Search Results (2,000)

Background: A significant proportion of individuals with Takayasu arteritis (TA) experience relapses notwithstanding standard treatment with glucocorticoids, and conventional synthetic or biologic disease-modifying antirheumatic drugs (DMARDs). As the Janus kinase/signal transducer and activator of transcription (JAK/STAT) signaling pathway contributes to the pathogenesis of TA, JAK inhibitors (JAKi) could represent a viable therapeutic alternative. This study assessed the effectiveness of JAKi in patients with relapsing TA within a real-world setting in a country with a low incidence of TA such as Spain and included a comprehensive review of the literature. Methods: we conducted a retrospective analysis of TA patients managed with JAKi for recurrent disease across three Spanish centers. Evaluated outcomes comprised clinical remission, clinical and analytical remission, glucocorticoid-sparing effect, improvement in imaging techniques, and adverse events. A systematic literature search was performed to identify further cases of TA treated with JAKi. Results: six patients (83.3% females) with a mean age 48.5 years and relapsing TA received JAKi therapy: baricitinib (n = 2); tofacitinib (n = 2), and upadacitinib (n = 2). Before JAKi therapy, all (100%) patients had received conventional synthetic immunosuppressants, and four (66.7%) biologics. Clinical remission was achieved in 2/6 (33.3%), 3/5 (60%), 3/5 (60%), 2/3 (66.7%), and 2/2 (100%) patients at 1, 3, 6, 12 and 18 months, respectively. Clinical + analytical remission was observed in 1/6 (16.7%), 2/5 (40%), 2/5 (40%), 2/3 (66.7%), and 2/2 (100%) patients, respectively. Two patients who underwent a follow-up PET/CT imaging showed partial improvement in both. After a median (IQR) follow-up of 9.5 (6.0–16.7) months, one (16.7%) patient discontinued the initial JAKi due to no improvement and one patient discontinued it because was diagnosed with tonsillar neoplasia. The literature search identified another 166 JAKi-treated TA cases with clinical improvement reported for the majority of them. Conclusions: this real-world analysis and literature review suggest that JAKi could be effective in the management of TA, including for those patients who have failed established glucocorticoid-sparing strategies. Full article

Introduction: Teprotumumab (Tepezza^®), an insulin-like growth factor-1 receptor (IGF-1R) antagonist, is the first FDA-approved targeted therapy for thyroid eye disease (TED). While effective for reducing proptosis and inflammation, increasing post-marketing evidence has linked teprotumumab to auditory adverse events. IGF-1 signaling is essential for cochlear maintenance and neuroprotection; therefore, systemic IGF-1R inhibition presents a biologically plausible mechanism for ototoxicity. Despite growing recognition of these effects, no standardized approach exists for audiologic assessment or monitoring of patients receiving teprotumumab. This review aimed to (1) summarize proposed mechanisms and the reported spectrum of teprotumumab-related auditory effects, (2) evaluate current methods used to assess and monitor these patients, and (3) identify areas of consensus and ongoing uncertainty. Methods: An updated narrative review of the literature was conducting using PubMed, CINAHL, and Google Scholar using Boolean strings targeting teprotumumab exposure and hearing-related outcomes. Studies from 2022 onward were identified using Boolean search strings targeting teprotumumab exposure and hearing-related outcomes. Peer-reviewed English language studies reporting audiometric findings were eligible for inclusion. Results: Ten studies met inclusion criteria. Reported effects most commonly included bilateral high-frequency SNHL, tinnitus, and aural fullness, typically emerging after three to six infusions. Many cases demonstrated persistent deficits despite drug discontinuation. Baseline audiometric assessment was not uniformly reported across studies, and monitoring protocols varied considerably, with inconsistent incorporation of speech testing and immittance measures. Conclusions: Teprotumumab-associated ototoxicity is increasingly recognized and potentially irreversible. Current evidence is insufficient to guide standardized monitoring. Prospective studies are urgently needed to establish evidence-based audiologic surveillance protocols. Full article

Background: As glucagon-like peptide-1 (GLP-1) receptor agonist use expands globally, reports of psychiatric adverse events (AEs) have increased in spontaneous reporting databases. However, which case-level characteristics are associated with these reporting patterns remains insufficiently characterized. This study aimed to characterize case-level features associated with psychiatric AE reporting in GLP-1 receptor agonist users through pharmacovigilance and explainable machine learning methods. Methods: The FDA Adverse Event Reporting System (FAERS) data (2021 Q2–2025 Q3) were analyzed using a comparator-based approach comprising other antidiabetic and anti-obesity agents. Disproportionality analyses (PRR, ROR, and IC) were performed to detect consolidated safety signals at the Preferred Term (PT) level, with additional drug-specific analyses for individual GLP-1 receptor agonists. Three classification models (logistic regression, XGBoost, and LightGBM) were developed, and SHAP values were used to identify case-level features associated with psychiatric AE reporting patterns. Results: A total of 211,195 unique cases were included (111,105 for GLP-1 receptor agonists; 100,090 for comparators). Sixteen PTs met consolidated signal criteria, with suicidal ideation being the most frequently reported (ROR 2.95). Drug-specific analyses indicated that signal magnitudes were consistently higher for semaglutide than tirzepatide. The XGBoost model achieved an AUROC of 0.816. SHAP analysis showed that age ≥65 years had the highest mean |SHAP| value (0.57) with a negative direction, corresponding to a lower predicted probability of psychiatric AE reporting in older adults. Semaglutide use ranked second (0.35) and showed a positive direction. Absence of concomitant medications (0.20) and diabetes indication (0.10) showed negative directions, while younger age (19–44 years, 0.08) showed a positive direction. These patterns remained consistent in sensitivity analysis excluding concomitant psychotropic medication users (AUROC 0.797). Conclusions: Older age status was associated with decreased predicted probability of psychiatric AE reporting, while semaglutide use and younger age showed positive contributions. These case-level patterns, identified through pharmacovigilance analysis using a comparator-based approach and explainable machine learning, suggest that reporting patterns may differ across subgroups and that the observed reporting heterogeneity among younger adults and semaglutide users merits further investigation in prospective studies. Full article

Background/Objectives: Inflammatory bowel disease (IBD) represents a growing therapeutic challenge, and the identification of novel treatment strategies remains an unmet clinical need. Drug repurposing offers a pragmatic and cost-effective alternative to de novo drug development. This study aimed to identify candidate drugs for repurposing in IBD through inverse signal detection within a large spontaneous pharmacovigilance database. Methods: In this observational, retrospective pharmacovigilance study, data from the FDA Adverse Event Reporting System (FAERS) were analyzed using OpenVigil 2.1. Drugs inversely associated with IBD were identified based on a ROR < 1 and an adjusted p-value < 0.05. Candidates were subsequently filtered to exclude agents with implausible indications, unfavorable pharmacokinetic profiles, or recognized contraindications to use in IBD. Although this screening process yielded a broader set of repurposing candidates across multiple drug classes, the present study focused specifically on antidiabetic medications, which were subjected to a targeted literature review evaluating their immunomodulatory properties, anti-inflammatory mechanisms, and existing preclinical and clinical evidence in the context of IBD. Results: Of 3585 initial drug–event combinations evaluated, 73 candidates met predefined criteria for statistical significance, pharmacokinetic feasibility, and clinical relevance. Within this broader pool, ten antidiabetic agents which demonstrated meaningful inverse signal strength were selected for in-depth analysis: dulaglutide (ROR 0.181, 95% CI 0.136–0.242), insulin lispro (ROR 0.206, 95% CI 0.161–0.263), insulin glargine (ROR 0.246, 95% CI 0.205–0.295), insulin (ROR 0.340, 95% CI 0.295–0.390), insulin aspart (ROR 0.349, 95% CI 0.267–0.455), empagliflozin (ROR 0.400, 95% CI 0.311–0.514), liraglutide (ROR 0.419, 95% CI 0.319–0.552), metformin (ROR 0.446, 95% CI 0.407–0.489), sitagliptin (ROR 0.460, 95% CI 0.376–0.563), and semaglutide (ROR 0.622, 95% CI 0.507–0.764). The subsequent literature review discussed relevant immunomodulatory and anti-inflammatory properties for each of these agents, providing a mechanistic rationale for their potential therapeutic role in IBD. Conclusion: This study identifies antidiabetic drugs as plausible repurposing candidates for IBD, supported by both pharmacovigilance-derived inverse signals and a body of mechanistic and clinical literature suggesting shared pathophysiological pathways between the two conditions. However, it should be acknowledged that the clinical evidence supporting the therapeutic efficacy of several candidates remains variable or incomplete, and robust interventional data are largely lacking. Ultimately, the findings of this study generate testable hypotheses and highlight a set of candidate therapies that warrant dedicated experimental and clinical investigation, including well-designed prospective trials, to determine their true therapeutic potential in IBD management. Full article

Background: Alcohol use disorder (AUD) is a grave mental health condition that can result in significant health and social consequences. The medications Naltrexone and Nalmefene are indicated for the treatment of AUD, with Naltrexone having received the most extensive research attention. Methods: The majority of papers assessing universal measures of alcohol consumption employed two primary metrics: total alcohol consumption (TAC) and the number of days per month where individuals engaged in heavy drinking (HDD). Indicators pertaining to the maintenance of complete abstinence were excluded due to the absence of sufficient data. The safety of both substances was also assessed, as were the frequency of side effects and independent patient dropout. The study also incorporated practical factors of the therapy, such as the route of administration, dosage regimen, and the drug’s patient convenience, which can have a significant impact on adherence to therapy. Results: Nalmefene, administered in an “as needed” regimen, demonstrated statistically significant activity in reducing HDD and total alcohol consumption (TAC) among patients with AUD, particularly those with elevated World Health Organization (WHO) DRL risk. Preliminary findings from the ESENSE1 (Efficacy of Nalmefene in Alcohol Dependence; the first phase III study), ESENSE 2 (Efficacy of Nalmefene in Alcohol Dependence, the second phase III study), and SENSE (the final phase III long term-safety and cost-effectiveness study) studies indicate a substantial decrease in HDD and TAC following the initial month of treatment. These effects persist throughout the subsequent follow-up period. Several Japanese studies have corroborated the effectiveness of Nalmefene, demonstrating its efficacy across both short-term and long-term applications. Furthermore, these studies have substantiated its safety profile, indicating that there is no inherent risk of addiction or the emergence of withdrawal symptoms. The mild nature of adverse events (most commonly nausea and dizziness) led to a relatively low discontinuation rate of Nalmefene treatment. A subsequent study, employing a recognized methodology, corroborated the efficacy of psychosocial support in enhancing treatment outcomes. Meta-analyses demonstrate that Naltrexone exhibits comparable efficacy in reducing the frequency and severity of alcohol consumption. In select populations, the injectable form (LAI) of this pharmaceutical agent facilitates less frequent dosing, which is advantageous for the treatment process. A comparison of Nalmefene and Naltrexone reveals that the latter does not demonstrate a significant impact on the likelihood of individuals returning to heavy alcohol consumption. Conclusions: In the treatment of AUD, both naltrexone and nalmefene have been shown to yield positive outcomes, particularly in terms of reducing the HDD and TAC. According to the World Health Organization (WHO) classification, Nalmefene is indicated for individuals with a high risk of developing serious conditions. It has been demonstrated to produce rapid and sustained results while exhibiting a favorable safety profile, characterized by the absence of significant adverse effects. Naltrexone is a medication that has proven to be effective. LAI may have a positive impact on the efficacy of treatment. Full article

Fibroblast growth factor receptor 2 (FGFR2) inhibitors such as pemigatinib are targeted therapies for cholangiocarcinoma with FGFR2 alterations. While generally well tolerated, they are associated with unique adverse events. Calciphylaxis, a potentially fatal vascular calcification disorder, is a rare complication. We present a 43-year-old woman with metastatic intrahepatic cholangiocarcinoma harboring an FGFR2 fusion who developed calciphylaxis after seven months of pemigatinib therapy. Despite drug discontinuation, antibiotics, and multidisciplinary supportive care, she deteriorated rapidly and died from sepsis and advanced disease. Histopathological analysis confirmed dermal and vascular calcifications consistent with calciphylaxis. This case highlights the importance of early recognition of cutaneous lesions in patients on FGFR inhibitors. Prompt cessation of therapy, management of metabolic derangements, and consideration of sodium thiosulfate may be lifesaving. Full article

Background/Objectives: The recent approval of the first intranasal calcitonin gene-related peptide receptor antagonist (CGRP-RA), zavegepant, has increased the relevance of this drug class in treating acute migraine. However, introducing an alternative delivery method may result in a different real-world safety profile. Thus, the aim of this study was to assess adverse events (AEs) related to zavegepant through a retrospective pharmacovigilance disproportionality analysis. Methods: We analyzed Individual Case Safety Reports (ICSRs) presenting zavegepant as the suspected drug, submitted to the Food and Drug Administration (FDA) Adverse Event Monitoring System (AEMS) database between 1 January 2023 and 31 December 2025. ICSRs were assessed by using descriptive and disproportionality analyses. Reporting odds ratios (RORs) with 95% confidence intervals (CIs) were used as disproportionality measures. Results were deemed significant if the ROR 95% CI lower bound was >1 and ≥3 ICSRs were available for each drug–event pair. Results: A total of 509 zavegepant-related ICSRs were identified. Most ICSRs involved female patients (n = 353; 69.4%), with a median (quartile 1, Q1–quartile 3, Q3) age of 45 (34–56) years. The Medical Dictionary for Regulatory Activities (MedDRA^®) Preferred Terms with the highest RORs were nasal discomfort (n = 62; ROR = 298.85; 95%CI [228.91, 390.17]), rhinalgia (10; 126.09; [67.34, 236.09]), dysgeusia (147; 94.72; [78.19, 114.75]), pharyngeal ulceration (3; 79.20; [25.42, 246.75]), and upper-airway cough syndrome (16; 62.87; [38.19, 103.49]). Conclusions: These results suggest a safety profile for zavegepant consistent with previous knowledge regarding CGRP-RAs. However, nasal and/or oropharyngeal AEs, plausibly related to intranasal exposure, may affect perceived tolerability and timely use, warranting further investigation. Full article

Background/Objectives: Rifampicin-resistant tuberculosis (RR-TB) and HIV co-infection remain major contributors to morbidity and mortality, particularly in high-burden settings. HIV-related clinical factors, including viral suppression, CD4-defined immune status, HIV drug resistance, virological failure, and ART failure, may influence RR-TB treatment response; however, existing evidence remains fragmented. This systematic review and meta-analysis protocol aims to synthesize evidence on the impact of HIV viral suppression, immune status, and HIV drug resistance/ART resistance status on RR-TB treatment outcomes. Methods: This protocol was developed in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses Protocols guidelines. Published peer-reviewed studies and relevant grey literature from January 2005 to December 2025 will be searched in PubMed/MEDLINE, Cochrane Library, Embase, Web of Science, ScienceDirect, EBSCOhost, PsycINFO, Google Scholar, and other relevant sources. No language restriction will be applied at the search stage. Where feasible, non-English records will be translated for title/abstract and full-text screening. Two reviewers will independently screen studies, extract data, and assess study quality, with disagreements resolved by a third reviewer. Study-level risk of bias will be assessed using design-appropriate tools, and the certainty of evidence for each outcome will be evaluated using GRADE. Results: Evidence will be synthesized narratively and, where studies are sufficiently homogeneous, quantitatively through meta-analysis. Outcomes of interest will include treatment success, treatment failure, mortality, treatment completion, microbiological cure, and adverse events. Subgroup analyses will be considered by viral suppression status, CD4-defined immune status, HIV drug resistance/ART resistance status, geographic region, and treatment regimen where data permit. Conclusions: This review will provide evidence on how HIV viral suppression, immune status, and HIV drug resistance/ART resistance influence RR-TB treatment outcomes. The findings may inform integrated TB/HIV care, clinical monitoring, and treatment strategies for individuals co-infected with HIV and RR-TB. Full article

Background and Objectives: Muscle symptoms are the most visible adverse event attributed to statins, but terminology is often imprecise. Most patients report myalgia or nonspecific aches, whereas objective myopathy, inflammatory or necrotizing myositis, rhabdomyolysis, and anti-HMGCR immune-mediated necrotizing myopathy are uncommon and clinically distinct entities. To provide a clinically oriented narrative synthesis of statin-associated muscle symptoms (SAMS) and severe statin-associated myotoxicity, and to propose a practical prevention, evaluation, and management algorithm. The classification of muscle events is used to standardize terminology and avoid diagnostic confusion, not to create a new formal taxonomy. Materials and Methods: A clinically oriented narrative review was performed using PubMed, Google Scholar, and major society documents published from January 2021 to April 2026. Eligible sources addressed SAMS, statin myopathy/myositis, rhabdomyolysis, anti-HMGCR immune-mediated necrotizing myopathy, nocebo/drucebo effects, pharmacogenetics, drug interactions, diagnosis, or management. The final evidence set comprised 55 verifiable sources, including blinded randomized or n-of-1/crossover evidence; meta-analyses; clinical statements and reviews; pharmacovigilance analyses; pharmacogenetic guidance; mechanism-focused reviews; anti-HMGCR series; and lipid-lowering guideline/treatment studies. Because the review was narrative, no pooled estimate or formal PRISMA screening log was generated. Results: Blinded evidence indicates only a small absolute excess of muscle pain with statins, concentrated mainly in the first year of therapy, and that most muscle symptoms reported during statin therapy are not pharmacologically caused by the statin. N-of-1 and crossover trials show that symptom intensity is often similar during statin and placebo periods, consistent with an important nocebo/drucebo contribution. Severe muscle toxicity can nevertheless occur, especially when systemic statin exposure is increased by a high dose, interacting drugs, frailty, renal or hepatic impairment, hypothyroidism, transporter or metabolic genotypes, or intense unaccustomed exercise. Statin choice matters chiefly through dose, pharmacokinetics, and interaction burden. Conclusions: SAMS are common as reported clinical problems, but confirmed statin-caused muscle injury is substantially less frequent than routine clinical attribution suggests. Permanent discontinuation should be reserved for carefully assessed cases. A structured approach—baseline risk assessment, selective CK measurement, exclusion of alternative causes, correction of modifiable risks, dechallenge/rechallenge, statin switching, dose reduction, and combination with non-statin therapy—preserves cardiovascular benefit while protecting the rare patient with genuine toxicity. Full article

Approximately 10% of the general population reports a penicillin allergy, making it one of the most commonly documented drug allergies in clinical practice. Yet formal evaluation confirms true hypersensitivity in fewer than 10% of these cases. This gap has practical consequences. Patients who carry an inaccurate allergy label are more likely to receive broader-spectrum alternative antibiotics, with downstream effects on cost, adverse drug events, and antimicrobial resistance. Although primary care physicians are often the first to record these labels and the ones who face their consequences most often in daily prescribing, they have remained peripheral to most systematic delabeling efforts. In this narrative review, we examine how antibiotic allergy labels arise, why they persist, and what they cost—clinically, economically, and from a stewardship perspective. We also discuss emerging approaches to reassessment in primary care, including risk stratification tools and international guideline recommendations, along with the possible role of digital health tools and patient education in improving the accuracy of allergy documentation. Full article

Background: Cenobamate is a novel antiseizure medication with potential interactions involving cytochrome P450 enzymes, including CYP2C19. Genetic variability in CYP2C19 may influence drug metabolism and tolerability, although its clinical relevance in cenobamate-treated patients remains unclear. Methods: We conducted a single-center retrospective study including 48 adults with drug-resistant epilepsy treated with cenobamate. Patients were stratified by concomitant use of CYP2C19-substrate ASMs (patients with CYP2C19 substrates vs. patients without CYP2C19 substrates). CYP2C19 genotype was classified into metabolizer phenotypes. Adverse events (AEs) were categorized as potentially CYP-mediated or likely unrelated to CYP-mediated pharmacokinetic mechanisms based on clinical assessment, temporal association, and known pharmacological interaction profiles. Associations were explored using descriptive statistics and regression models. Results: Overall, 58.3% of patients received CYP2C19-substrate ASMs. AEs were more frequent among patients with CYP2C19 substrates (71.4% vs. 20.0%; p = 0.001), with potentially CYP-mediated AEs observed only in this group (32.1% vs. 0%; p < 0.001). Intermediate metabolizers showed a higher proportion of potentially CYP-mediated AEs (87.5%; p < 0.001). This pattern was not observed in patients without CYP2C19 substrates. Regression analyses suggested increased risk in intermediate metabolizers, although estimates were imprecise and should be considered exploratory. Conclusions: An exploratory association between CYP2C19 variability and AE occurrence was observed in patients treated with cenobamate combined mainly with clobazam and other CYP2C19-substrate ASMs. Intermediate metabolizers may represent a higher-risk subgroup, but these preliminary findings require prospective confirmation with pharmacokinetic monitoring. Full article

Background/Objectives: Medication discrepancies at hospital discharge are common and may contribute to adverse drug events and avoidable healthcare use. Patients with mental health conditions may be at increased risk because of greater clinical complexity, polypharmacy, and fragmented care, but comparative evidence during general hospital admissions is limited. Our primary objective was to determine whether adults with mental health conditions were more likely than those without such conditions to experience unintended medication discrepancies at hospital discharge. Secondary objectives were to examine discrepancy subtypes, assess whether associations differed for serious mental illness versus other mental health conditions, and explore whether associations varied by reconciliation arm. Methods: We conducted a retrospective cohort study using linked data from the RightRx cluster-randomized trial at the McGill University Health Centre (2014–2016) and Quebec administrative databases. Adults with continuous provincial drug coverage for at least 12 months before admission who met study eligibility criteria were included. The primary exposure was any documented mental health condition; secondary analyses distinguished serious mental illness (SMI) from other mental health conditions. The primary outcome was any unintended medication discrepancy at discharge; subtype analyses examined omissions, therapeutic duplications, and unintended dose changes. Results: Among 3567 patients, 877 (24.6%) had a mental health condition. Crude discrepancy prevalence was similar between groups. In the prespecified primary analysis, mental health condition status was associated with lower observed odds of any unintended discrepancy at discharge. This unexpected inverse association should not be interpreted as evidence of a protective effect and may reflect differences in documentation, residual confounding, selection, or other unmeasured processes. Secondary and supplementary analyses, including omission and SMI subgroup comparisons, did not remain statistically significant after Holm correction. Conclusions: These findings suggest that documentation-based discrepancy measures may relate to mental health status in heterogeneous ways, but they require confirmation in independent settings. Full article

Traditional drug discovery is a high-risk, time-consuming, and costly endeavor. Drug repurposing has emerged as a pivotal strategy to overcome these challenges by identifying new therapeutic indications for approved drugs, thereby significantly reducing development timelines, costs, and safety risks. This review aims to provide a comprehensive methodological survey of computational strategies for drug repurposing. It seeks to clarify the core principles, applicability, and limitations of various approaches, offering a clear technological landscape and valuable insights for future research directions. We categorize and elaborate on the prevailing methodologies, following a logical progression. The review begins with biological mechanism-driven methods, including structure-based, omics-based, fuzzy logic-based, and adverse event-based methods. It then details network-based methods that integrate multi-source data, encompassing graph mining and matrix factorization/completion techniques. Finally, we explore data-driven paradigms, tracing the evolution from traditional text mining-based methods to cutting-edge large language model (LLM)-based methods. Each methodological category presents unique advantages and challenges. While structure-based, omics-based, fuzzy logic-based, and adverse event-based methods provide deep mechanistic insights, network-based methods enable systematic prediction. Text mining unlocks information from vast literature, a potential greatly amplified by LLMs. This review highlights that the future of drug repurposing lies in the intelligent integration of diverse methodologies. In the future, we believe that network-based methods and data-driven methods will mark the beginning of large-scale drug repurposing, but ultimately, biological mechanism-driven methods will still be necessary for rigorous validation and explanation. Full article

This study addresses two key challenges in computational pharmacology: identifying novel therapeutic uses for existing drugs and modeling drug safety-related characteristics. We propose a multi-relational biomedical knowledge graph that integrates gene, drug, and disease associations with adverse effect data, enabling joint modeling of therapeutic and safety-related properties. A Relational Graph Convolutional Network (R-GCN) is employed to learn relationally aware embeddings that capture complex biological interactions across heterogeneous entities. The framework is evaluated on two tasks: (1) drug–disease link prediction for drug repurposing and (2) prediction of drug side-effect burden based on adverse event patterns. The experimental results demonstrate that the R-GCN model outperforms baseline methods, achieving 94.63% accuracy in drug–disease link prediction, while embedding-based classifiers attain up to 97.14% F1-score in side-effect burden classification. Additionally, multi-hop relational reasoning enables the discovery of biologically plausible connections between drugs, genes, and diseases. These findings highlight the effectiveness of knowledge graph-based representation learning in jointly supporting therapeutic discovery and safety-related analysis. While side-effect burden is used as a surrogate measure rather than a direct indicator of drug quality, the proposed framework provides a scalable foundation for integrating real-world pharmacovigilance and regulatory data in future studies. Full article

Background/Objectives: Ocrelizumab is a humanized monoclonal antibody targeting CD20, approved for the treatment of adult patients with relapsing multiple sclerosis (RMS) and primary progressive multiple sclerosis (PPMS). The neutralizing activity of anti-drug antibodies (ADAs), especially neutralizing ADAs (nADAs) activity, should be examined considering that it can alter pharmacokinetic (PK) and pharmacodynamic (PD) profiles, reduce drug efficacy, and lead to life-threatening adverse events. Methods: This article presents data on the development and validation of an assay for neutralizing anti-drug antibodies (nADA) based on ADCC reporter cells for the analysis of patient sera in the context of ocrelizumab clinical studies. Results: Critical steps and conditions to minimize assay variability were identified. The lower limit of detection was 549.6 ng/mL. The cutoff for nonspecific neutralization was determined as 19.7%. The presence of 0.37–3.0 μg/mL ocrelizumab in a biological sample enables the detection of 1.1–10.0 μg/mL polyclonal anti-ocrelizumab idiotype antibodies, respectively. Conclusions: The developed method can be used for immunogenicity studies of medicinal products containing ocrelizumab. Full article