Clinical Drug Investigation最新文献

Objective: The RENOTORCH trial found that toripalimab plus axitinib extended progression-free and overall survival in patients with advanced renal cell carcinoma (RCC), though its financial burden may limit widespread use. This study aimed to assess the cost-effectiveness of toripalimab plus axitinib compared with sunitinib monotherapy as a first-line therapy for patients with previously untreated or intermediate- or poor-risk advanced RCC from a US third-party payer perspective.

Methods: A three-state partitioned survival model (progression-free, progression, death) was utilized, with clinical outcomes obtained from the RENOTORCH trial. Progression-free survival (PFS) and overall survival (OS) were modeled using various parametric functions over a 5-year horizon, applying a 3% annual discount rate. Costs of treatments, administration, monitoring, and management of grade 3/4 adverse events (≥ 5% occurrence) were sourced from Micromedex® and Centers for Medicare & Medicaid Services (CMS) databases. Life years (LY), quality-adjusted life years (QALY), and incremental costs per LY and QALY were estimated. One-way and probabilistic sensitivity analyses were conducted. Subgroup analyses for intermediate- and poor-risk patients, as classified by the International Metastatic RCC Database Consortium (IMDC) criteria, were performed using similar methods.

Results: Toripalimab plus axitinib increased total costs by $332,359, gained 0.68 LY and 0.36 QALY compared with sunitinib, resulting in incremental costs of $489,747 per LY and $923,962 per QALY. One-way sensitivity analysis showed that the incremental cost per QALY was most sensitive to changes in toripalimab plus axitinib's cost. At a $150,000 willingness-to-pay threshold, probabilistic sensitivity analysis showed a nearly 0% probability of toripalimab plus axitinib being cost-effective. Similarly, toripalimab plus axitinib was still not cost-effective for intermediate- and poor-risk patients.

Conclusions: Compared with sunitinib monotherapy, our study suggested that toripalimab plus axitinib was not cost-effective for patients with advanced renal cell carcinoma from a US third-party payer perspective. Further analyses are warranted when more data are available. Despite benefits across different risk groups, toripalimab plus axitinib was not cost-effective for intermediate- and poor-risk patients.

Background: Patients with infective endocarditis can develop various renal diseases, including infective endocarditis-associated glomerulonephritis. Antibiotics are essential for eradicating the infection. However, the prognosis for renal function remains poor. This systematic review examines the role of immunosuppressants in managing infective endocarditis-associated glomerulonephritis (GN).

Methods: A comprehensive search was performed across four databases: PubMed, Scopus, MedLine, and Web of Science up to April 2024. We included studies that investigated patients with any type of GN due to infective endocarditis (IE) who were treated with immunosuppressants. Data extraction was conducted using a standardized sheet, and study quality was assessed using the Joanna Briggs Institute (JBI) critical appraisal tool.

Results: The review incorporated 55 studies encompassing 84 cases, 65 of whom were male. The median age was 46.5 years. A total of 30 cases required kidney replacement therapy. Following immunosuppressive therapy, clinical improvement of IE was observed in 54 cases, while 9 patients experienced worsening conditions, 3 patients had no clinical change, and data were unavailable in 18 cases. Renal outcomes showed improvement in 67 patients, with 9 cases showing worsening conditions, 3 patients showing no change, 3 experiencing partial or residual impairment, and renal outcome was unavailable in 2 cases. A total of ten patients died, primarily owing to sepsis or infection-related complications (five cases), congestive or global heart failure (three cases), and renal failure with associated metabolic complications (two cases). Additional treatments included plasma exchange, with nine cases receiving plasmapheresis/plasma exchange. Of these, eight patients showed marked renal function improvement, and one patient showed partial improvement. Three patients also received intravenous immunoglobulin.

Conclusions: Immunosuppressive therapy led to renal function improvement in the majority of cases, suggesting its potential benefit in managing infective endocarditis-associated glomerulonephritis. However, variability in response and significant mortality highlight the need for individualized treatment strategies and further research to optimize management.

Background and objective: Access to direct oral anticoagulants (DOACs) in sub-Saharan Africa is limited due to prohibitive upfront costs, making warfarin the standard of care for many patients, especially those relying on public-sector healthcare. This study evaluated the cost-effectiveness of using the DOAC, rivaroxaban, compared to warfarin for treating venous thromboembolism (VTE), a cardiovascular disorder caused by blood clots in the veins, in western Kenya.

Methods: We developed a discrete-time individual state-transition Markov model to simulate a VTE patient's quality-adjusted life-years (QALYs) and annual treatment costs under a rivaroxaban or warfarin therapy strategy. Transition state probabilities were derived from real-world event-rate data observed in patients treated with rivaroxaban (n = 160) or warfarin (n = 116) for VTE at Moi Teaching and Referral Hospital in western Kenya. Base-case parameter values were obtained from cohort event rates, local costs, and literature-derived utility values. Cost-effectiveness was assessed over a 1-year time horizon using an incremental cost-effectiveness ratio (ICER) threshold of (US)$6020.40 per QALY gained (equivalent to three times Kenya's 2021 per capita GDP). Deterministic and probabilistic sensitivity analyses were conducted to assess parameter and model uncertainty.

Results: After 12 months, total mean treatment costs per patient were $216.00 and $173.00 using warfarin and rivaroxaban, respectively. In the base-case analysis, rivaroxaban therapy resulted in an additional 0.023 QALYs per patient compared to warfarin, with an ICER of $- 1862.00 per QALY gained. Based on probabilistic sensitivity analysis with Monte Carlo simulation, when costs, utility values, and event rates were varied, rivaroxaban was cost-effective compared to warfarin in 84.1% of all simulations at a willingness-to-pay threshold of $6020.40 per QALY. One-way sensitivity analyses and scenario analyses were stable with rivaroxaban therapy, resulting in fewer costs and higher QALYs.

Conclusions: In this study, rivaroxaban is a clinically and economically superior alternative to warfarin. This research may catalyze further discussions with policymakers and industry partners to scale up the appropriate use of rivaroxaban in resource-constrained settings.

Background and objectives: Cannabinoid treatments are commonly used for sleep conditions, but the direct sedating effects of daytime treatment consumption and indirect effects on night-time sleep are unclear. This study measures the direct effects of low-dose cannabinoid treatments on daytime sleepiness and potential indirect night-time sleep effects in healthy adult, novice cannabis users.

Methods: Using a double-blind, randomised, placebo-controlled cross-over design, participants were orally administered a standardised dose of 1 mL oil containing THC:CBD ratios of either 1:1, 1:16 or a placebo over five weekly in-lab visits. Daytime sleepiness was measured at 40, 135 and 265 min post-dosing using the Karolinska Sleepiness Scale (KSS). Indirect night-time sleep effects on total sleep time (TST), sleep-onset latency (SOL), and number of awakenings after onset were measured using daily wrist-actigraphy and sleep-diary entries during the 7-day washout period between treatments.

Results: Final analyses (N = 20) showed subjective sleepiness (KSS score) significantly increased (mean difference = 1.9, SE 0.25) from 40 min to 265 min post-treatment (p < 0.001). No significant differences were observed between treatments for KSS. Indirect sleep measures (TST, SOL, number of awakenings) showed no differences between treatments or over time (all p > 0.05).

Conclusion: Daytime consumption of low-dose cannabinoid oils did not induce direct sleepiness or indirect night-time effects post-dosing among adults. Future studies would benefit from exploring pharmacokinetics and the possibility of treatment amplification of daytime fatigue, mood and cognitive changes to assist the development of therapeutic guidelines for safe daytime medical cannabis use.

Anctr trial registration number: ACTRN12622001539729, 13 December 2022, prospectively registered.

Background: Osteoarthritis affects the cartilage tissue lining the joint. Current management plans often require intra-articular injections to relieve symptoms. This approach is hindered by the difficulty in localising the drug released in the synovial fluid into the cartilage surrounding the affected joint. Drug delivery systems have been developed to support cartilage drug uptake, potentially reducing the number of injections required. We developed an approach to drug localisation that exploits the highly electrostatically charged nature of cartilage constituents through binding biologically active molecules to positively charged polymers, and demonstrated high efficacy and safety in ex vivo tests.

Objectives: We wanted to demonstrate the potential value of cartilage drug localisation technology beyond a clinical perspective, through health economic considerations and cost-effectiveness analysis, in order for these technologies to reach patients. We also conducted threshold analyses to determine, for different effectiveness levels of reducing injections, at what price the treatment will be cost-effective.

Methods: We conducted an early health economic analysis of our technology, developing a cost-effectiveness model with a Markov structure. The analyses were conducted from an NHS perspective and the model was also used to estimate potential cost-effectiveness depending on target product profiles. The health states quality of life values were derived for a UK population through EQ-5D questionnaires collected and analysed in a Bayesian framework.

Results: At the cost and effectiveness values set for the new treatment, it was cost-effective (increased costs of £16.28 and 0.001126 QALY per patient, resulting in an incremental cost-effectiveness ratios [ICER] of £14,459/QALY) but the results were highly uncertain (at a willingness-to-pay [WTP] of £20,000 and £30,000/QALY the probability of being cost-effective was 56.5% and 67.3%, respectively); while sensitivity analyses (one-way deterministic and probabilistic), within plausible ranges of model parameters, revealed that the efficacy of the technology in reducing intra-articular injections and its cost are the most influential parameters.

Conclusions: Clinical trials are needed to validate the in vivo drug delivery system efficacy, but our study suggests that the system is likely to be a cost-effective use of NHS resources, also improving healthcare providers capacity.