Expert Opinion on Drug Safety最新文献

Background: [¹⁷⁷Lu]Lu-PSMA-617 (Pluvicto), a new radioligand therapy that targets prostate-specific membrane antigen (PSMA), has been approved to treat metastatic castration-resistant prostate cancer (mCRPC). However, the real-world safety profile of [¹⁷⁷Lu]Lu-PSMA-617 has not been systemically evaluated.

Research design and methods: Adverse event reports for [¹⁷⁷Lu]Lu-PSMA-617 were retrieved from April 2022 to June 2024 from The Food and Drug Administration Adverse Event Reporting System (FAERS) database. Disproportionality analysis was conducted by four algorithms: reporting odds ratio (ROR), proportional reporting ratio (PRR), Multi-Item Gamma Poisson Shrinker (MGPS) and Bayesian Confidence Propagation Neural Network (BCPNN). Subgroup analysis, time-to-onset and sensitivity analysis were also employed.

Results: 384,2712 adverse event reports were retrieved, of which 870 were associated with [¹⁷⁷Lu]Lu-PSMA-617 in prostate cancer patients. We identified known adverse events (fatigue/asthenia, anemia, thrombocytopenia and nausea) and discovered adverse events not specified on the label (loss of libido, hydronephrosis, supraventricular tachycardia, tumor lysis syndrome, and tumor flare). Subgroup analysis revealed high-risk signals included stomatitis, pneumonia, leukopenia, and sepsis for patients aged over 85. The median onset time was 55 days (interquartile range 24-124 days).

Conclusions: The findings provide new insights into the adverse events of [¹⁷⁷Lu]Lu-PSMA-617 and valuable references for clinical applications of radioligand therapy for mCRPC.

Background: Topical minoxidil, approved by the FDA in the 1980s, has been widely used to manage androgenetic alopecia. While effective, several adverse events (AEs) related to its use, especially those not well-documented on product labels, remain a concern.

Objective: This study aimed to evaluate the safety of topical minoxidil by analyzing AEs reported in the FDA Adverse Event Reporting System (FAERS) from 2004 to 2024, focusing on identifying potential risk signals not highlighted on current product labels.

Methods: Adverse event reports (AERs) from FAERS, where topical minoxidil was identified as the primary suspect, were analyzed. Disproportionality analysis methods, Reporting Odds Ratio (ROR), Proportional Reporting Ratio (PRR), Bayesian Confidence Propagation Neural Network (BCPNN), and Multi-Item Gamma Poisson Shrinker (MGPS), were used to assess the relationship between minoxidil and reported AEs.

Results: Among 45,130 reports, most were from males (50.88%) and showed a significant increase in incidents since 2015. Newly identified AEs, such as application site acne and cysts, were observed. These AEs are not well represented on product labels.

Conclusion: The study identified previously unreported AEs linked to topical minoxidil, underscoring the need for updated patient information and regulatory reassessment to enhance safety and inform clinical practices.

Background: As fundamental chemotherapy drugs, paclitaxel and its derivatives are essential for cancer treatment. This analysis comprehensively evalutaed the toxicity spectrum of taxanes from the perspective of clinical trials and the real-world.

Research design and methods: Pooled-analyses were performed to estimate incidences of adverse events (AEs) with random-effect models after searching databases. Reports of AEs were retrospectively obtained from the US Food and Drug Administration's (FDA's) Adverse Event Reporting System (FAERS) database and positive signals were quantified by employing three algorithms.

Results: A total of 36 studies involving 10,828 patients were analyzed in pooled-analysis and 58,835 case reports were retrieved. Leukopenia (59.69, 95% confidence interval 41.34-75.69) and neutropenia (29.69, 23.31-36.99) ranked first among all grades and severe AEs, respectively. Alopecia, regardless of grades, had the highest estimated incidence of non-hematological AEs. The estimated incidences of AEs of Nab-paclitaxel tended to be higher than other formulations, especially neutropenia (46.53, 35.01-58.42). Docetaxel had the least signals but alopecia and depression have quantified several signals.

Conclusions: The safety of nab-paclitaxel was beyond expectation and unusual signals of alopecia and depression of docetaxel need to be paid attention to. Results of clinical trials and FAERS indicated consistency between premarket and postmarket studies.

Background: Myasthenia gravis (MG) is a rare but serious adverse event (AE) of statins. Yet, its pharmacovigilance and clinical features remain unknown.

Research design and methods: Data were extracted from the FDA Adverse Event Reporting System (FAERS) (2004 Q1-2023 Q4), and disproportionality analyses were conducted. Case reports on statin-associated MG dated up to 31 December 2023 were retrieved for retrospective analysis.

Results: Data from FAERS showed 178,802 AEs of statins, with musculoskeletal disorders being the most common. Compared to other cholesterol-lowering drugs, statins exhibited a significant increase in MG, with 128 reports included, with pravastatin having the highest proportion. Sixteen cases from 12 studies demonstrated atorvastatin was the most frequently reported agent associated with MG. The median age was 58 years, with a male predominance. The main clinical symptoms were ocular muscle weakness, lasting from 1 week to 3 years. Twelve patients were acetylcholine receptor (AChR) antibody positive. All patients discontinued statins, 14 patients received treatment comprising cholinesterase inhibitors and immunosuppressive drugs. Nine patients achieved recovery, and five patients relapsed after steroid reduction or statins re-administration.

Conclusions: In the real-world pharmacovigilance study, statins are associated with increased reporting of MG. Early identification and timely treatment are crucial for the safe use of statins.

Introduction: This study aimed to reevaluate the clinical efficacy and safety of omadacycline in treating acute bacterial infections.

Methods: We searched PubMed, Embase, Cochrane Library, Web of Science, and Clinical Trials up to 1 January 2024, including only randomized controlled trials comparing OMC with other antibiotics in adults. Primary outcomes were clinical and microbiological responses; secondary outcomes included adverse events.

Results: Seven RCTs with 2957 patients met the inclusion criteria. OMC showed a slightly better clinical response at the post-therapy evaluation phase in the clinically evaluable population (RR = 1.03, 95% CI = 1.01-1.05, I² = 0%). Microbial eradication rates for Gram-positive and Gram-negative infections showed no significant differences between OMC and comparators. Safety analysis revealed no significant differences in overall AEs, treatment-related AEs, serious AEs, or drug discontinuation due to AEs. However, OMC had a lower risk of diarrhea (RR: 0.48, 95% CI = 0.23-1.00, I² = 65%). All-cause mortality did not differ significantly between OMC and comparators.

Conclusions: OMC is a safe and effective treatment for acute bacterial infections, comparable to other antibiotics.

Registration: This study has been registered in the online systematic review database (Prospective Register of Systematic Reviews [PROSPERO]), and the registration number is CRD42024575416.

Introduction: Biosimilars have transformed treatment modalities across various medical fields such as oncology, rheumatology, and immunology. Despite their potential for reducing healthcare costs, concerns persist regarding their ability to induce an immune response, which could affect efficacy and safety. This review critically evaluates the current evidence on the immunogenicity of biosimilars and discusses the regulatory frameworks guiding their approval and monitoring.

Areas covered: This review includes studies from databases like Scopus, PubMed, Web of Science, and ScienceDirect, published up to April 2024. It explores the 'totality of the evidence' approach used by regulatory bodies like the FDA and EMA, detailing analytical, preclinical, and clinical assessments that ensure biosimilars' similarity to their reference products in terms of structure, function, and clinical outcomes. The review also addresses the challenges and limitations in current research methodologies and the implications of immunogenicity on therapeutic efficacy and patient safety.

Expert opinion: While substantial evidence confirms the safety and efficacy of biosimilars, the review emphasizes the need for continuous regulatory vigilance and advanced methodologies in post-marketing surveillance to capture long-term immunogenicity data effectively. It advocates for integrating cutting-edge analytical techniques and personalized medicine to better manage immunogenic risks associated with biological therapies.

Introduction: Psychotic symptoms in Parkinson's disease are common and are comprised of hallucinations and delusions. Psychosis is a major cause of disability in PD and is primarily due to an interaction with PD medication. The decision to treat psychosis is determined by the severity of the symptoms, impact on quality of life and tolerance for the treatment. Initial management involves a reduction in non-PD psychoactive medications and/or modification of PD medications. Pharmacotherapy is primarily limited to atypical antipsychotics and pimavanserin.

Areas covered: This review will focus on the phenomenology of Parkinson's disease psychosis and its management.

Expert opinion: Pimavanserin is the only Food and Drug Administration medication approved for the treatment of PDP. Among the antipsychotics, only clozapine and pimavanserin demonstrated efficacy in the treatment of PDP. Despite lack of evidence for efficacy in PDP, quetiapine is commonly used because it does not worsen motor function and lacks the blood monitoring requirement of clozapine. Pimavanserin is the first-line treatment for mild psychotic symptoms that do not require a rapid response and quetiapine and clozapine for psychosis that requires improvement in a short period of time. Antipsychotics used to treat PDP should demonstrate safety, motor tolerability and efficacy over time.

Introduction: An increasing number of patients with polyarticular course juvenile idiopathic arthritis are treated with biologics with great efficacy. Consequently, the importance regarding safety data in general as well as especially serious infections, incident autoimmune processes, or malignancies rises. In children, this is crucial concerning occurrences that manifest rarely and only after a prolonged latency period.

Areas covered: This study aims to analyze safety under therapy with the five most commonly used biologicals for the treatment of juvenile idiopathic arthritis in Germany: abatacept, adalimumab, etanercept, golimumab, and tocilizumab, and a control cohort, who received methotrexate. For this, data from the Biologics in Pediatric Rheumatology (BiKeR) Registry were analyzed with a focus on potential adverse drug reactions like serious infections, autoimmune processes or malignancies.

Expert opinion: Besides JIA category-specific differences, investigating side effects like severe infections and the development of additional autoimmune processes due to therapy is crucial. Future clinical randomized double-blinded studies are essential for direct drug comparisons, enabling optimal individualized therapy considering comorbidities and individual risks. Large patient data over a (life-)long period beyond childhood are particularly important, especially concerning the risk of malignancy after prolonged latency.

Background: Previous studies have explored the association between levetiracetam (LEV) and severe cutaneous adverse reactions (SCARs). However, most investigations have relied on clinical trial data or case reports from individual medical centers. Consequently, the precise relationship between LEV and SCARs in real-world settings remains elusive.

Research design and methods: Data from the FDA Adverse Event Reporting System (FAERS) and EudraVigilance databases were analyzed, focusing on LEV-associated SCAR events utilizing disproportionality analysis methods.

Results: This study identified a significant correlation between LEV and SCARs (p < 0.05). However, combined analyses with other antiepileptic drugs revealed that the association of LEV with SCARs was comparatively weaker (p < 0.05). Univariate logistic regression analysis indicated that males, individuals aged 45 ~ 65 years, and combination therapy with eslicarbazepine, phenytoin, carbamazepine, and lamotrigine significantly increased the risk of developing SCARs (p < 0.05). Notably, SCARs were most likely to occur within the initial week of LEV treatment (39.39%).

Conclusions: Despite certain limitations, this study offers updated insights into the association between LEV and SCARs. These findings underscore the significance of monitoring and actively managing LEV-associated SCARs to promote its safe and effective use.

Background: Alzheimer's disease (AD) is the most common form of dementia. The combination of Donepezil and Memantine is the only FDA-approved therapy for AD, but its adverse drug reactions (ADRs) lack systematic analysis. This study carried out drug combination analysis for AD population to provide evidence support for clinical safety of drug use.

Research design and methods: Using FAERS database reports (January 2004-January 2024) with Donepezil and Memantine as primary suspected drugs, four disproportionality analysis methods - ROR, PRR, BCPNN, and EBGM - were applied to identify positive ADR signals. Subgroup analyses were conducted by age and gender.

Results: A total of 712 reports were analyzed (54.6% female, 55.1% aged 65-85). Across the AD population, 42 ADRs were identified, including hypertensive crisis, hyperglycemia, hyperosmolar nonketotic syndrome, proteinuria, and hydronephrosis, many of which were newly reported. Subgroup analysis revealed prostate hypertrophy, acute kidney injury, and cerebral infarction in males, while females experienced more severe cardiovascular events, such as complete AV block and ventricular extrasystole. Additional ADRs included hyperkalemia, sinus bradycardia, and extrapyramidal disorders.

Conclusions: Despite partial consistency of combined ADRs for Donepezil and Memantine with instructions, new ADR signals emerged, with significant differences in AD subgroups.