Advances in Therapy最新文献

Introduction: Over the past 2 decades, treatment for type 2 diabetes (T2D) has evolved with the introduction of medications that offer greater simplicity. The Simplicity of Diabetes Treatment Questionnaire (Sim-Q™) was developed to assess the simplicity or complexity of treatment for T2D. This study assessed the psychometric properties of the Sim-Q.

Methods: Eight clinical sites in the USA recruited participants treated for T2D with a variety of medications, including oral medications, insulin, glucagon-like peptide 1 (GLP-1) receptor agonists, and a dual glucose-dependent insulinotropic polypeptide and GLP-1 receptor agonist. Psychometric analysis of the Sim-Q focused on item performance, item selection, exploratory factor analysis (EFA), reliability (internal consistency and test-retest), and validity (construct and known-groups).

Results: The study included 250 participants (mean age 59.7 years; 54.4% female). On the basis of item performance and EFA, eight items were retained for the Simplicity of Diabetes Management Subscale assessing simplicity of treatment attributes. Two global items assessing simplicity of medication for diabetes and simplicity of overall diabetes management were scored separately. The Simplicity of Diabetes Management Subscale had good internal consistency reliability (Cronbach's alpha 0.90). The Simplicity of Diabetes Management Subscale and two global items had acceptable test-retest reliability (intraclass correlation coefficients 0.80, 0.72, and 0.73). Convergent validity was supported by significant correlations (P < 0.0001) with related measures. The Sim-Q distinguished between groups of participants who differed in their satisfaction with the ease and convenience of their treatment. For example, the two global items differentiated between groups receiving different treatments (tirzepatide and injectable semaglutide).

Conclusion: The Sim-Q demonstrated good reliability and validity in this psychometric study. This measure may be useful for assessing individuals' perceptions of treatment simplicity in clinical trials and clinical practice.

Introduction: This study aimed to identify potential concepts of interest (COIs) and clinical outcome assessments (COAs) for late-onset and infantile-onset Pompe disease (LOPD and IOPD) and to assess whether the current COAs are reliable and valid to capture patients' experiences.

Methods: Two literature reviews were conducted to identify, describe, and document key signs, symptoms, and impacts relevant to patients and to identify COAs used in Pompe disease. The COAs identified were mapped against the potential COIs to determine which instruments provided the best concept coverage from a patient perspective. Shortlisted COAs were further examined to assess their content validity and psychometric properties.

Results: Sixteen articles for LOPD and 9 for IOPD were identified for concept extraction. Patients with Pompe disease experience a range of signs, symptoms, and impacts. Most COAs currently used in Pompe disease are generic; only 3 LOPD COAs and 1 IOPD COA were disease-specific. Following mapping, 14 instruments for LOPD and 4 for IOPD were identified as providing the greatest coverage, with notable evidence gaps supporting content validity and/or psychometric properties of all shortlisted COAs.

Conclusion: Several COIs were identified from the literature that may be of importance to patients with Pompe disease. Individual COAs frequently used in assessing these concepts were found to have gaps with regards to content validity and psychometric properties. Additional research with patients with Pompe disease could be considered to address issues of content validity. Furthermore, the use of several COAs could be considered in future studies to capture what matters most to patients with Pompe disease.

Introduction: Pulmonary arterial hypertension (PAH) is a progressive, often fatal disease characterized by an elevation in pulmonary arterial pressure and pulmonary vascular resistance (PVR). Oral treprostinil is indicated for the treatment of PAH and has been shown to delay disease progression and to improve exercise capacity.

Methods: The purpose of this report is to examine and summarize the data on the use of oral treprostinil in patients already on dual therapy with an endothelin receptor antagonist (ERA) and phosphodiesterase type-5 inhibitor (PDE-5i), using data from the FREEDOM-C study, FREEDOM-C2 study, and a retrospective chart review.

Results: In this analysis, background monotherapy versus dual therapy did not have an impact on clinical parameters (6-min walk distance). Additionally, the number of background therapies did not have an impact on the dose of oral treprostinil achieved at week 16 or measures typically used to assess clinical efficacy in patients with PAH (change in 6MWD at week 16 and NT-proBNP).

Conclusion: Oral treprostinil is a safe and efficacious treatment option and has been shown to further improve clinical parameters and risk status in patients with PAH on background dual therapy.

Trial registry: ClinicalTrials.gov identifier, NCT00325442 and NCT00887978.

The prevalence of obesity continues to rise, with notable increase in stage III obesity in North America. The accumulation of excess adipose tissue can impair health with cardiovascular disease being the leading cause for increased mortality in people with obesity. The chronicity of the condition makes sustainable weight loss and improved health difficult for many with lifestyle changes alone, often necessitating the need for pharmacotherapy and bariatric surgery. Bariatric surgery remains the most efficacious treatment for obesity, despite improved pharmacotherapies. However, its low acceptability and accessibility render it an underutilized treatment. Meanwhile, the use of obesity pharmacotherapy, especially glucagon-like peptide 1 receptor agonists (GLP1RA) has become widespread with significant weight loss and improved health outcomes in randomised control trials. The real-world effectiveness of GLP1RA is hindered by issues including cost and tolerability. This narrative review discusses strategies to improve the effectiveness of pharmacotherapy and bariatric surgery and posits that bariatric surgery will continue to play an important role in obesity treatment in the GLP1RA era.

Introduction: Treatment for patients with chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) has shifted from chemoimmunotherapy (CIT) to targeted therapies, administered as continuous treatment until progression or in fixed-duration regimens. Fixed-duration regimens with targeted therapies (usually in combination regimens with venetoclax and a Bruton tyrosine kinase inhibitor [BTKi] and/or an anti-CD20 monoclonal antibody) are of increasing interest, and recent phase 3 trial results support this approach. Fixed-duration treatment offers a pre-defined treatment stopping point and may provide patients with a treatment-free interval, potentially reducing the burden of long-term therapy while minimizing cumulative toxicity and costs.

Methods: Here, we review the currently approved fixed-duration regimens and some investigational combinations in ongoing registrational clinical trials.

Results: The registrational fixed-duration studies CLL14 (venetoclax plus obinutuzumab), GLOW (ibrutinib plus venetoclax), CAPTIVATE (ibrutinib plus venetoclax), AMPLIFY (acalabrutinib plus venetoclax with or without obinutuzumab), and MURANO (venetoclax plus rituximab) along with the investigator-initiated CLL17 study, which may impact treatment guidelines, demonstrated extended treatment-free intervals. Generally, targeted fixed-duration regimens in patients with unmutated immunoglobulin heavy chain variable region or TP53 and/or del(17p) demonstrated greater efficacy than CIT, but outcomes were typically poorer than in patients without these high-risk features. Cardiovascular toxicity and death remain a significant concern with ibrutinib plus venetoclax, which was also associated with high rates of diarrhea and atrial fibrillation.

Conclusion: Successful fixed-duration regimens in CLL should achieve deep remission (i.e., undetectable minimal residual disease), sustain long-term progression-free survival, decrease the burden of treatment-related adverse events, and allow for re-treatment with minimal risk of drug resistance. Although fixed-duration treatment represents a positive step forward for most patients with CLL/SLL, the currently approved regimens often fall short in patients at high risk of progression. Continued research and development of next-generation drugs is essential to enhance efficacy and safety, ultimately improving outcomes in all patients with CLL/SLL.

Introduction: Gestational trophoblastic neoplasia (GTN) is a highly curable malignancy arising from placental trophoblasts, yet a small subset of patients develops multidrug resistance with limited therapeutic options. The discovery of high programmed death-ligand 1 (PD-L1) expression across trophoblastic tumors has provided a compelling biological rationale for immunotherapy, particularly immune checkpoint blockade targeting the PD-1/PD-L1 axis.

Objective: To summarize current evidence on immunotherapy in GTN, integrating biological foundations, clinical experiences, and ongoing clinical trials, and to discuss future perspectives toward individualized, fertility-preserving management.

Methods: A narrative review was conducted according to structured PRISMA-based principles. Literature was retrieved from PubMed, Scopus, and Web of Science from 2000 to 2025 using predefined descriptors related to GTN and immunotherapy. Eligible studies included clinical trials, case series, case reports, and translational research addressing immune checkpoint inhibitors in GTN.

Results: GTN exhibits high PD-L1 expression, mirroring the immune-privileged nature of the placenta. Checkpoint inhibitors alone, such as pembrolizumab, avelumab, or the combination of camrelizumab plus apatinib (that potently suppresses the kinase activity of vascular endothelial growth factor 2), have demonstrated complete and durable responses in approximately 70-80% of patients with multidrug-resistant GTN, with acceptable safety and preserved fertility.

Conclusions: Immunotherapy has expanded therapeutic GTN, transforming refractory disease as a result of its immune responsiveness. Checkpoint inhibition not only achieves high remission rates but also offers fertility preservation and long-term survivorship. The future challenge lies in optimizing combination strategies, refining biomarkers, and ensuring equitable global access to these emerging treatments.

Introduction: The relative efficacy of ciltacabtagene autoleucel (cilta-cel) and idecabtagene vicleucel (ide-cel) in relapsed/refractory multiple myeloma (RRMM) was assessed via unanchored matching-adjusted indirect comparison (MAIC) using data from the CARTITUDE-4 and CARTITUDE-1 (cilta-cel) and KarMMa-3 (ide-cel) trials. This updated MAIC includes longer follow-up and overall survival (OS).

Methods: An unanchored MAIC was performed utilizing individual patient-level data (IPD) from CARTITUDE-4 [1-3 prior lines of therapy (LOT); n = 208] and CARTITUDE-1 (3-4 prior LOT; n = 37). Patients fulfilling KarMMa-3 inclusion criteria (2-4 prior LOT, triple-class exposed) were selected, and outcomes were compared against published aggregate KarMMa-3 data. Cilta-cel IPD were weighted to match reported baseline characteristics of KarMMa-3 on key prognostic factors identified a priori. Comparative efficacy was estimated for progression-free survival (PFS), OS, overall response rate, very good partial response (VGPR) or better rate, and complete response (CR) or better rate.

Results: Eighty-five patients from CARTITUDE-4 and CARTITUDE-1 were included. After adjustment, patients in the cilta-cel group (effective sample size = 39) had a 58% reduction in PFS risk [hazard ratio (HR) 0.42 (95% CI 0.26-0.68); p = 0.0004] and a 42% reduction in OS risk [HR 0.58 (0.34-0.99); p = 0.0452] versus ide-cel. Patients in the cilta-cel group were significantly more likely to achieve an overall response [relative response ratio (RR) 1.22 (95% CI 1.08-1.38); p = 0.0126] and deeper levels of response [≥ VGPR: RR 1.37 (1.19-1.59); p = 0.0009; ≥ CR: RR 1.80 (1.49-2.18); p < 0.0001] versus ide-cel.

Conclusion: This updated MAIC with longer follow-up time demonstrated significant superiority of cilta-cel over ide-cel in PFS, OS, and response outcomes in patients with triple-class exposed RRMM treated with 2-4 prior LOT. The OS results reinforce the added value of cilta-cel in this population.

Trial registration: ClinicalTrials.gov ID: CARTITUDE-1: NCT03548207; CARTITUDE-4: NCT04181827; KarMMa-3: NCT03651128.

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: 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: 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.