Advances in Therapy最新文献

Introduction

Tegoprazan is a potassium-competitive acid blocker, and its systemic exposure is presumably affected by hepatic clearance and bioavailability. This study aimed to investigate the effect of hepatic impairment (HI) on the safety and pharmacokinetics of tegoprazan and metabolite.

Methods

An open-label, multicenter, parallel-group study was conducted in patients with mild (n = 8), moderate (n = 8) and severe (n = 1) HI according to the Child–Pugh classification as well as controls. Healthy subjects (n = 8) were matched to patients with the moderate category based on age, body mass index and sex. Blood and urine samples were obtained to evaluate the concentrations of tegoprazan and metabolite (M1) until 48 h after a single oral administration of 50 mg of tegoprazan.

Results

The geometric mean ratio with a 90% confidence interval of maximum plasma concentration and area under the plasma concentration–time curve for tegoprazan in patients with impaired hepatic function compared to controls were 0.8228 (0.4997–1.3550) and 1.2264 (0.7447–2.0197) in the mild category, 1.0332 (0.6274–1.7015) and 1.7676 (1.0733–2.9109) in the moderate category, and 1.0699 (0.3713–3.0823) and 1.9567 (0.6792–5.6377) in the severe category. The half-life, apparent clearance, renal clearance, and fraction unbound to plasma protein were comparable across study groups. The plasma concentration of M1 increased and decreased faster in the normal group. Tegoprazan was generally well tolerated in patients with HI.

Conclusions

Systemic exposure to tegoprazan tended to be increased in subjects with HI. The difference between patients with mild HI and the controls was deemed not to require dose adjustment for tegoprazan.

Clinical Trial Registration

ClinicalTrials.gov identifiers: NCT04494269 (31 Jul 2020).

Introduction

This study aimed to demonstrate the interchangeability of biosimilar CT-P17 and European Union reference adalimumab (EU-adalimumab) in a repeated-switch scenario.

Methods

In this ongoing, randomized, double-blind, active-controlled, phase 3 study, adults with moderate-to-severe plaque psoriasis received 80 mg EU-adalimumab on day 1, then 40 mg 1 week later and every other week until week 11. At week 13, patients were randomized (1:1, via an interactive web response system) to continue EU-adalimumab (“continuous” group) or undergo repeated switches between CT-P17 and EU-adalimumab (“switching” group). Dosing was via subcutaneous administration. The primary endpoints were area under the concentration–time curve and maximum serum concentration between weeks 25 and 27 (AUC_tau,W25–27 and C_max,W25–27, respectively). Secondary endpoints comprised additional pharmacokinetic (PK) parameters, efficacy, safety, and immunogenicity. Week 27 findings are presented.

Results

The first patient provided signed informed consent on November 7, 2022. Week 27 visits were completed by August 14, 2023. Of 367 patients enrolled, 346 were randomized (switching group, n = 172; continuous group, n = 174). The ratios of least squares means between groups and associated 90% confidence intervals (CIs) for AUC_tau,W25–27 and C_max,W25–27 were 99.45% (94.11–105.08%) and 100.45% (95.03–106.17%), respectively. For both endpoints, 90% CIs fell within the predefined equivalence margin of 80–125% and criteria were greater than calculated t values, satisfying bioequivalence. Additional PK endpoints and efficacy, safety, and immunogenicity findings were similar between groups. Safety profiles were in line with those previously reported.

Conclusions

Week 27 primary PK results demonstrated bioequivalence, and the overall study results supported the interchangeability of CT-P17 and EU-adalimumab.

Trial Registration

ClinicalTrials.gov, NCT05495568.

Introduction

Postoperative nausea and vomiting (PONV) is one of the most common postoperative complications, with particularly high rates in patients undergoing high-risk surgeries such as gynecologic laparoscopy. Although there are many pharmacological and non-pharmacological methods that can prevent PONV, the incidence remains high. This study assessed the effectiveness of a right stellate ganglion block (SGB) in preventing PONV in gynecological laparoscopy patients, while also exploring the potential mechanisms involved.

Methods

Two hundred patients were randomly assigned to either a right SGB under ultrasound guidance 30 min before anesthesia (SGB group) or no treatment (control group). The primary outcome was PONV incidence within 24 h post surgery. Secondary outcomes included nausea and vomiting severity, pain scores, postoperative flatus time, sleep quality, and satisfaction scores.

Results

The incidence of PONV in the SGB group was 38%, significantly lower than the 60% in the control group (P = 0.002). Severity of PONV was also notably reduced in the SGB group (P = 0.004). Resting pain scores in the SGB group at 6 h (0.0 [0.0, 1.0] vs. 0.0 [0.0, 2.0], P = 0.013), 12 h (0.0 [0.0, 1.0] vs. 0.0 [0.0, 2.0], P = 0.027), and 24 h (0.0 [0.0, 1.0] vs. 0.0 [0.0, 2.0], P = 0.011) were lower than in the control group. Post-activity pain scores at 6 h (2.0 [1.0, 3.0] vs. 3.0 [1.25, 4.0], P = 0.000), 12 h (2.0 [1.0, 3.0] vs. 3.0 [1.25, 4.0], P = 0.002), and 24 h (2.0 [1.0, 3.0] vs. 3.0 [2.0, 4.0], P = 0.001) were also lower. The time to first postoperative flatus was shorter in the SGB group (P = 0.033). Overall postoperative satisfaction (P = 0.002) and analgesia satisfaction (P = 0.002) were higher, and sleep quality was improved (P = 0.046).

Conclusion

A right stellate ganglion block reduces PONV, pain, and postoperative flatus time, and improves sleep quality and satisfaction in gynecological laparoscopy patients, proving it to be a safe and effective method.

Trial Registration: NCT06426186.

Introduction

This study aims to assess the cost-effectiveness of the fall 2023 COVID-19 mRNA XBB.1.5 vaccination campaign in the Netherlands, comparing the XBB1.5 updated mRNA-1273.222 with the XBB1.5 updated BNT162b2 vaccine.

Methods

A 1-year decision tree-based cost-effectiveness model was developed, considering three scenarios: no fall 2023 vaccination, BNT162b2 vaccination, and mRNA-1273 vaccination in the COVID-19 high-risk population in the Netherlands. The high-risk population includes everyone of 60 and older, and younger adults at high risk as identified by the Dutch Health Council. Costs were included from a societal perspective and the modelled period started in October 2023 and ended in September 2024, including life years lost with a lifetime horizon. Sensitivity and scenario analyses were conducted to evaluate model robustness.

Results

In the base case, mRNA-1273 demonstrated substantial benefits over BNT162b2, potentially averting 20,629 symptomatic cases, 924 hospitalizations (including 32 intensive care unit admissions), 207 deaths, and 2124 post-COVID cases. Societal cost savings were €12.9 million (excluding vaccination costs), with 1506 quality-adjusted life years (QALYs) gained. The break-even incremental price of mRNA-1273 compared to BNT162b2 was €16.72 or €34.32 considering a willingness to pay threshold (WTP) of 20,000 or 50,000 euro per QALY gained.

Conclusion

This study provides a comprehensive cost-effectiveness analysis supporting the adoption of the mRNA-1273 vaccine in the national immunization program in the Netherlands, provided that the Dutch government negotiates a vaccine price that is at most €34.32 per dose higher than BNT162b2. Despite limitations, the findings emphasize the substantial health and economic benefits of mRNA-1273 over BNT162b2 in the high-risk population.

Introduction

This article describes the study rationale and design of the real-world multicenter registry study iCaReMe China.

Methods

iCaReMe China is a prospective, multicentric, observational registry study aiming to understand the real-world characteristics of patients with type 2 diabetes (T2D) and/or hypertension (HTN) [combined chronic kidney disease (CKD)] and/or heart failure (HF) and/or CKD, which may provide some evidence for improving quality of care and outcomes of T2D and/or HTN and/or HF and/or CKD in China. A total of approximately 19,000 subjects will be recruited from 110 participating sites in China. Patients will be enrolled in four disease cohorts based on the primary disease conditions. The primary outcome is to describe the sociodemographic, clinical characteristics, disease management patterns, healthcare resource utilization, and clinical outcomes.

Conclusion

iCaReMe China aims to describe the real-world characteristics and treatment patterns of patient with T2D and/or HTN (combined CKD) and/or HF and/or CKD. The data from this prospective registry study will facilitate a better understanding of management strategies, the variations across and within different regions, and associated patient outcomes in China.

Trial Registration Number

ChiCTR2300073764.

Introduction

Disrupted linkage to care is a major barrier to hepatitis C virus (HCV) elimination leading to high attrition rates. This study aimed to describe (1) flow through the HCV care-cascade (2009–2020), and (2) monthly patterns in HCV care during the coronavirus disease 2019 (COVID-19) pandemic (2020) in Israel.

Methods

Data were obtained from Maccabi Healthcare Services, a 2.6-million-member healthcare provider in Israel. Flow through the HCV care-cascade in 2009–2020 was described from individuals' first positive HCV antibody (Ab+) test to sustained virological response (SVR), and monthly data were obtained on individuals newly attaining a given stage in the HCV care-cascade in 2020.

Results

Among 2809 new patients who were Ab+, 2651 (94.4%) had an HCV polymerase chain reaction (PCR) test, and 1417 (50.4%) were PCR+ during the study. Median time from Ab+ to PCR+ was 3.9 years, with 39.7% PCR+ within 12 months. Median time from PCR+ to HCV treatment was 3.3 years, with 639 (55.5%) of patients who were PCR+ purchasing direct-acting anti-viral agents (DAAs), and 413/416 patients attained SVR. A significant reduction was observed in the time from first HCV detection (Ab+) to HCV confirmation (PCR+) and from PCR+ test to HCV treatment purchase in the pre-DAA era compared to the post-DAA. Monthly data during 2020 (Part B) indicates a decline in the numbers of patients receiving HCV care during the first pandemic-related closure.

Conclusion

Real-world data from a nationally representative healthcare provider database suggest that HCV linkage to care improved over time alongside increased access to DAAs, despite observed declines in access to care in 2020.

Sinonasal tumors with orbital involvement present significant management challenges due to the complex anatomy of the orbital and sinonasal complex and the potential for severe tumor- and treatment-related morbidities. This comprehensive review examines evidence-based decision-making guidelines in the context of treating sinonasal malignancies involving the orbit. We evaluate pre-treatment assessment strategies, discuss the indications for orbital preservation versus its exenteration, explore the role of neo-adjuvant therapies, and analyze reconstruction techniques with ensuing rehabilitation approaches and quality of life. Our review underscores the need for a patient-centered multidisciplinary approach that optimizes treatment outcomes and quality of life for patients suffering from such advanced sinonasal malignancies with orbital involvement.

Introduction

Patient adherence to regular controller medication is critical for improving clinical outcomes in asthma, which is consistently associated with underlying pathophysiological inflammation. This survey aimed to identify types of treatment nonadherence and associated factors, including patient characteristics that predict poor adherence, in patients with asthma.

Methods

This cross-sectional online survey involved patients with asthma and physicians managing such patients from Southeast Asia (Indonesia, Malaysia, Philippines, Thailand and Vietnam) and the Middle East (Saudi Arabia and United Arab Emirates) included in the Asthma Patients’ and Physicians’ Perspectives on the Burden and Management of Asthma (APPaRENT) 3 study. Patients and physicians shared their attitudes and beliefs regarding treatment and adherence in asthma management.

Results

Most patients (82%, 1108/1354) reported having ever received treatment with daily controller inhalers, whereas 38% used inhaled relievers at least once daily for symptomatic relief. Among those prescribed maintenance and reliever therapy, 93% were prescribed a separate inhaled reliever, with significant variation by country (P < 0.01). Erratic nonadherence (primary definition) was exhibited by 55% (462/845) of patients including those who reported at least sometimes forgetting inhaler use, with its prevalence increasing with worsening asthma severity. Nonerratic nonadherence was exhibited by 49% (415/847) of patients including those who reported using controller inhalers less than once daily. Physicians reported that 73% of patients adhered to the prescribed regular medication. Regression analysis examining both erratic (primary definition) and nonerratic nonadherence revealed that current inhaled reliever used was the only significant predictor of poor adherence (P = 0.04). Sensitivity analyses revealed that the predictors of poor adherence to controller inhaler varied depending on the definition of nonadherence employed in the study.

Conclusion

This study revealed high rates of erratic and nonerratic nonadherence to regular controller inhalers in patients with asthma as well as discordance between adherence rates reported by patients and physicians.