Advances in Therapy最新文献

Introduction: Depemokimab, the first ultra-long-acting respiratory biologic, is under investigation for diseases with underlying type 2 (T2) inflammation. Subcutaneous depemokimab 100 mg was efficacious in patients with T2 asthma characterized by blood eosinophil count and in chronic rhinosinusitis with nasal polyps (CRSwNP) when administered twice-yearly in four Phase III randomized, double-blind, placebo-controlled studies (SWIFT-1/-2 and ANCHOR-1/-2, respectively). This pooled analysis examined the safety and tolerability of subcutaneous depemokimab 100 mg versus placebo in patients with T2 asthma and in CRSwNP.

Methods: Adverse event (AE) frequency, severity, time-to-onset, duration, and relative risk (RR) were evaluated for depemokimab 100 mg and placebo administered subcutaneously every 26 weeks for 52 weeks using pooled SWIFT-1/-2 and ANCHOR-1/-2 data. The impact of immunogenicity on safety was also evaluated.

Results: Overall, 1290 patients from the four studies were included in the safety analysis population (773 [60%] received depemokimab; 517 [40%] received placebo). On-treatment AEs were reported by 73% and 78% of patients in the depemokimab and placebo groups, respectively; the majority were mild or moderate in intensity and transient, with similar durations between treatment groups. Serious AEs (SAEs; 5% and 10%, with depemokimab and placebo, respectively), and discontinuations due to AEs (< 1% and 1%, respectively) were infrequent. No fatal AEs or treatment-related SAEs (per investigator assessment) were reported. RRs (vs. placebo) were similar for all common on-treatment AEs except asthma and back pain, which occurred less frequently in the depemokimab group compared with the placebo group. Antidrug antibodies and neutralizing antibodies occurred infrequently, and no association between antidrug antibody status and depemokimab efficacy was identified.

Conclusions: In these studies, twice-yearly depemokimab 100 mg was generally well tolerated by patients with T2 asthma or CRSwNP over the 52-week treatment period, supporting the safety of the first ultra-long-acting biologic for these diseases.

Clinical trial identifier(s): NCT04719832/NCT04718103/NCT05274750/NCT05281523.

Introduction: Spinal muscular atrophy (SMA) is a central nerve system disease characterized by a broad spectrum of clinical presentations, mainly manifested as muscle atrophy and weakness. The effectiveness and safety of nusinersen in Chinese adults with SMA have not been well reported. This analysis aimed to describe the effectiveness and safety of nusinersen among Chinese adults with 5q-SMA.

Methods: This analysis leveraged a longitudinal, multicenter disease registry including both prospective and retrospective data from adults with 5q-SMA in China. Nusinersen's effectiveness was assessed by the changes in the Hammersmith Functional Motor Scale Expanded (HFMSE), Revised Upper Limb Module (RULM), and 6-Minute Walk Test (6-MWT) from baseline and at 6, 10, and 14 months among participants receiving nusinersen as their first disease-modifying therapy (DMT). Nusinersen's safety was evaluated among prospective participants who used nusinersen as their first DMT and initiated nusinersen on or after the enrollment date.

Results: A total of 171 and 19 participants were included in the effectiveness and safety analysis, respectively. For HFMSE, the mean [standard deviation (SD)] change from baseline at 14 months after treatment initiation was 3.4 (5.34) among 17 sitters and 3.4 (4.03) among 25 walkers. For RULM, the mean (SD) change from baseline at 14 months after treatment initiation was 2.6 (3.07) among 11 non-sitters, 1.6 (4.06) among 20 sitters, and 1.3 (1.84) among 13 walkers. For 6-MWT, the mean (SD) change from baseline at 14 months after treatment initiation was 15.0 (35.80) m among 13 walkers. No death was reported in the registry. Three participants reported five mild adverse events, none of which were considered related to nusinersen by the investigators.

Conclusion: Despite the limited sample size, the analysis appears to show the benefit of nusinersen among Chinese adults of a wide range of ages and disease severity with 5q-SMA. The registry was registered on Clinicaltrials.gov (NCT05618379).

Introduction: Detecting paroxysmal atrial fibrillation (pAF) from sinus rhythm could enable earlier intervention and stroke prevention. We developed a deep-learning Holter electrocardiograph (ECG) algorithm and prospectively evaluated its patient-level performance against 7-day AF outcomes.

Methods: We curated 20,000 30-s sinus rhythm blocks (125 Hz) from Holter ECG data of patients with and without pAF, trained convolutional models with tenfold cross-validation, and assessed a separate validation set (n = 54; 27 pAF, 27 controls) to select the operating threshold. A multicenter prospective study then evaluated the algorithm using ten consecutive 30-s sinus rhythm blocks per patient with a 4/10 positive rule; patients with pAF underwent concurrent 7-day patch monitoring to anchor outcomes.

Results: Cross-validation during development yielded mean sensitivity 84.2% and specificity 66.2%; the best tuned model achieved 84.9% sensitivity and 69.9% specificity on the separate set. In the clinical trial, among 24 patients with AF documented within 7 days and 20 controls, the device showed sensitivity 91.7% (95% confidence interval (CI) 73.0-99.0) and specificity 65.0% (40.8-84.6). No device-related adverse events occurred.

Conclusion: An artificial intelligence (AI) analyzing short sinus rhythm Holter segments can identify patients who develop pAF within 7 days, supporting use as a triage tool for intensified rhythm monitoring.

Trial registration: UMIN-CTR UMIN000047182.

Introduction: Chronic kidney disease (CKD) symptom burden and associated treatments can impact patients' ability to work and financial well-being. Informal caregivers provide support and may also be affected. This multinational study aimed to characterise the impact of CKD on work productivity and the financial health of patients and caregivers.

Methods: National cohorts of patients with CKD, caregivers and matched general populations were recruited for Australia, Germany, Egypt, UK, Italy, Taiwan, and the US and surveyed via the Work Productivity and Activity Impairment (WPAI) questionnaire and the Consumer Financial Protection Bureau (CFPB) Financial Well-Being Scale. Financial toxicity was assessed using the COmprehensive Score for financial Toxicity-Functional Assessment of Chronic Illness Therapy (FACIT-COST).

Results: A total of 1303 patients and 674 caregivers were recruited. Compared with matched general populations, patients showed marked impairment in work and daily activities, particularly in presenteeism (difference: min, 7.4%; max, 43.6%) and activity impairment (difference: min, 25.9%; max, 46.4%). Work productivity and activity impairment were greatest among dialysis patients, a trend also observed among caregivers for patients on dialysis. CFPB Financial Well-Being scores indicated poorer financial health in patients versus general populations; variable outcomes were reported by caregivers. Financial toxicity, assessed by FACIT-COST, showed inter-country variation, and was most pronounced in younger, working-age patients.

Conclusion: The indirect burden of CKD extends beyond clinical costs to include significant financial and work productivity impacts on patients and caregivers, with greater challenges for patients on dialysis. Strategies to prevent CKD progression appear warranted to alleviate burden on financial health and work productivity for patients and caregivers.

Introduction: Obesity management medications influence eating behavior and promote substantial weight reduction in individuals with obesity or overweight. Existing patient-reported outcome measures do not adequately measure appetite and eating behavior concepts relevant to individuals with these conditions. This study presents psychometric properties of the Eating Behavior and Appetite Questionnaire (EBAQ), a new patient-reported outcome measure to assess appetite and eating behaviors in adults with obesity or overweight.

Methods: Participants (n = 120) completed two web-based surveys (baseline, week 2). Survey 1 included the 21-item EBAQ, Control of Eating Questionnaire, Food Cravings Questionnaire-Trait-reduced, Impact of Weight on Quality of Life-Lite Clinical Trials Version, and Patient Global Impression of Severity (PGIS) items for appetite, eating control, cravings, and overall eating behavior. Survey 2 included the EBAQ and PGIS items. Factor structure, reliability, and validity of the EBAQ were assessed.

Results: Exploratory factor analysis of the EBAQ supported a 2-factor structure. Items loaded moderately to strongly (≥ 0.48) on factors corresponding to appetite control or eating behavior (inter-factor correlation 0.57). Four items with factor loadings ≤ 0.43 were dropped. Internal consistency for the 17-item EBAQ was good/excellent for the domain scores (0.84-0.91) and excellent for the total score (0.92). Test-retest reliability was good (intraclass correlation coefficients ≥ 0.84). Convergent validity was demonstrated via large correlations with the Control of Eating Questionnaire craving subscales, Food Cravings Questionnaire-Trait-reduced total score, and PGIS items, and smaller correlations with less similar PRO measures. EBAQ domain and total scores demonstrated known-groups validity, with higher EBAQ scores in participants who reported a well-controlled appetite, feeling in control of their eating, fewer food cravings, and better eating habits (i.e., higher PGIS scores).

Conclusion: Results support the 2-factor structure, reliability, and validity of the final 17-item EBAQ. The EBAQ can be used in observational studies, clinical trials, and clinical practice to comprehensively assess appetite and eating behaviors in individuals with obesity or overweight.

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.