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: Vismodegib and sonidegib are currently the only Hedgehog inhibitors (HHIs) approved by the U.S. Food and Drug Administration (FDA) for the treatment of locally advanced BCC (laBCC). However, there is limited systematic research comparing the adverse drug events (ADEs) associated with these two inhibitors.

Research design and methods: Data were extracted from the Food and Drug Administration Adverse Event Reporting System (FAERS) for the period from 2019 to the second quarter of 2024. Disproportionality analysis was conducted to compare ADEs between vismodegib and sonidegib.

Results: The occurrence of ADEs was notably higher among patients aged ≥ 65 years (72.98%) and males (60.17%). The most frequently reported ADEs associated with HHIs included skeletal muscle and joint diseases and nervous system disorders, particularly muscle spasms and dysgeusia. Differences in adverse reactions between vismodegib and sonidegib were observed, mainly in nervous system, gastrointestinal system, skin and subcutaneous tissue, and renal and urinary disorders.

Conclusions: This analysis, using the FAERS database, enhances understanding of the ADE profiles associated with both vismodegib and sonidegib. Further research is needed to validate the hypotheses generated by this study.

Background: Setmelanotide is approved for genetically determined obesity. While clinical trials and clinical evidence and practice provide some insights, a comprehensive assessment of its adverse event profile is needed that led to carrying out an assessment of reported adverse events in the USFDA Adverse Event Reporting System database, case reports and clinical trials.

Research design and methods: Multi-faceted analyses were carried out as follows: disproportionality measures employing frequentist and Bayesian methods; systematic review and meta-analysis (Medline, Cochrane CENTRAL and Google Scholar) generated-pooled estimates [proportion with 95% confidence intervals (CI)]; and published reports with adverse events to setmelanotide.

Results: The disproportionality analysis (n = 228) identified skin hyperpigmentation, injection-site reactions, nausea, melanocytic nevus and ephelides as key safety signals. Meta-analysis (seven trials; n = 185) confirmed high rates of injection-site reactions (96%; 95% CI: 89, 100), skin hyperpigmentation (62%; 95% CI: 43, 78), nausea (36%; 95% CI: 24, 49), vomiting (26%; 95% CI: 18, 34), and diarrhea (21%; 95% CI: 14, 29). Individual case reports corroborated these findings.

Conclusion: This study provides a detailed overview of setmelanotide's adverse event profile, highlighting the need for careful patient monitoring, emphasizing the importance of ongoing safety surveillance for at least 1.5 years, and further research to refine patient management strategies.

Background: Riociguat is a novel soluble guanylate cyclase stimulator approved for the treatment of pulmonary arterial hypertension (PAH). Despite its widespread use, there has been a lack of large-scale studies assessing the adverse events (AEs) associated with this medication.

Research design and methods: This study aimed to evaluate the AEs related to Riociguat by analyzing data from the FDA Adverse Event Reporting System (FAERS) from Q4 2013 to Q1 2024. A total of 12,149 AE reports were analyzed using four different disproportionality signal detection methodologies to identify significant AEs associated with Riociguat.

Results: The analysis revealed 117 preferred terms (PTs) with significant disproportionality signals across all four methods. Among these, common AEs included 'headache,' 'dizziness,' 'hypotension,' 'nausea,' 'fall,' and 'loss of consciousness.' Notably, several unexpected AEs, such as 'fatigue,' 'malaise,' 'asthenia,' 'feeling abnormal,' and 'pain in extremity,' were identified, which were not highlighted in the product's package insert. Additionally, gender-specific differences were observed in certain adverse events.

Conclusions: This study offers insights into Riociguat's side effects. Clinicians should monitor patients closely for unexpected symptoms like limb pain and fatigue, paying particular attention to male patients, as some AEs occur more frequently in this group.

Introduction: Immune checkpoint inhibitors have become an increasingly effective treatment for various malignancies, although their use is associated with a range of organ toxicities. As these therapies become more prevalent, it is critical to establish appropriate management and long-term surveillance strategies for patients who develop immune-related adverse events.

Areas covered: This review explores the chronic sequelae that may result from immune-related adverse events and focuses specifically on their persistence, outcomes, and implications for future research. A literature review was conducted using PubMed to identify relevant articles from within the last 10 years.

Expert opinion: While acute management of irAEs has improved over the past decade, there is a major gap in understanding and addressing their chronic sequelae. Challenges in studying these sequelae include the complexity of cancer care, overlapping clinical presentations, and previously, a lack of long-term data. Continued research from large multicenter studies and dedicated databases can identify high-risk patients, inform risk-benefit discussions, refine management strategies, and pave the way for evidence-based, long-term care.

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.

Background: Immune checkpoint inhibitors (ICIs)-associated cardiotoxic events (CEs) are of increasing concern. Existing research about glucocorticoids (GCs) on immunotherapy focused on ICIs' efficacy and patients' outcome. The influence of GCs on ICIs-associated CEs and myocardial damage (MD) remains unknown.

Research design and methods: This single-center retrospective study included patients treated with ICIs from 2018 to 2022, with follow-up period ending on 30 June 2023. The incidence, risk factors of ICIs-associated CEs, especially MD were described. Additionally, the impact of baseline GCs was assessed by propensity score matching (PSM) to mitigate intergroup differences and ensure comparability.

Results: Among 1018 patients, 204 (20.04%) experienced ICIs-associated CEs, including 71 (6.97%) with MD. The mean follow-up time was 40.39 (95% CI 38.47-42.31) weeks. The median time to onset of MD was the shortest at 12.57 weeks (IQR 5.29-25.14). Tumor type, co-medication with platinum and angiogenesis inhibitors may be influential factors of MD. After PSM, the relative risks of CEs (OR 0.4625,95%CI 0.2514-0.7235, p = 0.0020) and MD (OR 0.3254, 95% CI 0.1190-0.8898, p = 0.0378) in GCs1 ≥ 20 mg group were both significantly lower than those in GCs1 < 20 mg.

Conclusion: GCs ≥ 20 mg during the first ICIs treatment cycle is significantly associated with the reduced risks of both ICIs-associated CEs and MD.

Introduction: Knee osteoarthritis (KOA) is a highly prevalent condition worldwide, resulting in a significant symptom burden and diminished quality of life. Mainstays of KOA management include weight loss, exercise, physical activity, and simple analgesia, with joint replacement as a last resort. Intra-articular injections, especially corticosteroids, have been increasingly used to provide symptomatic relief when simple analgesia fails. However, the efficacy and safety of intra-articular corticosteroid injections (IACS) remain poorly established.

Areas covered: This narrative literature review will evaluate the current available literature, outlining evidence on the use of IACS in KOA as well as its clinical efficacy, safety, adverse effects and potential alternative injections. Articles included were sourced from the University of Sydney Library database, Medline via Ovid, and Scopus, between 2000 and 2026.

Expert opinion: Overall, while IACS may only provide short-term pain relief, evidence suggests that long-term use should be avoided to prevent chondrotoxicity and further progression of osteoarthritis.