Advances in Therapy最新文献

Introduction: Early identification allows timely guideline-directed therapy to prevent progression to symptomatic heart failure (HF). N-terminal pro-B-type natriuretic peptide (NT-proBNP) is an established biomarker for screening asymptomatic patients at risk of HF, yet real-world outpatient data in the Middle East are scarce. This study aimed to identify adults with NT-proBNP ≥ 125 pg/mL who may need cardiac evaluation and recognize clinical predictors of elevated NT-proBNP.

Methods: This retrospective chart review included adults with type 1 or type 2 diabetes mellitus (DM) (≥ 18 years) tested for NT-proBNP at a tertiary care center in Riyadh, Saudi Arabia (January 2024-June 2025). Individuals with prior HF or advanced chronic kidney disease were excluded. NT-proBNP ≥ 125 pg/mL defined patients at increased risk of pre-HF. Multivariable logistic regression analysis assessed variables independently related to NT-proBNP above the prespecified cutoff.

Results: Among 152 patients (median age 54 years; 41.5% female), those with type 2 DM were older than those with type 1 DM (median age 58 vs. 38 years), had higher body mass index (median 30.1 vs. 26.8 kg/m²), and had a greater burden of cardiometabolic comorbidities (hypertension 61.2% vs. 26.1%; dyslipidemia 71.3% vs. 30.4%). In the type 2 DM subgroup (n = 129), 52.7% had NT-proBNP ≥ 125 pg/mL (median DM duration 17 years). NT-proBNP levels were higher in older patients (adjusted OR 1.13/year; p = 0.029) as well as in patients with higher systolic blood pressure (adjusted OR 1.09/mmHg; p = 0.007), as assessed using multivariable analysis.

Conclusion: More than half of asymptomatic adults with type 2 DM had NT-proBNP levels exceeding the American Diabetes Association (ADA)-recommended threshold of ≥ 125 pg/mL, suggesting a substantial burden of pre-‍HF in an outpatient setting. NT-proBNP-based screening could facilitate early identification of high-risk patients, facilitating timely cardiac evaluation with initiation of guideline-directed therapies to prevent, delay, or avert progression to symptomatic HF.

Introduction: Clinical remission (CR) is an emerging treatment goal in asthma. However, evidence showing whether CR is achievable with inhaled therapy is lacking. This post hoc analysis of CAPTAIN evaluated attainability of a composite CR endpoint with inhaled fluticasone furoate/umeclidinium/vilanterol (FF/UMEC/VI) or FF/VI.

Methods: CAPTAIN (GSK 205715) was a Phase IIIA, randomized, controlled, 24-52-week trial comparing once-daily single-inhaler FF/UMEC/VI versus FF/VI in adults with uncontrolled moderate-to-severe asthma despite ICS/LABA. CR was defined as a composite endpoint comprising no systemic corticosteroids, no severe exacerbations, ACQ-5 total score < 1.50, and either change from baseline in FEV₁ ≥ 0 ml (lung function stabilization) or ≥ 100 ml (lung function optimization), assessed for patients meeting the CR endpoint at Week 24 (W24) and achieving CR at W52 with FF/UMEC/VI (100/62.5/25, 200/62.5/25 μg) versus FF/VI (100/25, 200/25 μg). Additional analyses assessed the CR endpoint at W24/W52 using ACQ-5 ≤ 0.75 and ≤ 1.00 thresholds. Adjusted odds/risk ratios for CR were calculated for W24.

Results: More patients met the CR endpoint (lung function stabilization/optimization) with FF/UMEC/VI versus FF/VI at W24 (stabilization: 42-47% vs 31-36%; optimization: 31-36% vs 19-26%) and W52 (stabilization: 43-47% vs 33-34%; optimization: 30-38% vs 21-24%). Using more stringent ACQ-5 thresholds, fewer patients met the CR endpoint with ACQ ≤ 0.75 versus < 1.50 across treatment arms and timepoints. The odds and probability of meeting the CR endpoint versus not meeting the CR endpoint at W24 were greater with FF/UMEC/VI versus FF/VI, regardless of FF dose.

Conclusion: The results of this post hoc analysis demonstrate that CR is achievable with inhaled therapy in moderate-to-severe asthma and is more likely with FF/UMEC/VI than FF/VI. CR should be considered an attainable treatment goal for patients with asthma, irrespective of disease severity or treatment history.

Trial registration: ClinialTrials.gov identifier, NCT02924688.

Introduction: Chronic kidney disease (CKD) can negatively impact the quality of life (QoL) of patients and caregivers. Determinants of QoL may vary between countries and healthcare systems. Given the global prevalence of CKD, this multinational study aimed to quantify the impact of CKD on QoL for patients and caregivers worldwide.

Methods: Patients with CKD, caregivers and matched general population participants were recruited in Australia, Germany, Egypt, Italy, Mexico, Taiwan, the UK and the US. QoL was assessed by patient and caregiver response to EQ-5D-5L, and also to the CarerQol-7D instrument for caregivers. Subgroups were stratified by dialysis-dependence status.

Results: A total of 1382 patients and 813 caregivers were recruited. Across the surveyed country cohorts, patients reported significantly decreased EQ-5D-5L index scores versus matched general population cohorts (0.57-0.89 vs. 0.93-0.96, respectively; all p < 0.005), with greater impairment in dialysis-dependent patients versus non-dialysis-dependent patients (0.51-0.79 vs. 0.65-0.93, respectively). Patients typically reported significantly greater impairments across all EQ-5D-5L domains versus the general population. Caregivers reported lower mean EQ-5D-5L index scores versus matched general population cohorts (0.73-0.93 vs. 0.93-0.97, respectively). Caregivers reported mean CarerQol-7D index scores between 63.0 and 79.6, with numerically lower scores for caregivers of dialysis-dependent patients.

Conclusion: This is the first study that characterises the QoL burden of CKD in patients and caregivers on a multinational scale. Patients and caregivers experience a considerable QoL burden, particularly when dialysis-dependent. Strategies to alleviate burden, including prevention of CKD progression, financial and social supports, are required but may vary according to local context.

Introduction: Clinical remission (CR) is an ambitious and achievable treatment goal for many patients with severe asthma. This study evaluated real-life care of patients in the U.S. using CR criteria defined by the American Thoracic Society; American College of Allergy, Asthma, and Immunology; and American Academy of Allergy, Asthma & Immunology.

Methods: This retrospective cohort study (GSK ID: 219744) utilized data from the Mayo Clinic's electronic health record database (January 1, 2014-March 31, 2023). Eligible adults had severe asthma, ≥ 1 respiratory biologic initiated, and ≥ 12 months of clinical activity post-index date. The primary objective quantified the proportion of patients with documented CR component criteria 12-months post-biologic initiation. Criteria included asthma exacerbations, systemic corticosteroid use for asthma, missed work/school due to asthma, ≥ 2 pulmonary function tests, controller medication use for asthma, ≥ 2 asthma control tests, and rescue medication use for asthma.

Results: Of 4623 patients receiving respiratory biologics, 707 were eligible. Documentation was available for ≥ 1 component in 94.2% of patients; none had all criteria documented. Overall, 90.2%, 83.2%, 55.4%, and 33.0% of patients had documented controller medication use, rescue medication use, systemic corticosteroid use, and asthma exacerbations, respectively. For patients with documentation, 91.2% achieved ≥ 1 criterion. However, the proportion achieving remission decreased with the number of components; 0.6% of patients achieved ≥ 5 criteria. Of 141 (19.9%) patients receiving mepolizumab, documentation was available for ≥ 1 component in all patients; none had all criteria documented. The proportion of patients with documentation, and who achieved ≥ 1 to ≥ 4 criteria, was higher versus the overall population.

Conclusion: This study demonstrated infrequent documentation of the CR components in routine practice, thereby limiting the comprehensive evaluation of CR. Standardized assessment protocols encompassing all domains are needed to enable accurate assessment of CR, and for treatment targets to provide clear goals for clinicians and patients.

Introduction: The treatment landscape for focal seizures in China is distinct from those in other regions, with oxcarbazepine and sodium valproate being more commonly used than newer antiseizure medications (ASMs). Cenobamate, a novel ASM, has demonstrated significant efficacy in reducing seizure frequency. However, its efficacy and safety have not been assessed within the Chinese population.

Methods: The current study analyzed the 24-week double-blind period data of Chinese participants from a randomized, double-blind, placebo-controlled clinical trial (NCT04557085). Efficacy was assessed by determining seizure frequency reduction and responder rates across the cenobamate dose groups (100, 200, and 400 mg) and concomitant ASM groups. Safety was assessed by treatment-emergent adverse events (TEAEs) and treatment-related adverse events (TRAEs) during the double-blind treatment period.

Results: This post hoc analysis included 227 participants with a median age of 32 (interquartile range 24-40) years with focal seizures across 24 sites in China. Cenobamate demonstrated a greater median percentage reduction in seizure frequency (100 mg, 39.5%, 200 mg, 88.0%, 400 mg, 100.0%) compared to placebo (24.6%). The responder rate of ≥ 50% was higher in the cenobamate groups (100 mg, 35.4%, 200 mg, 76.0%, 400 mg, 89.4%) compared to the placebo group (22.0%). A greater seizure reduction and responder rates were observed when cenobamate was administered alongside sodium channel blockers (SCBs) and non-SCBs, demonstrating better efficacy compared to placebo. On the basis of the number of baseline ASMs, cenobamate demonstrated seizure reduction and higher responder rates across all ASM groups as compared with placebo. Cenobamate demonstrated an acceptable safety profile across all dosage groups, with most AEs being mild to moderate. Common TEAEs reported included dizziness and somnolence.

Conclusion: Cenobamate demonstrated a very favorable efficacy and safety profile in Chinese participants with focal seizures. The combination of cenobamate with both SCB and non-SCB treatments was effective in reducing seizure frequency and improved responder rates compared to placebo.

Introduction: PTEN hamartoma tumor syndrome (PHTS) is a rare genetic disorder caused by germline pathogenic variants in the PTEN tumor suppressor gene. Everolimus, an oral mTORC1 inhibitor, is approved for the treatment of tuberous sclerosis complex-related tumors; however, evidence for its efficacy in PHTS remains limited. A recent randomized controlled trial (RCT) reported safety and efficacy findings, but the composite primary efficacy endpoint did not reach statistical significance.

Methods: We conducted a sensitivity analysis of this RCT to further evaluate the efficacy of everolimus in PHTS. Five statistical approaches were applied: analysis of covariance and four linear mixed-effects models. Outcomes included the composite neurocognitive score as a primary endpoint and multiple secondary neurocognitive and behavioral measures.

Results: Across all analysis approaches, everolimus did not significantly improve the composite neurocognitive score compared with placebo. However, several secondary outcomes showed consistent benefits. Fine motor function assessed by the Purdue Pegboard Test (left hand) demonstrated sustained improvement over placebo across models. Social functioning, assessed by the total score (higher values indicating better functioning) of the reverse-coded Social Responsiveness Scale, second edition, improved over time, with significant differences observed at 6 months in the everolimus group. Several additional secondary endpoints showed consistent trends favoring everolimus.

Conclusion: Although the composite primary endpoint did not demonstrate significant improvement, sensitivity analyses identified potential benefits of everolimus in motor and social domains in individuals with PHTS. These results are consistent with the original trial findings and provide further support for investigating everolimus as a therapeutic option in this population.

In this literature review, branded and generic preserved latanoprost are compared with respect to comparative efficacy, tolerability, and physicochemical properties. Worldwide, latanoprost, a prostaglandin analogue, has evolved into the first-line medical treatment for patients with open-angle glaucoma or ocular hypertension. Following the launch of multiple latanoprost generic preparations, clinicians and patients face a dilemma between prescribing the original branded product or its more affordable generic counterparts. While, in theory, branded and generic latanoprost formulations share the same active and inactive ingredients, available studies comparing their efficacy have reported conflicting results. Further, published evidence has demonstrated several subtle and sometimes manifest differences in terms of active ingredient content, benzalkonium chloride (BAK) concentration, pH level, osmolality, particulate content, and drop size. Moreover, degradation of the active ingredient under adverse temperature conditions is reportedly more pronounced with generic latanoprost. Recorded differences may negatively affect long-term efficacy, tolerability, ocular surface health, and adherence. However, to what extent these differences play a role in glaucoma care over the long term remains to be determined. Until such information becomes available, latanoprost therapy should be individualized, and careful patient monitoring is recommended. We conclude that stricter regulatory oversight of antiglaucoma eyedrops should be sought to ensure the safety and consistency of action of all available generic formulations.