Drugs - Real World Outcomes最新文献

Background: Alirocumab is a fully human monoclonal antibody to proprotein convertase subtilisin kexin type 9 used for the reduction of low-density lipoprotein cholesterol (LDL-C) in high-risk patients not reaching their LDL-C target. Recently, a 2-mL prefilled autoinjector has been developed to support the monthly 300-mg dosing regimen with a single-injection administration.

Methods and objectives: Monthly application of 300 mg AlirRocumab (Praluent^®) using the 2-mL SYDNEY Device (MARS) is a non-interventional, open, prospective, multi-center cohort study conducted in Germany between 2021 and 2023 with an observational period of 12 weeks. Patients included had primary hypercholesterolemia (heterozygous familial or non-familial) or mixed dyslipidemia and confirmed vascular disease and other risk factors or confirmed familial heterozygous hypercholesterolemia. Primary objectives were to assess the effectiveness of the 2-mL SYDNEY autoinjector measured by the lipid-lowering effect of alirocumab and to document therapy satisfaction, patient adherence, and persistence. Secondary objectives were to assess safety (adverse events) and tolerability.

Results: A total of 146 patients were analyzed: 110 (75.3%) patients were proprotein convertase subtilisin kexin type 9 inhibitor naïve and 36 (24.7%) were pre-treated with a proprotein convertase subtilisin kexin type 9 inhibitor. Patient mean age was 65.6 years with a preponderance of male gender (59.6%). At 12 weeks, the LDL-C value had decreased by a median of 59.5 mg/dL (1.5 mmol/L) in naïve patients (median relative decrease: - 52.0%). In the pre-treated group, the LDL-C value remained mainly unchanged (median slight numerical relative increase: 1.6%). Treatment satisfaction was rated similarly in both groups with most patients being satisfied/very satisfied and rating the injection as effective, safe, and easy to handle. Twenty-three adverse events in 13 patients (8.0%) were documented. Three patients experienced one serious adverse event each; for five patients, an adverse drug reaction was observed, although none was serious. The occurrence of adverse events was similar in both groups.

Conclusions: Alirocumab 300 mg administered with the 2-mL SYDNEY autoinjector was safe and effective in lowering LDL-C after 12 weeks in a routine clinical setting in Germany. The treatment schedule was perceived to be beneficial with excellent device acceptance and satisfaction, potentially increasing patient adherence.

Clinical trial registration: Clinicaltrials.gov: NCT05129241.

Background and objectives: Accumulating pediatric efficacy and safety data on drug use is inherently challenging yet essential. This study aimed to analyze the frequency and compute the odds of pediatric drug-associated liver injury across age groups (early childhood, middle childhood, and adolescence) and therapeutic categories using adverse drug reactions (ADRs) reporting data spanning nearly two decades.

Methods: We analyzed the reports of suspected ADRs occurring in children and adolescents in the Taiwan National Adverse Drug Reaction Reporting System during the period from May 1998 until July 2017. Standardized Medical Dictionary for Regulatory Activities Queries were utilized to identify suspected hepatic ADRs. Outcome patterns across age groups were compared using the chi-squared test, and disproportionality analysis was employed to calculate reporting odds ratios (RORs) of hepatic versus nonhepatic reports.

Results: Among 16,673 reports, 484 (2.9%) were identified as suspected hepatic ADRs, involving 193 distinct drugs. The mean age of affected individuals was 8.2 years. Outcome types in adolescents were predominantly serious (91.8%). Antibacterials for systemic use (18.8%) and antiepileptics (8.7%) were the most frequently implicated therapeutic categories. Drugs with high ADR occurrence rates and significant RORs included oxacillin (5.2%; ROR: 12.07), methotrexate (4.1%; ROR: 9.07), and phenobarbital (2.7%; ROR: 5.04). Some medications exhibited higher ratios of used-versus-recommended doses, suggesting inappropriate dosing.

Conclusions: Pediatric drug-associated liver injury was not uncommon and may result in serious outcomes. This study underscores the need for heightened vigilance in administering certain high-risk drugs and attentiveness in proper dosing for children, including adolescents.

Background: The combination of regorafenib and immune checkpoint inhibitor (ICI) has been the most popular second-line systemic therapy for advanced hepatocellular carcinoma (HCC). However, considering the good anti-tumor performance of lenvatinib, combined immunotherapy on the basis of lenvatinib after first-line lenvatinib failure is also popular in clinical practice. This study aimed to compare the efficacy and safety of regorafenib plus ICI (TACE-R-I) versus lenvatinib plus ICI (TACE-L-I) in patients with advanced HCC after lenvatinib failure.

Methods: In this single-center retrospective study, 164 patients with advanced HCC were enrolled from January 2019 to March 2024 in China. All patients were aged ≥ 18 years, clinically or pathologically diagnosed with HCC. All patients received trans-arterial chemoembolization (TACE) as local treatment. Overall survival (OS), progression-free survival (PFS), and treatment-related adverse events (TRAEs) were compared between groups. The Cox regression model was used to analyze the factors associated with OS and PFS.

Results: We compared 77 patients from each group after propensity score matching (PSM). There was no significant difference in the OS (p = 0.255) or PFS (p = 0.387) between groups. However, in the subgroup (distant metastases, Barcelona Clinic Liver Cancer (BCLC) stage C or tumor thrombus), the TACE-R-I group showed better survival benefit than the TACE-L-I group. The multivariable Cox regression model suggested that BCLC stage and alpha-fetoprotein (AFP) were independently associated with OS. Distant metastases, tumor thrombus and Child-Pugh were independent associated factors for PFS (p < 0.05). The frequency of grade ≥ 3 TRAEs was not significantly different between groups (p ≥ 0.05).

Conclusion: Our study demonstrated that in patients with greater tumor burden, the TACE-R-I group showed better OS and PFS benefits than the TACE-L-I group. However, in the overall population of HCC patients, there was no significant difference in efficacy and safety between the groups.

Background: Studies on medicinal cannabis (MC) have primarily investigated effects on diseases and symptoms, while there is only sparse knowledge on patients' health-related quality of life. Our aim was, firstly, to compare the health-related quality of life of patients (MC users and non-users) within four specified diagnostic indications (multiple sclerosis, paraplegia, neuropathy, and nausea and vomiting after chemotherapy) with that of patients with other diagnostic indications (MC users only) and the adult population (non-users only). Secondly, we estimate the associations between use of MC and health-related quality of life for patients in the four specified diagnostic indications.

Methods: We collected data on quality-adjusted life years (QALYs), using EQ-5D-3L, and patients' self-reported use of MC in a Danish nationwide online survey distributed to 23,846 patients in October 2020. We compared QALY scores of all groups using a two-tailed t-test, listed QALY scores of MC users versus non-users, and investigated associations between QALY score and MC use using unadjusted and adjusted linear regression analyses. Significance level was set to p-value < 0.05.

Results: A total of 9265 patients took part in the survey. All diagnostic indications had a statistically significant lower QALY score than the adult population (0.87). Paraplegia patients had the lowest QALY score, being 0.36 lower, followed by other diagnostic indication (- 0.34), multiple sclerosis (- 0.20), neuropathy (- 0.13), and nausea and vomiting after chemotherapy (- 0.06). MC users had a statistically significant lower QALY score than non-users (0.44 vs 0.74). Users redeeming 1-6 and ≥ 7 MC prescriptions (except for paraplegia patients) had a statistically significant lower QALY score than non-users, ranging between 0.11-0.24 and 0.26-0.32 lower than non-users, accordingly. Although, it should be noted that the number of users was small when stratifying by number of prescriptions.

Conclusion: Patients with either multiple sclerosis, paraplegia, neuropathy, or nausea and vomiting after chemotherapy had a significantly lower health-related quality of life than individuals from the adult population. Users of medicinal cannabis also had a significantly lower health-related quality of life compared with non-users, in all diagnostic indications.

Background and objective: The terminal complement inhibitor eculizumab is approved in the USA for the treatment of patients with acetylcholine receptor antibody-positive generalized myasthenia gravis (MG). The ELEVATE study aimed to examine clinical-practice outcome data on eculizumab effectiveness in US adults with MG (generalized or ocular). This paper reports the findings on MG exacerbations and crises and associated healthcare resource utilization, and the use of rescue therapy.

Methods: A retrospective chart review was conducted of US adults with MG who initiated eculizumab. Outcomes assessed for up to 2 years before and after eculizumab initiation included percentages and rates per patient per year (PPPY) of exacerbations and crises (the latter defined as intubation/impending intubation), healthcare resource utilization, and rescue therapy administration.

Results: A total of 119 patients diagnosed with MG were enrolled in the study; 92 patients had ≥ 3 months of data both before and during eculizumab therapy and were included in the analyses. The mean rate of MG exacerbations decreased from 0.385 PPPY before eculizumab initiation to 0.152 PPPY during eculizumab treatment (p = 0.0034); the mean rate of MG crises decreased from 0.411 to 0.056 PPPY (p = 0.0018). Rates of healthcare resource utilization and rescue therapy use also decreased significantly during eculizumab treatment.

Conclusions: This retrospective chart review analysis provides evidence for a beneficial impact of eculizumab treatment on the incidence of MG exacerbations and crises and associated healthcare resource utilization in clinical practice, and on rescue therapy use. These data further support the therapeutic benefits of eculizumab in patients with MG.

Background and objective: Accurate and robust adverse event (AE) data collection is crucial in cancer clinical trials to ensure participant safety. Frameworks have been developed to facilitate the collection of AE data and now the traditional workflows are facing renewal to include patient-reported data, improving completeness of AE data. We explored one of these workflows in a cancer clinical trial unit.

Methods: The study was a single-site study conducted at a tertiary hospital located in Australia. Patients consenting to a clinical trial were eligible for inclusion in this study. Participants used an electronic platform-My Health My Way (MHMW)-to report their symptomatic data weekly for 24 weeks. A symptom list was included within the platform, along with a free text field. Data reported via the platform was compared with data recorded in the patient's medical chart. Time taken to compile data from each source was recorded, along with missing data points. Agreement between patient-reported data and data recorded in the medical notes was assessed using Kappa and Gwet's AC₁; time taken to compile data and missing data points were assessed using a Wilcoxon signed rank test.

Results: Low agreement was found between patient- and clinician-reported data (- 0.482 and - 0.159 by Kappa and Gwet's AC₁ respectively). Only 127 (30%) of the total 428 AEs were reported by both MHMW and medical notes. Patients reported higher rates of symptoms from the symptom list, while clinicians reported higher rates of symptoms outside of the symptom list. Time taken to compile the data from MHMW was significantly less than that taken to review medical notes (2.19 min versus 5.73 min respectively; P <  0.001). There were significantly less missing data points from the MHMW data compared with the medical notes (1.4 versus 7.8; P < 0.001).

Conclusions: This study confirms previous reports that patient- and clinician-reported adverse event data show low agreement. This study also shows that clinical trial sites could significantly reduce the work performed by research staff in the collection of adverse event data by implementing an electronic, patient-reported platform.

Introduction: The association between omeprazole and hypertension is poorly documented. The summary of product characteristics of omeprazole approved by major regulators did not mention hypertension as an adverse drug event. Triggered by a locally reported case, this study was conducted to assess the possible causal relationship between omeprazole and hypertension.

Methods: Globally reported cases of hypertension following use of omeprazole submitted to the World Health Organization global database, VigiBase, were retrieved on 5 March 2024 and analyzed descriptively. Besides this, a literature search was made to identify preclinical, clinical, and epidemiological information on the association between omeprazole and hypertension or increased blood pressure using different data sources. Relevant information, gathered from different data sources, was finally systematically organized into an Austin Bradford-Hill causality assessment framework to assess the causal relationship between omeprazole and hypertension.

Results: VigiBase indicated a total of 1043 cases of hypertension related to omeprazole from 36 different countries. In the global database, a statistical signal was triggered (IC₀₂₅: 0.12) on association of omeprazole and hypertension. From the 1043 cases, 65.0% and 10.6% were reported as 'serious' and 'fatal', respectively. Hypertension resolved following withdrawal of omeprazole in 85 cases and recurred after re-introduction of the suspect drug in 14 cases. In 225 cases, omeprazole was the only suspected drug, while in 122 cases, omeprazole was the sole drug administered. When only these 122 cases were considered, 29 cases had positive dechallenge, four cases were with positive rechallenge and the median time-to-onset was 2 days. Literature search identified a possible biological mechanism and some experimental evidence that indicates omeprazole could possibly cause hypertension.

Conclusion: Currently available totality of evidence suggests there is a possible causal relationship between omeprazole and hypertension. Hence, it is recommended to monitor and report any incidence of hypertension related to omeprazole, and further epidemiological studies are recommended to corroborate the suggested causal association.

Introduction: The costs associated with proper disposal, management, and regulatory compliance of controlled substances in healthcare systems are substantial. In the context of the current opioid crisis, and given the high abuse potential of controlled substances, it is imperative that waste is minimized and waste procedures are followed to ensure safe disposal of controlled substances. This study aims to quantify the costs associated with fentanyl, hydromorphone, morphine, midazolam, and ketamine waste in intraoperative areas through a multi-site observational analysis.

Methods: The study used an observational design across various hospital procedural and post-procedural units in the Southwest Florida region of the United States. Automated and non-automated workflows for wasting controlled substances were compared. As with a previous study conducted by Hertig et al., waste was evaluated as (1) the quantity (mg/μg) of medication disposed defined as 'pharmaceutical waste' or 'product waste' (PW); and (2) workforce time associated with the waste disposal process defined as 'workforce time waste' (WTW). Secondary measures include workforce costs associated with the waste disposal process. The product waste analysis was conducted between October and December 2023. The workforce time waste analysis was examined over a 10-day period in January and February 2024. A yearly extrapolation model was applied to cost data.

Results: The findings revealed substantial costs linked to both PW and WTW, emphasizing the financial burden of controlled substance waste. Study data validated previous literature describing the extent of fentanyl, hydromorphone, and morphine waste while documenting significant amounts of midazolam and ketamine waste. The combined annual waste cost for the two study hospitals was estimated at US$56,557, with workforce time accounting for 36%-50% of this total cost.

Conclusion: This study provides vital insights into the financial and operational impact of medication waste in procedural and post-procedural areas, supporting ongoing efforts to minimize waste, ensuring the safe and effective use of controlled substances. Future research should explore the impact of medication waste across diverse healthcare settings and the cost implications associated with pharmacy professionals in the waste compliance process.