigated. As climate change is associated with earlier and less predictable onset of birch pollen seasons, planned pre-seasonal allergen immunotherapy may unintentionally overlap with natural pollen exposure. Therefore, evaluation of the safety of treatment administered during the pollen season is of increasing clinical relevance. This study aimed to compare, in a purely descriptive manner, the safety and tolerability of pre-seasonal versus pre- and co-seasonal treatment with EP-088-T502. Methods: In this prospective, open-label, phase III trial (T502-SIT-059) (EudraCT No.: 2022-004082-20), patients (N = 109) who had participated in a preceding pivotal phase III study were offered continuation treatment with active EP-088-T502 (10,000 mTU/mL) across five treatment visits. For the subgroup analysis, all patients who completed their last treatment visit before 9 April 2023 (and, thus, before the start of the birch pollen season in Germany) were assigned to the pre-seasonal group (N = 20). Those who performed the last treatment visit thereafter were assigned to the pre-/co-seasonal group (N = 83). Due to post hoc subgroup allocation and unequal subgroup sizes, all subgroup analyses were purely descriptive. Results: No deaths nor serious adverse events (SAEs) were reported during the study. No epinephrine administration was required. Systemic adverse drug reactions (SADRs, N = 3) occurred in two patients who had previously received placebo. No grade III or IV systemic reactions, according to the German AWMF classification, were observed. Patients receiving pre- and co-seasonal treatment developed smaller wheals (mean diameter) compared with the pre-seasonal group (immediate reactions: 0.6 vs. 0.7 cm; late-phase reactions: 0.3 vs. 0.4 cm at the last treatment visit). This was also reflected in the medians (immediate reactions: 0.2 cm vs. 0.4 cm; late-phase reactions: 0.2 vs. 0 cm at the last treatment visit). Of all AEs that were (possibly) related to EP-088-T502 (N = 89), 74 (83%) occurred at the first three treatment visits (before the birch pollen season). The frequency of AEs appeared descriptively similar between groups for the last two treatment visits. Patients who had received placebo in the previous trial experienced more treatment-related side effects compared to patients who had already received EP-088-T502 in the previous year. Conclusions: These data suggest that EP-088-T502 is safe and well-tolerated, even when administered during the birch pollen season, regardless of prior exposure to EP-088-T502. Full article

Background: Mirikizumab, a first-in-class interleukin-23p19 antagonist, was approved for ulcerative colitis (2023) and Crohn’s disease (2025). The US Food and Drug Administration (FDA) identified a hepatotoxicity signal during pre-approval review, mandating post-marketing surveillance. No independent pharmacovigilance analysis has been published. Aims: To characterise the post-marketing safety profile of mirikizumab using multi-database pharmacovigilance, with a focus on hepatotoxicity and IL-23 inhibitor class comparison. Methods: Disproportionality analysis of the FDA Adverse Event Reporting System (FAERS; Q4 2023–Q4 2025) and Japanese Adverse Drug Event Report database (JADER) was performed using four algorithms (reporting odds ratio, proportional reporting ratio, Bayesian confidence propagation neural network, empirical Bayesian geometric mean). Signals of disproportionate reporting were defined by concordance of all four methods. Active comparator analysis against risankizumab, guselkumab and ustekinumab, Weibull time-to-onset modelling and hepatotoxicity case characterisation were conducted. Reporting followed READUS-PV guidelines. Results: We identified 564 mirikizumab reports in FAERS and 123 in JADER. Nine signals met all four criteria in FAERS, including spontaneous abortion (Reporting odds ratio (ROR) 10.16, 95% CI 5.16–20.02), pulmonary embolism (ROR 5.56, 2.93–10.56) and injection site reactions. Hepatotoxicity showed no disproportionate reporting in either FAERS (ROR 1.19, 0.74–1.92; n = 17) or JADER (ROR 0.24, 0.05–1.19; n = 1). Comparator analysis identified cytomegalovirus infection and interstitial lung disease as mirikizumab-specific versus the IL-23 class. Weibull analysis (β = 0.65) indicated early-onset adverse event clustering. Discussion: This first multi-database pharmacovigilance study of mirikizumab did not confirm the FDA-flagged hepatotoxicity signal. Potential signals warranting further investigation include thromboembolic events and pulmonary toxicity. Full article