Advances in Therapy最新文献

Introduction

Subcutaneous (SC) formulations of oncology therapies could provide time-saving benefits for both patients and healthcare professionals (HCPs) compared with intravenous (IV) delivery. This prospective observational study, conducted alongside the MK-3475A-D77 phase 3, open-label randomized clinical trial, quantifies HCP and patient time with pembrolizumab SC versus pembrolizumab IV among patients with metastatic non-small cell lung cancer.

Methods

Seventeen sites across eight countries in Europe (n = 4), South America (n = 3), and Asia (n = 1) were enrolled. Primary endpoints were active HCP time; patient time in the treatment chair, treatment room, and healthcare facility; and consumables usage. Descriptive statistics included weighted mean (WM), and a linear mixed model (LMM) was employed to explore differences in time measures between pembrolizumab SC and pembrolizumab IV per visit.

Results

Overall, 212 observations were analyzed (153 SC and 59 IV). Total active HCP time was reduced by 45.6% with SC versus IV (WM, 14.0 vs 25.8 min); HCPs spent 44.3% less time on the drug preparation process with SC versus IV (WM, 5.1 vs 9.1 min) and 46.3% less time on the drug administration process with SC versus IV (WM, 8.9 vs 16.7 min). Patient chair time was reduced by 49.6% with SC versus IV (WM, 59.0 vs 117.2 min). Patients receiving SC spent less time in the treatment room than those receiving IV (WM, 66.7 vs 126.9 min; difference – 47.4%). Exploratory LMM showed considerable between-group differences for active HCP time and patient time in the treatment chair and treatment room.

Conclusion

Pembrolizumab SC substantially reduces active HCP time and patient chair time versus pembrolizumab IV. Time liberated for HCPs could be reallocated toward additional patient care activities, while optimized chair utilization could improve overall healthcare efficiency.

Introduction

This study aims to compare cardiovascular outcomes among patients who received long-acting beta-agonist (LABA) and long-acting muscarinic antagonist (LAMA) and thereby better inform the choice of pharmacotherapy prescription for patients with chronic obstructive pulmonary disease (COPD).

Method

A real-world territory-wide retrospective cohort study using electronic data patient databases in Hong Kong was conducted. Patients with COPD without cardiovascular disease who were new users of LABA or LAMA from public hospitals in Hong Kong between 2010 and 2019 were identified and were followed up for 3 years after treatment initiation. Incidences of cardiovascular events were compared. Propensity score matching was employed to match important patient characteristics and clinical features.

Results

After the propensity score matching, 5020 patients were included: 2510 treated with LABA and 2510 with LAMA. At 3-year follow-up, 19.6% of patients experienced cardiovascular events. LAMA treatment was associated with a higher incidence of cardiovascular events compared to LABA (20.2% vs 19.0%, adjusted hazard ratio [aHR] 1.14, p = 0.04). This difference was primarily driven by increased risks of new-onset atrial fibrillation (7.93% vs 6.53%, aHR 1.30, p = 0.01). Incidence rates were similar between groups for ventricular tachycardia and fibrillation (0.52% vs 0.80%, p = 0.32), acute coronary syndrome (4.06% vs 3.82%, p = 0.33), ischemic stroke (2.39% vs 2.59%, p = 0.98), and heart failure hospitalization (10.8% vs 9.84%, p = 0.05).

Conclusion

Patients with COPD treated with LAMA might have higher incidence of atrial fibrillation when compared with LABA but not other cardiovascular events.

Introduction

Congenital heart diseases (CHD) are the most common congenital anomalies, and fetal cardiac interventions (FCI) have been developed to improve perinatal outcomes. We aimed to conduct a systematic review and meta-analysis of observational studies to evaluate the effects of FCI on CHD.

Methods

We searched PubMed/Medline, Embase, and the Cochrane Central Register of Controlled Trials from inception to April 2025 without language restrictions. References of included studies and prior reviews were also screened. The protocol was registered in the International Prospective Register of Systematic Reviews (PROSPERO; ID CRD42024599628). Eligible studies included observational cohorts evaluating intrauterine procedures for CHD. Data were synthesized using random effects models in RStudio (version 4.2.2), and study quality was assessed with the Newcastle–Ottawa Quality Assessment Form for Cohort Studies (NOS).

Results

Twelve studies including 485 fetuses with CHD were analyzed. The pooled overall survival rate after fetal cardiac intervention was 57.4% (95% confidence interval [CI] 39.8–73.3), with survival ranging from 20.0% to 90.2% across studies. The pooled perinatal mortality rate was 31.5% (95% CI 21.0–44.2), with estimates ranging from 9.8% to 66.7%. Substantial heterogeneity was observed for both outcomes (I² > 75%).

Conclusion

FCI for CHD are associated with moderate overall survival but substantial perinatal mortality. Standardized protocols, refined patient selection, and multicenter collaboration are needed to improve outcomes and guide clinical decision-making.

Introduction

Recurrent respiratory tract infections (RRTIs) are common in childhood and impose substantial socioeconomic burden. β-Glucans, particularly pleuran from Pleurotus ostreatus, demonstrate immunomodulatory properties through the pathogen-associated molecular pattern receptor interactions. This study evaluated a novel chewable pleuran-based supplement with vitamin D and zinc for preventing respiratory infections in children with RRTIs.

Methods

This international, multicentre, randomised, double-blind, placebo-controlled trial enrolled 249 children with RRTIs from Slovakia, Czech Republic, and Serbia. Participants received either pleuran-based supplement (IMG® with vitamin D and zinc) or active placebo (vitamin D and zinc) for 3 months during respiratory infection season (October–March). Primary endpoint was total respiratory tract infections (RTIs). Secondary endpoints included RTI subtypes, RTI duration, missed school days, and safety evaluations.

Results

In total, 217 children completed the study (104 active, 113 placebo). The active group experienced significantly fewer total RTIs versus placebo (2.35 ± 1.25 vs. 2.77 ± 1.78; P = 0.042), representing 15.2% reduction over 3 months. Common cold episodes were reduced by 18.6% (1.53 ± 1.22 vs. 1.88 ± 1.25; P = 0.040). Effects were pronounced in children over 6 years (P = 0.026 for total RTIs; P = 0.005 for common cold) and evident after the first month (P = 0.037). Tonsillopharyngitis showed significant reductions in frequency (P = 0.003) and duration (P = 0.009). Post hoc analysis of children enrolled at respiratory season onset confirmed significant reductions in common cold frequency (P = 0.004) and duration (P = 0.023). The supplement demonstrated excellent tolerability with 98.7% compliance and only mild adverse events.

Conclusion

Chewable pleuran-based supplement with vitamin D and zinc significantly reduced respiratory tract infections in children with RRTIs, with rapid onset and favourable safety profile, demonstrating therapeutic potential in this vulnerable population.

Trial Registration

ClinicalTrials.gov ID NCT06974747.

Gastroenteropancreatic neuroendocrine tumors (GEP-NETs) comprise a heterogeneous group of clinically diverse tumors; their management is based on clinical characteristics. International guidelines recommend standard-dose somatostatin analogues (SSAs) as first-line treatment for advanced, low-grade G1 and “low” G2 NETs. No standard-of-care treatment is determined for “high” G2 and G3 NETs. Radioligand therapy (RLT) with [¹⁷⁷Lu]Lu-DOTA-TATE was authorized to treat well-differentiated (G1 and G2) unresectable or metastatic, somatostatin receptor (SSTR)-positive GEP-NETs, in progression after SSA. Recently published NETTER-2 is the first randomized clinical trial to demonstrate the efficacy and safety of [¹⁷⁷Lu]Lu-DOTA-TATE as first-line treatment in patients with newly diagnosed, advanced “high” G2 and G3 GEP-NETs. In February 2024, 13 scientific board members discussed RLT guidelines and treatment perspectives in patients with GEP-NETs based on NETTER-2 outcomes. In their opinion, NETTER-2 will impact first-line treatment choice in patients with G2 SSTR-positive GEP-NETs. RLT as first-line treatment could reduce tumor burden rather than maintain stable disease, except in patients who are highly symptomatic where chemotherapy should be considered. In patients with G3 SSTR-positive GEP-NETs, NETTER-2 strongly supports RLT as potential first-line treatment. RLT could also have a significant role in a perioperative setting for those cases with borderline resectable disease or advanced oligometastatic disease. The results of NETTER-2 confirm that therapy selection should be guided by symptoms, syndrome, and functional expression of SSTR within the tumor site(s) rather than GEP-NET histology and grading. Thus, the scientific board agreed that RLT should always be considered in SSTR-positive GEP-NETs. Graphical Abstract available for this article.

Graphical Abstract

Introduction

Patients with chronic kidney disease (CKD) and type 2 diabetes mellitus (T2DM) face high medical and economic burdens. However, information on healthcare utilization and medical expenditures for these patients in China is limited. This study aims to describe these aspects in a regional population in China.

Methods

Adult patients with CKD and T2DM from an electronic health record (EHR)-based longitudinal cohort study in Yinzhou, Ningbo, China were included between 2017 and 2020. Annual medical costs in Chinese yuan (CNY) and their equivalent in United States dollars (USD) and healthcare utilization (length of hospital stay, outpatient visits) were described by CKD stages. Two-part models estimated medical costs and healthcare utilization for each CKD stage.

Results

A total of 16,521 patients were included. The average total medical cost for all patients increased from 7087 (14,432) [mean (SD)] in 2017 to 10,901 (30,621) CNY in 2020. Medical costs across CKD stages increased in both outpatient visit expenses and hospitalization costs. In particular, hospitalization costs for patients with G3 increased from 3963 (12,497) to 9970 (39,513) CNY, and for G4 from 12,394 (24,571) to 19,421 (48,299) CNY. Overall, two-part model estimation results showed that outpatient visits increased from 11.8 (10.4) times in 2017 to 12.9 (11.1) in 2020, and length of stay increased from 3.4 (10.9) to 4.5 (16.7) days.

Conclusions

The study revealed that outpatient visits were main healthcare delivery method across CKD stages, with rising medical costs and healthcare utilization, especially hospitalization costs in G3 and G4. These findings highlight the need for efficient outpatient management and timely interventions in China.

Introduction

Success of medical therapy in glaucoma relies on a delicate yet difficult balance between efficacy, tolerability, and adherence. Preservative-free (PF) formulations enhance tolerability and adherence and, by reversing glaucoma therapy-related ocular surface disease, improve long-term efficacy and the success of medical therapy, impacting millions of patients worldwide. By increasing contact time and reducing the concentration of active ingredients gel-formulated eyedrops the aim is to optimize antiglaucoma therapy.

Methods

We review evidence for a well-established PF gel-formulated option, timolol 0.1%, and discuss the emerging potential and value of two novel PF gel-formulated agents: bimatoprost 0.01% and the fixed combination (FC) of bimatoprost 0.01%/timolol 0.1%.

Results

Cumulative evidence confirms PF gel-formulated timolol 0.1% once daily to be equivalent in efficacy to timolol 0.5% solution dosed twice daily, but safer. In a 3-month regulatory trial PF gel-formulated bimatoprost 0.01% demonstrated non-inferiority versus preserved bimatoprost 0.01% solution. More recently, a novel PF gel-formulated FC incorporated, for the first time, timolol 0.1% and bimatoprost 0.01%. By reducing the concentration of both active ingredients this FC aims to improve long-term tolerability and allow safer systemic delivery of timolol. Preliminary phase II controlled evidence demonstrated similar diurnal efficacy between the new FC and the popular bimatoprost 0.03%/timolol 0.5% FC. We hypothesize that the wider adoption of PF gel-formulated agents will enhance glaucoma treatment options. Finally, we identify areas of unmet need that warrant further investigation.

Conclusions

Overall, PF gel-formulated agents appear to be safer than and as effective as equivalent preserved antiglaucoma medications.

Hereditary angioedema (HAE) is a rare genetic disorder characterized by unpredictable and potentially life-threatening episodes of swelling, driven primarily by excessive bradykinin production. These episodes commonly involve the skin, gastrointestinal tract, and upper airway, significantly impacting patients’ quality of life. Recent advances in understanding the underlying pathophysiology of HAE have transformed clinical care, enabling the development of highly targeted treatments that disrupt critical steps within the kallikrein–kinin pathway. Current on-demand therapies rapidly relieve acute symptoms, while contemporary prophylactic strategies have substantially reduced attack frequency and improved patient autonomy and health-related quality of life. Emerging therapies—including novel oral agents, monoclonal antibodies, RNA therapies, and pioneering gene editing approaches—continue to evolve, aiming to simplify treatment and further personalize care. These innovative treatments collectively strive to address remaining unmet needs, ensuring broader accessibility, convenience, and long-term sustainability of care for individuals living with HAE. This narrative review highlights the progression of therapeutic options in HAE, summarizing current advances and exploring future strategies toward personalized and patient-centered care.

Introduction

The combination of immunosuppressive therapy (IST) and pulmonary artery vasodilators has demonstrated potential effectiveness in treating pulmonary arterial hypertension (PAH) associated with connective tissue diseases (CTD-PAH) other than systemic sclerosis (SSc). However, large-scale studies of this topic are limited. This study aimed to evaluate the effectiveness of early IST in treating PAH in patients diagnosed with non-SSc CTD-PAH.

Methods

Clinical data for patients with non-SSc CTD-PAH were collected from the Japan Pulmonary Hypertension Registry spanning 2008–2021. Early IST was defined as the initiation or intensification of therapy within 3 months of PAH diagnosis.

Results

The study included 141 patients (mean age 51 ± 16.7 years; 95% female), with 57 receiving early IST, across 43 centers in Japan. The primary underlying diseases were systemic lupus erythematosus, mixed connective tissue disease, and Sjögren syndrome. At baseline, there were no significant differences in hemodynamics or PAH treatment regimens between the IST and non-IST groups. However, the IST group was notably younger, had higher plasma IgG levels, and maintained better renal function. The IST group showed significantly greater improvements in mean pulmonary artery pressure (mPAP) and pulmonary vascular resistance (PVR) over 12 months (p = 0.032 and p = 0.028), along with significant reductions in all-cause (p = 0.039) and PAH-related (p = 0.020) mortalities. No significant differences in deaths due to infections or malignancies were observed between groups.

Conclusion

Our data suggest that early initiation of IST may be associated with hemodynamic improvement; prospective confirmation in international cohorts is warranted.

Introduction

The EF-BI study, a nationwide observational and retrospective study conducted in France, found better insulin persistence, fewer insulin therapy-related acute hospitalizations, and lower healthcare costs in adults with Type 2 diabetes (T2D) who initiated treatment with insulin glargine 300 U/mL (Gla-300) compared to those who started on insulin glargine 100 U/mL (Gla-100) over a 3-year follow-up period. Given the heterogeneity of the T2D population, the benefits observed may vary according to individuals’ characteristics. A post hoc analysis of this study was conducted to verify whether these findings were consistent in all age groups, including the elderly population.

Methods

Using the French national health insurance information system, adults with T2D who initiated basal insulin therapy with Gla-300 or Gla-100 between January 1, 2016, and December 31, 2020, and had no prior insulin use in the previous 6 months, were selected. Covariate adjustment using a propensity score based on key individuals’ characteristics was applied to estimate outcomes and costs between the two basal insulins. Analyses were conducted using several age cut-offs (65, 75, and 80 years).

Results

Overall, 235,894 people with T2D were included: 175,537 initiated treatments with Gla-100 and 60,357 with Gla-300. Across both age groups (< 65 years or older), treatment with Gla-300 was associated with better persistence and a lower frequency of acute insulin-related events. Cost comparisons per individual treated over 3 years showed significant results favoring Gla-300:— €2,031 (− 7.3%, p < 0.0001) in the < 65 years group, and— €2,914 (− 7%, p < 0.0001) in the older group.

Conclusion

This EF-BI post hoc analysis found that Gla-300 was associated with lower overall costs, better persistence, and fewer insulin-related acute events compared to Gla-100 in several age subgroups in people with T2D in France. Further investigations are needed to confirm these results, including glycemic control and comparison with other second-generation basal insulins