Drugs - Real World Outcomes最新文献

Background: The humanized anti-disialoganglioside-2 monoclonal antibody naxitamab was approved in the USA in 2020 for the treatment of patients with relapsed/refractory high-risk neuroblastoma, limited to the bone or bone marrow, in combination with granulocyte-macrophage colony-stimulating factor. Treatment with naxitamab under expanded access was initiated by physicians from the Children's Hospital of Fudan University, Shanghai, China, in August 2021.

Objective: We reviewed all suspected adverse reactions (ARs) reported to the Y-mAbs Argus Global Pharmacovigilance Safety Database for patients treated with naxitamab under expanded access in China from 1 August 2021 to 31 July 2022.

Methods: We assessed patient demographics and the safety profile of naxitamab over multiple treatment cycles.

Results: At the data cutoff, 41 patients with relapsed/refractory high-risk neuroblastoma had received a total of 150 treatment cycles (451 infusions) of naxitamab. The median number of cycles completed was three; 13 patients (32%) were receiving ongoing naxitamab treatment. The median patient age was 3 years (range 1-9 years) and 63% were female. Overall, ARs were reported in 89/150 cycles (59%); serious ARs were reported in 23/150 cycles (15%). The cumulative reporting rate (ARs/cycle) decreased after 3 versus 12 months of expanded access: all ARs (8.7-4.6), serious ARs (0.9-0.3), hypotension (1.4-1.0), flushing (0.7-0.5), cough (0.6-0.3), pain (0.5-0.2), and hypoxia (0.3-0.2).

Conclusions: During the first 12 months of expanded access treatment in China, 41 patients received naxitamab therapy with a cumulative 451 infusions administered. Over the course of this expanded access program, a reduction in the AR rate, including serious ARs, was observed as more patients were initiated and proceeded to later treatment cycles. While additional research is needed, the observed decrease in the AR rate may be attributed to clinicians' increased knowledge of AR management and hands-on experience with naxitamab-treated patients.

Background and objective: Vildagliptin sustained release (XR), a formulation that provides vildagliptin 100 mg with a once-daily dose administration, is a recent introduction to manage type 2 diabetes mellitus in India. This study aimed to evaluate the effectiveness and tolerability of vildagliptin XR in patients with type 2 diabetes in real-world clinical settings.

Methods: This was an observational, prospective, multicenter, cohort study conducted in India, which included patients with type 2 diabetes uncontrolled on metformin XR monotherapy with glycated hemoglobin (HbA1c) > 7.00%. Vildagliptin XR was added to their ongoing treatment. The primary endpoint was a change in HbA1c from baseline to 3 months. Secondary endpoints were changes in fasting plasma glucose, postprandial plasma glucose, percentage of patients achieving HbA1c < 7.00% at 3 months, and assessment of efficacy, tolerability, and safety.

Results: A total of 1691 patients from 118 centers were enrolled in this study, having a mean (standard deviation) age of 53.10 (11) years and a mean (standard deviation) HbA1c of 8.44 (1.35) %. At the end of the study, vildagliptin XR significantly reduced the mean HbA1c by 1.02% points (95% confidence interval 0.93-1.12; p < 0.001) from baseline. The mean fasting plasma glucose and postprandial plasma glucose levels were significantly reduced by 28.44 mg/dL (95% confidence interval 26.64-30.25; p < 0.001) and 48.45 mg/dL (95% confidence interval 45.91-50.99; p < 0.001), respectively, with vildagliptin XR, at the end of study. During the study duration, 34.7% of patients achieved their glycemic target (HbA1c < 7.0%) and there were three reported adverse events (all mild in severity).

Conclusions: Results demonstrated that vildagliptin XR (100 mg once daily) significantly improved HbA1c and other glycemic parameters in Indian patients with type 2 diabetes and was well tolerated.

Clinical trial registration: The study was registered under the Clinical Trials Registry India (CTRI/2022/01/039112).

Background: Lanadelumab is the only long-term prophylaxis indicated for reduced administration frequency in patients with hereditary angioedema who have been well controlled for > 6 months. Understanding the characteristics of patients who reduce administration frequency will help identify populations where frequency modifications may be appropriate.

Objective: We aimed to describe characteristics of patients who did and did not reduce lanadelumab administration frequency to inform real-world dosing regimens, and characteristics indicative of sustained frequency reduction.

Methods: A retrospective observational study using healthcare insurance data in the USA from the Merative™ MarketScan^® Commercial and Medicare Databases identified patients persistent on lanadelumab for ≥ 18 months. Reduced administration frequency was defined as a ≥ 25% decrease in lanadelumab costs during months 7-12 or 13-18 versus 0-6. Hereditary angioedema attack triggers/symptoms and hereditary angioedema-related healthcare encounters, treatment, and costs were assessed.

Results: Of 54 identified patients, 25 reduced administration frequency. Two patients returned to initial dosing frequency during months 13-18 after reducing during months 7-12. Patients who reduced administration frequency experienced fewer hereditary angioedema attack triggers/symptoms before lanadelumab initiation (baseline) and during months 0-6 than those who did not; they also had a lower mean number of hereditary angioedema-related inpatient admissions, emergency room visits, and outpatient visits during baseline, had fewer claims for acute treatment (60.0% vs 65.5%) and prior long-term prophylaxis (20.0% vs 27.6%), and had lower mean hereditary angioedema treatment costs at baseline ($139,520 vs $233,815) than those who did not.

Conclusions: This real-world analysis suggests that patients with less frequent hereditary angioedema-related healthcare encounters, lower disease activity, and lower costs within 6 months before lanadelumab initiation are more likely to achieve reduced dosing frequency.

Anti-seizure medications (ASMs) are specific types of anticonvulsants used to treat epileptic seizures. However, several studies have shown an association between ASMs and an increased risk of hematological disorders, such as thrombocytopenia, aplastic anemia, and platelet function disorders leading to prolonged bleeding times. This review explores the existing literature on this topic, investigating a wide variety of ASMs, ranging from first-generation medications to newer ones. A comprehensive search was conducted on all the currently approved ASMs using PubMed and Google Scholar: review articles, clinical trials, meta-analysis, observational studies, case reports, and relevant animal studies were identified. We extracted 15 ASMs including valproic acid (VPA), carbamazepine, phenytoin, phenobarbital, diazepam, clonazepam, lamotrigine, levetiracetam, oxcarbazepine, felbamate, topiramate, pregabalin, lacosamide, cannabidiol (CBD), and perampanel that contain considerable literature regarding different coagulopathies. An in-depth review of over 140 studies revealed a robust association between ASM-induced changes and the onset of bleeding disorders via several different mechanisms. Polytherapy, the use of multiple ASMs, also emerged as a significant risk factor for the development of coagulopathies. This review highlights the potential link between ASMs and bleeding disorders, emphasizing the importance of considering this risk during treatment planning. By understanding these associations, healthcare providers can optimize patient outcomes and minimize bleeding risks. Additionally, this review identifies the need for further research to bridge current knowledge gaps in clinical pharmacology related to ASMs and bleeding disorders.

Introduction: This study aimed to investigate the association between the 2023 Beers criteria for inappropriate prescribing and different health outcomes among community-dwelling older individuals after a 1-year follow-up period and to assess the use and factors associated with inappropriate prescribing.

Methods: This longitudinal population study spanning from 2017 to 2018 included 490 community-dwelling older adults (≥60 years old) receiving care from family medicine teams in the city of São João del-Rei, Brazil. The 2023 Beers criteria was used to identify potentially inappropriate medications (PIMs). Community health workers carried out interviews assessing different health outcomes, such as cognition, sleep, mental health, quality of life, successful aging, and life satisfaction. Generalized estimating equations were used to evaluate whether the presence of PIMs was longitudinally associated with diverse outcomes following the 1-year follow-up period.

Results: A total of 255 (52%) of the participants used at least one PIM. The most common PIMs were benzodiazepines (36.5-38.3%), followed by proton pump inhibitors (16.2-18.4%) and sulfonylureas (9.8-10.6%). Some sociodemographic factors (e.g., marital status and race) and clinical factors (e.g., difficulties in activities of daily living and the number of diseases) were associated with the presence and/or number of PIMs at baseline. In the longitudinal analysis, the presence of PIMs exhibited associations with a spectrum of outcomes observed after a 1-year follow-up period. These outcomes included diminished physical quality of life (B = -0.21; p = 0.030), disrupted sleep patterns (B = 1.14; p < 0.001), compromised mental health-depression (B = 1.04; p = 0.041), stress (B = 2.00; p = 0.001), and anxiety (B = 1.26; p = 0.004), successful aging (B = -1.92; p = 0.033), and satisfaction with life (B = -0.77; p = 0.013).

Conclusion: The use of at least one PIM, according to the 2023 Beers criteria, was high and associated with worse health outcomes. This underscores the imperative for healthcare professionals to exercise caution when prescribing medications to older patients.

Background: The increasing demand for orphan drugs and the financial challenges associated with their reimbursement highlights the need to understand the dynamics between expected and actual pharmaceutical expenditures, particularly in the context of pricing and reimbursement negotiations.

Objective: The study aims to identify the potential determinants of the difference in expected pharmaceutical spending after negotiation and the actual expenditure incurred (ΔS), as well as the difference in expected pharmaceutical spending before and after the price and reimbursement negotiation process (ΔSn) for rare disease drugs in Italy.

Methods: The analysis focused on orphan drugs authorised by European Medicines Agency, with reimbursement applications to the Italian Medicines Agency from January 2013 to January 2019. Expected post-negotiation spending was estimated by applying negotiated discounts and financial-based market entry agreements to the expected pharmaceutical expenditure. The actual expenditure was approximated through company turnovers. Beta regression models were applied to identify potential determinants of ΔS and ΔSn.

Results: The study analysed 52 reimbursed orphan drugs, with 41 (78.8%) with a single indication, 25 (48.1%) antineoplastics and immunomodulators and 18 (34.6%) conditionally/fully innovative. The median expenditure in the first 3 years post-commercialisation was 7.6% lower than expected post-negotiation. The reduction was less pronounced for innovative drugs (p = 0.011), drugs with a prices and reimbursement procedure in the subsequent 3 years (p = 0.007) and those with multiple indications (p = 0.021). Payment-by-result was the only significant variable associated with the expected spending ratio before and after negotiation (p = 0.002).

Conclusion: The actual expenditure for orphan drugs aligns with the expected post-negotiation. Yet, innovative orphan drugs exhibit a higher actual expenditure than estimated, suggesting the market values their added therapeutic value or the actual therapeutic need they meet, and configuring innovativeness status as the main determinant of the orphan drugs financial impact in the multiple regression analysis.

Background: In October 2016, precautions of the package inserts for ethical drugs containing statins were revised for immune-mediated necrotizing myopathy (IMNM).

Objective: Our objective was to assess the trend in statin-associated IMNM reported before and after the release of the revised precautions in Japan.

Methods: We investigated the number of case reports and estimated annual incidence rate of statin-associated IMNM using the Japanese Adverse Drug Event Report and Japan Medical Data Center (JMDC) databases, respectively. To identify IMNM case reports, we used the preferred term "immune-mediated myositis" (MedDRA version 27.1).

Results: We identified 172 statin-associated IMNMs in 145 case reports of patients between 1 April 2004 and 31 March 2023. The most common suspected statin administered to the patients was rosuvastatin (34.3%), followed by pitavastatin (25.0%) and atorvastatin (22.1%). No statin-associated IMNM was reported in patients who were treated with combination agents containing statins. The number of reported statin-associated IMNMs increased from 3 in 2015 to a peak of 51 in 2019, after which it was 22 (2020), 17 (2021), and 21 (2022) in the following years. The estimated annual incidence rate did not differ with statins, it rarely exceeded 5 per 1,000,000 patients.

Conclusions: There was an increasing trend in the number of statin-associated IMNM after the revised precautions of package inserts for statins were released.

Background: Paediatric patients are prone to medication errors, but an in-depth understanding of errors involving high-alert medications remains limited.

Objective: We aimed to investigate incident reports involving high-alert medications to describe medication errors, error chains and stages of the medication management and use process where the errors occur in paediatric hospitals.

Methods: A retrospective document analysis of self-reported medication safety incidents in a paediatric university hospital in 2018-20. The incident reports involving high-alert medications were investigated using an inductive qualitative content analysis and quantified (frequencies and percentages). A systems approach to medication risk management based on the Theory of Human Error was applied.

Results: Altogether, 560 medication errors were identified within the study sample (n = 426 incident reports). Most medication errors were associated with administration (43.1 %, n = 241/560) and prescribing (25.2 %, n = 141/560). Error chains involving two to four medication errors in one or more stages of the medication management and use process were present in 26.1% (n = 111/426) of reports, most of which originated from prescribing (62.2%; n = 69/111). The medication errors (n = 560) were classified into 14 main categories, the most common of which were wrong dose (13.9%; n = 78/560), omission of a drug (12.9%; n = 72/560) and documentation errors (10.0%; n = 56).

Conclusions: Paediatric medication error chains often start from prescribing and pass through the medication management and use process. Systemic defences are especially needed for manual tasks leading to wrong doses, drug omission and documentation errors. Intravenous medications and chemotherapeutic agents, optimising drug formularies and handling, and high-alert drug use at home require further actions in paediatric medication risk management.

Background and objective: Performing lipid testing after statin initiation is recommended to monitor response. Inadequate response may indicate non-adherence, which is associated with an increased risk of cardiovascular events and increased costs. Group-based trajectory modeling is an approach to establish probabilistic developmental trajectories of adherence, differentiating individuals by their distinct longitudinal medication-taking behaviors. We examined whether lipid testing is associated with distinct trajectories of statin adherence among individuals enrolled in a Medicare fee-for-service plan in the USA.

Methods: A retrospective cohort study was conducted using the Centers for Medicare & Medicaid Chronic Condition Warehouse 5% sample of Medicare fee-for-service data between 2006 and 2015. Statin use and lipid testing were identified using claims data. The proportion of days covered was calculated for each 30 days after the index date, which was used to estimate the probability of belonging to each potential adherence trajectory.

Results: In a cohort of 138,101 statin initiators, four statin adherence trajectory groups were identified. The four groups were differentiated as "rapid decline" (21.53%), "gradual decline" (10.25%), "decline first then improve later" (26.47%), and "high adherence" (41.75%). Compared with "high adherence," initiators who had lipid tests within 360 days after statin initiation were less likely to fall into "rapid decline" (adjusted odds ratio: 0.661; 95% confidence interval 0.641-0.683), "gradual decline" (adjusted odds ratio: 0.834; 95% confidence interval 0.801-0.868), and "decline first then improve later" groups (adjusted odds ratio: 0.936; 95% confidence interval 0.910-0.962).

Conclusions: Lipid testing is positively associated with greater use of statin medication across different adherence trajectories in the present study.