2025-09-02 於2025月09月02日

Monthly Mepolizumab Prevents Exacerbations among COPD Patients with Eosinophilic Phenotype

Date: May 1, 2025

Chronic Obstructive Lung Disease (COPD) is a progressive lung disease characterized by chronic bronchitis and/or emphysema, with an estimated 20 to 40% of patients presenting signs of eosinophilic inflammation. Alternations resulting from eosinophilic inflammation are possible to worsen existing COPD symptoms and leads to exacerbations requiring hospitalization. Mepolizumab, a humanized monoclonal antibody targeting interleukin-5, is thus considered as a potential treatment option for COPD patients with eosinophilic phenotype.

The multi-centre, double-blind, randomized and placebo-controlled MATINEE trial recruited 804 COPD patients with eosinophilic phenotype and had episode(s) of moderate or severe exacerbations 12 month before screening. Eligible participants were then randomly assigned in 1:1 ratio to receive either subcutaneous 100mg mepolizumab (n=403) or placebo (n=401) injection every 4 weeks as add-on to their ongoing triple inhaled therapy for up to 104 weeks. The primary end point was the annualized rate of moderate or severe COPD exacerbations. Time to the moderate or severe exacerbation and patient-reported outcome measures were regarded as secondary end points.

The annualized rate of moderate or severe exacerbations in the mepolizumab and placebo group were 0.80 and 1.01 events per year (rate ratio=0.79, 95% confidence interval [CI], 0.66-0.94; P=0.01) respectively. The Kaplan-Meier median time to the first moderate or severe exacerbation was 419 days (95% confidence interval [CI], 332-530 days) in the mepolizumab group, while the median time to first exacerbation was 321 days (95% confidence interval [CI], 262-396 days) in the placebo group. The incidence of adverse or serious adverse event during or after the treatment period was similar for both groups.

To conclude, monthly subcutaneous injections of mepolizumab helps to prevent moderate or severe exacerbations when added to background triple inhaled therapy among COPD patients with eosinophilic phenotype.

Source: www.nejm.org

Obicetrapib Lowers LDL-C and Improves Outcomes in High-Risk Cardiovascular Patients

Date: May 07, 2025

Obicetrapib is a highly selective cholesteryl ester transfer protein (CETP) inhibitor that have shown promising results in early trials to lower low-density lipoprotein (LDL) cholesterol levels and increase high-density lipoprotein (HDL) cholesterol levels. However, the full efficacy and safety profile of obicetrapib among patients at high risk for cardiovascular events is unknown.

In this multinational, randomized, placebo-controlled trial (BROADWAY), patients with heterozygous familial hypercholesterolemia or a history atherosclerotic cardiovascular disease (ASCVD) who were receiving maximum tolerated doses of statin therapy, with or without ezetimibe, bempedoic acid or PCSK9 inhibitors and were at high risk for cardiovascular events were recruited. Eligible patients were randomly assigned in a 2:1 ratio to receive oral obicetrapib (10mg) once daily or matching placebo for 365 days. The primary efficacy endpoint was the percent change in the LDL cholesterol level from baseline to day 84. 

A total of 2530 patients spanning 188 sites in China, Europe, Japan, and the United States, were randomly assigned to receive obicetrapib (n = 1686) or placebo (n = 844). The least-squares mean percent change from baseline to day 84 in the LDL cholesterol level was −29.9% (95% confidence interval [CI], −32.1 to −27.8) in the obicetrapib group, as compared with 2.7% (95% CI, −0.4 to 5.8) in the placebo group, for a between-group difference of −32.6 percentage points (95% CI, −35.8 to −29.5; P<0.001). The incidence of adverse events appeared to be similar in the two groups.

In conclusion, obicetrapib has demonstrated greater reduction in LDL cholesterol levels than placebo among patients with ASCVD or heterozygous familial hypercholesterolemia who were on maximum tolerated doses of lipid-lower therapy and were at high risk for cardiovascular events.

Source: www.nejm.org

Intravenous Tenecteplase Before Thrombectomy Shows Improved 90-day Functional Outcomes  

Date: May 21, 2025

In patients with acute ischemic stroke due to large vessel occlusion, administering thrombolysis prior to thrombectomy may enhance reperfusion outcomes. While alteplase remains the standard tissue plasminogen activator (tPA) for intravenous thrombolysis before thrombectomy, more studies suggest that tenecteplase offers significant time and cost advantages over alteplase.

A recent randomized, open-label trial conducted in China included patients who were eligible for thrombolysis and presented within 4.5 hours of symptom onset. Participants were assigned to receive either intravenous tenecteplase followed by thrombectomy or thrombectomy alone. The primary outcome measured was functional independence at 90 days, assessed using the modified Rankin scale (scores of 0 to 2, from a range of 0 to 6). Secondary outcomes focused on successful reperfusion rates and safety metrics, including symptomatic intracranial hemorrhage and mortality.

The trial enrolled 550 patients, with 278 assigned to the tenecteplase-thrombectomy group and 272 to the thrombectomy-alone group. 52.9% of patients in the tenecteplase group achieved functional independence at 90 days compared to 44.1% in the control group, indicating a statistically significant improvement (Unadjusted risk ratio, 1.20; 95% confidence interval, 1.01 to 1.43; P= 0.04). Successful reperfusion rates prior to thrombectomy were 6.1% in the tenecteplase group versus 1.1% in the control group, while post-thrombectomy rates were 91.4% and 94.1%, respectively. The incidence of symptomatic intracranial hemorrhage within 48 hours and death within 90 days did not differ significantly between the groups. 

In conclusion, the addition of intravenous tenecteplase to thrombectomy demonstrates significant improvement in functional independence of patients with acute ischemic stroke due to large vessel occlusion.

Source: www.nejm.org

Amendment to Dangerous Drugs Ordinance: Etomidate Analogues Classified as Dangerous Drugs

Date: July 16, 2025

On July 16th, The Hong Kong Drug Office announced that all analogues of etomidate—specifically isopropoxate, metomidate, and propoxate—along with six other drugs, will now be classified as dangerous drugs under Part 1 Schedule 1 of the Dangerous Drugs Ordinance (DDO). This update expands the previous legislation, which only included etomidate.

Etomidate, often referred to as the "space oil drug," began circulating among high-risk groups in 2024.  According to the Central Registry of Drug Abuse maintained by the Narcotics Division, there were 493 recorded "space oil drug" abusers from 2023 to May 31, 2025, with 356 of them being young people under 21. Etomidate is primarily used as a short-acting intravenous anesthetic for inducing anesthesia. However, misuse of etomidate and its analogues can lead to dependence and serious health issues, making them susceptible to criminal exploitation to evade legal consequences. Overdose symptoms may include tremors, hallucinations, irreversible nerve damage, and respiratory arrest.

Recent scientific analysis has indicated that certain analogues of etomidate, which was yet classified as dangerous drugs, may potentially be abused. In an proactive measure against the misuse of etomidate, the DDO has now included its analogues and established a general definition for them. This aims to combat the possession and trafficking of these substances by prohibiting public consumption and use, thereby enhancing public safety and health.

Source: www.info.gov.hk

Tarlatamab Prolongs Overall Survival in Small-Cell Lung Cancer Patients Resistant to Platinum-Based Chemotherapy

Date: July 24, 2025

Small-cell lung cancer is an aggressive cancer with rapid rates of metastasis and recurrence. Although most patients respond to first-line platinum-based chemotherapy, etoposide and programmed death ligand 1 (PD-L1) inhibitor therapy recommended by clinical guidelines, poor prognosis is often noted in small-cell lung cancer patients with progression during or after initial platinum-based chemotherapy. Tarlatamab is a bispecific T-cell engager immunotherapeutic agent targeting delta-like ligand 3 on small-cell lung cancer cells to trigger tumour-cell lysis.

The multinational, open-label and randomized phase 3 trial recruited patients with small-cell lung cancer that had progressed during or after first-line platinum-based chemotherapy and with an Eastern Cooperative Oncology Group performance-status score of 0 or 1. A total of 509 patients were then randomly assigned in 1:1 ratio to receive intravenous tarlatamab (n=254) or second-line chemotherapy (n=255) based on pre-defined treatment protocol as active control. Choices of second-line chemotherapy include topotecan, lurbinectedin or amrubicin. The primary end point was overall survival defined as the time from randomization to death from any cause.

As of the data cut-off date in January 2025, the median overall survival was 13.6 months in the tarlatamab group and 8.3 months in the control group (Stratified hazard ratio for death=0.60, 95% confidence interval [CI], 0.47-0.77; P<0.001). The estimated restricted mean progression-free survival at 12 months was 5.3 months in the tarlatamab group and 4.3 months in the chemotherapy group (Piecewise weighted average hazard ratio=0.71; 95% confidence interval [CI], 0.59-0.86, P=0.002). The most common treatment-related adverse events associated with tarlatamab treatments were cytokine release syndrome, dysgeusia and pyrexia. Yet, the incidence of adverse events of grade 3 or higher was lower with tarlatamab (54%) than the active control (80%).

In conclusion, tarlatamab immunotherapy prolongs overall survival than second-line chemotherapy in small-cell lung cancer patients whose disease had progressed despite platinum-based chemotherapy.

Source: www.nejm.org

Finerenone-Empagliflozin Leads to Greater Reduction in Urinary Albumin-to-Creatinine Ratio in Patients with Chronic Kidney Disease and Type 2 Diabetes

Date: August 7, 2025

Individuals suffering from both chronic kidney disease and type 2 diabetes are known as one of the high-risk groups for various cardiovascular diseases and kidney failure. The current clinical approach for such patient population involves the use of renin-angiotensin system blockers, sodium-glucose cotransporter-2 inhibitors (SGLT2i), finerenone, and glucagon-like peptide-1 receptor agonists. Yet, the effect regarding the concurrent use of finerenone and SGLT2i on reducing risk of chronic kidney disease and cardiovascular complications remains unknown.

In this double-blind, randomized, active-controlled CONFIDENCE trial, 800 patients having both type 2 diabetes with chronic kidney disease and albuminuria (with a urinary albumin-to-creatinine ratio between 100-5000) were recruited. Participants were randomly assigned in 1:1:1 ratio to receive oral (1) finerenone and empagliflozin-matching placebo (n=264), (2) empagliflozin and finerenone-matching placebo (n=267) or (3) finerenone-empagliflozin combination therapy (n=269) for 180 days. The primary endpoint was the relative change in log-transformed mean urinary albumin-to-creatinine ratio. Safety outcomes including the change in eGFR and its reversibility with stopping the therapy, or any known adverse events related to finerenone and empagliflozin use were assessed.

The reduction in the urinary albumin-to-creatinine ratio with combination therapy at day 180 was 29% greater than that with finerenone alone (least-squares mean ratio of the difference in the change from baseline=0.71, 95% confidence interval [CI], 0.61-0.82; P<0.001) and 32% greater than empagliflozin monotherapy (least-squares mean ratio of the difference in the change from baseline=0.68, 95% confidence interval [CI],0.59-0.79; P<0.001). None of the treatment groups had unexpected adverse events and the incidence of known adverse events leading to treatment discontinuation were uncommon.

To summarize, oral finerenone-empagliflozin therapy leads to a greater reduction in the urinary albumin-to-creatinine ratio than either treatment alone, which may further lower risk of cardiovascular diseases and kidney failure in patients with both chronic kidney disease and type 2 diabetes.

Source: www.nejm.org