Scavone C, Cagnotta C, Sportiello L
… +5 more, Maniscalco GT, Ragone A, Frasca M, Rinaldi B, Capuano A
Expert Opin Drug Saf
· 2025 Oct · PMID 41081871
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INTRODUCTION: Monoclonal antibodies (mAbs) targeting CD20 used in patients with multiple sclerosis (MS) can cause hypogammaglobulinemia, increasing the risk of infections. We aim to identify the proportion of individuals...INTRODUCTION: Monoclonal antibodies (mAbs) targeting CD20 used in patients with multiple sclerosis (MS) can cause hypogammaglobulinemia, increasing the risk of infections. We aim to identify the proportion of individuals developing these events during the treatment with an anti-CD20 mAb. METHODS: A systematic review of observational studies was conducted from 2014 to 2024. Studies involving patients with MS, receiving anti-CD20 mAbs, evaluating outcomes related to hypogammaglobulinemia and/or infections were included. A random effect meta-analysis approach was used. RESULTS: 55 articles were selected for meta-analysis, covering a population of 14,548 MS patients. Overall, rituximab exhibited a higher prevalence of hypogammaglobulinemia [11%; 95% Confidence Interval (CI): 0.08 to 0.15], infections of any grade (25%; 95%CI: 0.18 to 0.32), genito-urinary infections (9%;95%CI: 0.05 to 0.12), while ocrelizumab exhibited a higher prevalence of serious infections (6%; 95%CI: 0.03 to 0.09) and respiratory infections (12%; 95%CI: 0.07 to 0.17). The paucity of data for ofatumumab and ublituximab highlights a research gap. The proportion of these AEs increase with treatment duration. Substantial heterogeneity was identified in all analyses. The quality of included studies was mainly classified as poor. CONCLUSIONS: Monitoring and educating patients on anti-CD20 mAb is fundamental to quickly identifying adverse events and minimizing clinical risks. PROTOCOL REGISTRATION: www.crd.york.ac.uk/prospero identifier is CRD42024617575.
Expert Opin Drug Saf
· 2025 Oct · PMID 41074919
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BACKGROUND: Thrombolytic therapy is linked to angioedema, a serious adverse event, with higher risk when co-administered with renin-angiotensin-aldosterone system inhibitors (RAAS-i), particularly ACE inhibitors. However...BACKGROUND: Thrombolytic therapy is linked to angioedema, a serious adverse event, with higher risk when co-administered with renin-angiotensin-aldosterone system inhibitors (RAAS-i), particularly ACE inhibitors. However, this interaction remains incompletely characterized. RESEARCH DESIGN AND METHODS: A multi-modal analysis: (1) USFDA Adverse Event Reporting System (AERS) disproportionality analysis including reporting odds ratio (ROR); (2) case report review; and (3) meta-analysis and trial sequential analysis of observational studies was performed. Drug interactions were evaluated using multiplicative models. Primary outcomes were mortality and life-threatening events. RESULTS: Among 521 USFDA AERS reports, disproportionality signals were noted for alteplase (ROR: 3.1) and tenecteplase (ROR 2.85); and signal strength increased with RAAS-i co-administration. Mortality rates were comparable between thrombolytic monotherapy and thrombolytic - RAAS-i combination. Meta-analysis (24 studies; = 3,007) confirmed increased risk with RAAS-i (OR: 3.12; 95% CI: 2.01-4.85). Case review ( = 60) showed mainly orofacial presentation ( = 59) within 3 hours, with 42 receiving RAAS-i and 16 requiring advanced airway management. CONCLUSION: This analysis suggests a consistent association increased angioedema risk with thrombolytic-RAAS-i combination therapy. Findings underscore the importance of careful risk assessment and monitoring in patients receiving RAAS-i therapy, especially those on ACEIs.
Expert Opin Drug Saf
· 2026 Mar · PMID 41064961
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INTRODUCTION: Obesity is one of the most common chronic conditions that raises the risk of cardiometabolic issues. Because of their ability to encourage weight loss through urine glucose excretion, sodium - glucose cotra...INTRODUCTION: Obesity is one of the most common chronic conditions that raises the risk of cardiometabolic issues. Because of their ability to encourage weight loss through urine glucose excretion, sodium - glucose cotransporter 2 (SGLT2) inhibitors, which were first approved for the treatment of type 2 diabetes, have become a viable off-label option for managing obesity. AREAS COVERED: This review examines the safety profile of SGLT2 inhibitors for weight reduction in non-diabetic, overweight/obese adults. A comprehensive search on PubMed, EMBASE, the Cochrane Library, and Scopus (January 2015 - January 2025) for RCTs, systematic reviews, and meta-analyses was performed. It details the potential adverse effects of these medications, including euglycemic ketoacidosis, moderate hypotension, vaginal and urinary tract infections, and worries regarding lower limb amputations and renal function. There are still unknowns about the long-term impacts on cardiovascular outcomes, lipid profiles, and bone health, which emphasizes the need for further extensive, focused studies in non-diabetic individuals. EXPERT OPINION: SGLT2 inhibitors offer a modest but clinically meaningful avenue for weight management in select individuals. Broader adoption in routine obesity care will likely require further research to clarify benefits versus risks, develop patient-specific treatment algorithms, and ensure robust monitoring of potential adverse events.
Expert Opin Drug Saf
· 2025 Sep · PMID 41017677
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BACKGROUND: Sacubitril/valsartan, an angiotensin receptor-neprilysin inhibitor, is used for heart failure with reduced ejection fraction. Emerging evidence suggests potential ototoxicity, including hearing loss and vesti...BACKGROUND: Sacubitril/valsartan, an angiotensin receptor-neprilysin inhibitor, is used for heart failure with reduced ejection fraction. Emerging evidence suggests potential ototoxicity, including hearing loss and vestibular disorders, which remain underreported and poorly characterized. RESEARCH DESIGN AND METHODS: Our objective was to compare auditory adverse event (AE) reports associated with sacubitril/valsartan versus those associated with lisinopril and losartan. A retrospective active-comparator disproportionality analysis was conducted using individual case safety reports (ICSRs) from the U.S. FDA Adverse Event Reporting System (FAERS) via OpenFDA (2015Q3-2023Q3). The Medical Dictionary for Regulatory Activities (MedDRA) terms identified AEs related to hearing impairment, vestibular disorders, and hypoacusis. Adjusted reporting odds ratios (aRORs) and 95% confidence intervals (CIs) were estimated using logistic regression, adjusting for age, sex, hypertension, and heart failure. Bayesian methods complemented the analysis. RESULTS: Among 55,101 ICSRs, 28,091 involved sacubitril/valsartan, with 590 (1.07%) reports of hearing impairment and 4,732 (8.58%) vestibular disorders. Compared to lisinopril, sacubitril/valsartan had higher aRORs for hearing impairment (2.35), vestibular disorders (2.58), and hypoacusis (15.03). Similar elevated risks were found versus losartan. Bayesian analysis confirmed these patterns. CONCLUSIONS: Sacubitril/valsartan may be associated with a higher risk of auditory AEs than lisinopril and losartan. These findings warrant further confirmation through pharmacoepidemiologic studies.
Bouden S, Hajjem A, Rouached L
… +6 more, Ben Tekaya A, Ben Dhia S, Mahmoud I, Tekaya R, Saidane O, Abdelmoula L
Expert Opin Drug Saf
· 2025 Oct · PMID 41001848
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BACKGROUND: The aim of our study was to determine the prevalence of hypersensitivity reactions in patients with chronic rheumatic diseases (CRD) treated with biologic therapies, and to evaluate the associated factors. RE...BACKGROUND: The aim of our study was to determine the prevalence of hypersensitivity reactions in patients with chronic rheumatic diseases (CRD) treated with biologic therapies, and to evaluate the associated factors. RESEARCH DESIGN AND METHODS: A 6-year retrospective, single-center study was performed, including patients with CRD treated with biologic therapies. RESULTS: A total of 151 patients (109 women and 42 men) with a mean age of 53.2 ± 13.6 years were included. They were followed for rheumatoid arthritis (59.6%), spondyloarthritis (31.8%), juvenile idiopathic arthritis (6%), rhupus syndrome and scleroderma (1.3% each). Anti-TNF alpha agents were the most frequently prescribed biologic class (67.5%). However, anti-CD20 (Rituximab) was the most frequently prescribed molecule (23.2%). Hypersensitivity reactions occurred in 16.6% ( = 25), mainly systemic (72%) and immediate (84%). The positivity of the rheumatoid factor ( = 0.01), and the axial phenotype of spondyloarthritis ( = 0.01) were significantly associated with the occurrence of hypersensitivity reactions. Infliximab was the biologic agent most associated with hypersensitivity reactions ( = 0.002). Etanercept was most frequently associated with local hypersensitivity reactions ( = 0.04). Concomitant Methotrexate use significantly decreased the risk of hypersensitivity reactions ( = 0.01). CONCLUSIONS: Considering the predictive factors of hypersensitivity reactions to biologics in clinical practice could help anticipate risks and improve patient safety.
Durante JC, Gomes Dantas A, Coelho Inouye F
… +5 more, Varallo FR, Pereira LRL, Inocenti Miasso A, de Almeida MS, Barboza Zanetti MO
Expert Opin Drug Saf
· 2025 Sep · PMID 40996880
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BACKGROUND: Anxiety and insomnia are global health challenges often managed in Primary Health Care (PHC). Benzodiazepines (BZD) are commonly prescribed, but prolonged use increases risks such as cognitive impairment, dep...BACKGROUND: Anxiety and insomnia are global health challenges often managed in Primary Health Care (PHC). Benzodiazepines (BZD) are commonly prescribed, but prolonged use increases risks such as cognitive impairment, dependence, and tolerance. This study assessed PHC users with prolonged BZD use for anxiety or insomnia, focusing on dependence, effectiveness, and cognitive function. RESEARCH DESIGN AND METHODS: A cross-sectional study was conducted with 144 prolonged BZD users in PHC. Data collection included sociodemographic and clinical questionnaires, alongside instruments assessing dependence, cognition, insomnia, and anxiety. Logistic regression analyses were performed. RESULTS: Participants had a mean age of 64.3 years (SD=10.97) and average BZD use duration of 10 years. Prevalence of polypharmacy (54.9%), high anticholinergic load (41%), falls (29.2%), and alcohol use (33.4%) was observed. Falls were linked to severe problematic BZD use, while aging, cognitive impairment, mild insomnia, and lower anxiety were linked to less severe use. Severe insomnia correlated with extreme concerns about medication availability. Older age, white race, and better insomnia or anxiety profiles reduced non-adherence risks, whereas illiteracy increased them. Severe withdrawal symptoms elevated fall risk. CONCLUSIONS: Findings stress the need for BZD deprescription.
Expert Opin Drug Saf
· 2026 Mar · PMID 40965310
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INTRODUCTION: Antithyroid drugs (ATDs) constitute the treatment option for the management of pregnant women with hyperthyroidism of Graves' disease. The risk of teratogenic side effects to the use of ATDs in pregnancy ha...INTRODUCTION: Antithyroid drugs (ATDs) constitute the treatment option for the management of pregnant women with hyperthyroidism of Graves' disease. The risk of teratogenic side effects to the use of ATDs in pregnancy has challenged the clinical recommendation on the choice of drug and treatment strategy. AREAS COVERED: Overview and methodological discussion of the evidence gathered within the last 50 years on the teratogenic risk of ATDs based on sources of real-world data (RWD) and different study designs. EXPERT OPINION: The level of evidence has evolved within the last century and current state of the art points toward a teratogenic role of Methimazole and Carbimazole. On the other hand, evidence to substantiate the teratogenic role of PTU is less comprehensive and less clear. The findings challenge clinical guidance, and uncertainties prevail for recommendations on the choice of ATD and individual patient management in and around early pregnancy. Future research should focus on the combined use of different sources of RWD in large cohorts and across populations. Detailed assessment of exposure and outcome and considerations on other thyroidal and non-thyroidal related factors in the associations observed are important to inform and support the clinical guidance.
Megna M, Cecere D, D'Agostino M
… +5 more, Tommasino N, Lauletta G, Esposito V, Bianco M, Potestio L
Expert Opin Drug Saf
· 2026 Feb · PMID 40847911
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INTRODUCTION: Bimekizumab is the latest biologics approved for the management of moderate-to-severe plaque psoriasis. Its unique mechanism of action simultaneously inhibition of interleukin (IL)17A and IL17F] offers a po...INTRODUCTION: Bimekizumab is the latest biologics approved for the management of moderate-to-severe plaque psoriasis. Its unique mechanism of action simultaneously inhibition of interleukin (IL)17A and IL17F] offers a potentially deeper suppression of cutaneous immune activation compared to selective IL17A inhibition alone. While clinical trials demonstrated excellent results in terms of efficacy and safety, real-world data are mandatory to assess its performance in broader patient populations, including those excluded from trials. AREAS COVERED: This narrative review summarizes findings from real-life studies on bimekizumab in moderate-to-severe plaque psoriasis. Extensive literature research was conducted on the main databases, including PubMed, Embase, Ovid, Scopus, Google Scholar and the Cochrane Library, until April 2025. EXPERT OPINION: Bimekizumab has rapidly gained relevance as a highly effective and fast-acting option in psoriasis management, with durable outcomes across heterogeneous patient profiles. The emerging number of real-world evidence reinforces its value in routine practice and supports its positioning as a valuable weapon among the armamentarium of biological therapies.
Expert Opin Drug Saf
· 2026 Jan · PMID 40834041
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INTRODUCTION: Multiple sclerosis (MS) is a chronic, immune-mediated disease of the central nervous system, characterized by relapses or progressive neurological decline. Over recent decades, high-efficacy immunosuppressi...INTRODUCTION: Multiple sclerosis (MS) is a chronic, immune-mediated disease of the central nervous system, characterized by relapses or progressive neurological decline. Over recent decades, high-efficacy immunosuppressive therapies have dramatically reduced relapse rates and curtailed new MRI lesion activity in MS, but also raise safety concerns regarding infections, malignancy, and other serious adverse events. AREAS COVERED: This review discusses immunosuppressants in MS, from older cytotoxic agents (azathioprine, cyclophosphamide, mitoxantrone) to newer therapies (cladribine, alemtuzumab, and anti-CD20 monoclonal antibodies). Key efficacy data are summarized, alongside risks of hematologic, hepatic, and autoimmune toxicities. Emerging evidence on malignancy risk is highlighted, including therapy-related acute leukemias (mitoxantrone), urothelial tumors (cyclophosphamide), and potential neoplasms linked to newer agents. Strategies for patient selection, screening, and long-term vigilance are examined to balance high-efficacy disease control with acceptable safety margins. EXPERT OPINION: Immunosuppressants remain vital for certain MS phenotypes, especially those with highly active or refractory disease. Although novel agents offer more selective mechanisms, they still pose notable risks demanding careful monitoring and individualized care. Ongoing research, including predictive biomarkers and post-marketing surveillance, will refine patient selection and mitigate adverse events. With judicious use and robust safety protocols, clinicians can achieve durable disease control while minimizing long-term toxicities.
Sawhney A, Gupta R, Mahajan P
… +3 more, Agrawal A, Cossu S, Lakkireddy DR
Expert Opin Drug Saf
· 2026 Feb · PMID 40791031
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INTRODUCTION: Left atrial appendage occlusion (LAAO) is a viable alternative to anticoagulation for treatment in patients with non-valvular atrial fibrillation (NVAF) who cannot tolerate anticoagulation. Post-procedure p...INTRODUCTION: Left atrial appendage occlusion (LAAO) is a viable alternative to anticoagulation for treatment in patients with non-valvular atrial fibrillation (NVAF) who cannot tolerate anticoagulation. Post-procedure patients are generally prescribed oral anticoagulation (OAC) for 45 days, while the device is undergoing endothelialization, following which patients are continued on antiplatelet agents. Recommendations for antithrombotic agents following LAAO arrived by consensus, which are not tolerated by all patients. AREAS COVERED: This review covers the safety profile of antithrombotic therapy options after LAAO. We discuss the side effect profiles including device-related thrombosis (DRT), bleeding, and thromboembolic events. The new randomized controlled trials and meta-analysis compared combinations of DOAC with single antiplatelet therapy (SAPT), dual antiplatelet therapy (DAPT), VKA, or only SAPT and studied the incidence of major bleeding, DRT, and thromboembolic events. This review is a comprehensive summary of different antithrombotic agents' combinations along with the duration recommendations and emphasizes the importance of a discussion among involved team members and patients. EXPERT OPINION: In patients with NVAF undergoing LAAO, initial post-procedural antithrombotic monotherapy with DOAC is associated with low rates of thromboembolism, DRT, and major bleeding followed by DAPT. DAPT is associated with lower incidence of thromboembolic events in comparison to SAPT.
Ferrero S, Barra F, Vatteroni G
… +4 more, Rosato FP, Evangelisti G, Paudice M, Vellone VG
Expert Opin Drug Saf
· 2026 Feb · PMID 40788342
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INTRODUCTION: Medical therapy is crucial in the long-term management of endometriosis, and its clinical efficacy must be balanced with a favorable safety profile. AREAS COVERED: This review aims to provide a comprehensiv...INTRODUCTION: Medical therapy is crucial in the long-term management of endometriosis, and its clinical efficacy must be balanced with a favorable safety profile. AREAS COVERED: This review aims to provide a comprehensive overview of available drugs for the treatment of endometriosis, with an emphasis on their safety. A literature search was conducted using MEDLINE. EMBASE. and the Cochrane Library. Reference lists of relevant articles and recent book chapters were also examined. EXPERT OPINION: First-line therapies include combined contraceptives and progestins, both effective in reducing pain. Combined contraceptives commonly cause breakthrough bleeding, nausea, headaches, breast tenderness, and libido changes. Progestins may lead to depression, decreased libido, weight gain, breast tenderness, and lipid alterations. Gonadotropin-releasing hormone agonists are second-line options but are limited by hypoestrogenic side effects, including vasomotor symptoms, urogenital atrophy, and bone mineral density (BMD) loss. Add-back therapy with norethindrone acetate or low-dose combined contraceptives mitigates these effects. GnRH antagonists provide immediate suppression without flare-up and may improve adherence; however, hot flushes and BMD loss remain concerns. While all hormonal therapies are suppressive rather than curative, optimizing safety and tolerability is essential for sustained use and symptom control.
Expert Opin Drug Saf
· 2026 Feb · PMID 40778834
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INTRODUCTION: Hyperglycemia in pregnancy, including gestational diabetes mellitus (GDM) and pregestational diabetes, significantly impacts maternal and neonatal outcomes, necessitating effective management strategies. In...INTRODUCTION: Hyperglycemia in pregnancy, including gestational diabetes mellitus (GDM) and pregestational diabetes, significantly impacts maternal and neonatal outcomes, necessitating effective management strategies. Insulin is the first-line therapy; however, adherence barriers, cost, and route of administration challenges have driven interest in oral agents like metformin and glyburide. These agents offer practical alternatives but raise questions about long-term safety and fetal exposure. AREAS COVERED: This review evaluates the pharmacokinetics, pharmacodynamics, and clinical outcomes of metformin and glyburide, focusing on their roles in GDM, pregestational diabetes, polycystic ovary syndrome (PCOS), and obesity. Maternal outcomes, neonatal impacts, and long-term offspring health were assessed to determine the safety of these therapies. EXPERT OPINION: Metformin reduces insulin dependency and weight gain during pregnancy but raises concerns about short and long-term offspring impacts, such as increased SGA rates (22% vs. 5%), altered growth patterns, and offspring neurocognition. Glyburide is effective for glycemic control but carries higher neonatal hypoglycemia risks and lacks robust long-term safety data. Both agents hold promise as alternatives to insulin, particularly in resource-limited settings. However, further research is needed to address knowledge gaps, optimize their use, and ensure safe integration into clinical practice.
Barbieri MA, Battini V, Carnovale C
… +9 more, Cocco M, Papoutsi DG, Heckmann NS, Dong G, Rossi A, Peker S, Van Manen RP, Thapar S, Sessa M
Expert Opin Drug Saf
· 2026 Feb · PMID 40778768
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INTRODUCTION: The integration of artificial intelligence (AI) into pharmacovigilance (PV) has advanced rapidly in recent years. AI tools have the potential to transform signal management by enabling faster and more accur...INTRODUCTION: The integration of artificial intelligence (AI) into pharmacovigilance (PV) has advanced rapidly in recent years. AI tools have the potential to transform signal management by enabling faster and more accurate signal management and decision-making. However, the regulatory landscape governing these technologies remains complex. AREAS COVERED: This article presents available AI tools for signal management, provides an overview of the regulatory landscape of these tools, and explores stakeholder perspectives on the challenges and opportunities posed by AI regulations. On 23 July 2024, we conducted a Google search of the top 2,000 results using the query 'AI pharmacovigilance service provider.' Two searches were performed in Ovid MEDLINE to identify articles published between 1 January 2022, and 23 July 2024, using ad hoc queries. EXPERT OPINION: AI tools are now available to support all critical activities in signal management. However, regulatory discrepancies and variations persist across different regions. The findings underscore the urgent need for ongoing international collaboration to harmonize regulatory frameworks and ensure the safe and ethical implementation of AI in PV. As AI technologies continue to evolve, addressing these regulatory and operational challenges will be essential to fully realize their potential in enhancing drug safety and improving healthcare outcomes worldwide.
Expert Opin Drug Saf
· 2026 Jan · PMID 40762522
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INTRODUCTION: Hydroxychloroquine (HCQ) is prescribed in systemic autoimmune diseases for disease-modifying benefits. However, long-term HCQ use can cause irreversible retinal toxicity. AREAS COVERED: Key articles were id...INTRODUCTION: Hydroxychloroquine (HCQ) is prescribed in systemic autoimmune diseases for disease-modifying benefits. However, long-term HCQ use can cause irreversible retinal toxicity. AREAS COVERED: Key articles were identified through searches of publications in PubMed and Embase from January 2000 to May 2025. Data indicate that retinopathy risk is low during the first 5-10 years of therapy but rises with longer exposure. High daily dose ( >5 mg/kg real weight), long-term use ( >5 years), renal impairment, and tamoxifen use are key risk factors. Guidelines emphasize weight-based dosing (≤5 mg/kg/day) and regular ophthalmologic screening. The American Academy of Ophthalmology (AAO) recommends baseline fundus exam and annual screening after 5 years of HCQ use if no high-risk features, using spectral-domain optical coherence tomography (SD-OCT) and automated visual fields as primary tests. Four recommended screening modalities by AAO and Royal College of Ophthalmologists include SD-OCT, fundus autofluorescence, automated visual fields, and multifocal electroretinography. EXPERT OPINION: Despite advancements in understanding and detecting HCQ retinopathy, challenges remain in defining a truly safe dose, achieving early detection, and ensuring adherence to screening guidelines. Ongoing research into imaging biomarkers, genetic susceptibility, and AI-driven tools aims to enhance early detection and personalize screening, ultimately improving outcomes and reducing vision loss.