Advances in Therapy最新文献

Introduction: To date, no study has compared the healthcare resource utilization (HCRU), costs, and discontinuation of the two calcitonin gene-related peptide antagonists, galcanezumab (monoclonal antibody subcutaneously injected monthly) and rimegepant (oral gepant taken every other day), for migraine prevention. This study aimed to assess all-cause and migraine-related HCRU, costs, and treatment discontinuation at 12 months following treatment initiation in commercial/Medicare beneficiaries with episodic migraine who received galcanezumab versus rimegepant as preventive migraine treatment.

Methods: This retrospective study used the Merative™ MarketScan^® Research Databases (June 2020-June 2023). Adults with episodic migraine were grouped into the galcanezumab (≥ 1 claim) or rimegepant cohort (≥ 1 claim with quantity ≥ 15 during the index period). Changes from baseline in all-cause and migraine-related HCRU and cost between the propensity score-matched cohorts were determined using Wilcoxon signed rank test and chi-square test. Treatment discontinuation was assessed using Kaplan-Meier analysis and Cox proportional hazards model.

Results: All-cause and migraine-related HCRU and costs increased over the 12-month follow-up in both cohorts. The galcanezumab cohort had a significantly lower increase in mean all-cause total medical + pharmacy costs (21% lower) and migraine-related total medical + pharmacy costs (76% lower) than the rimegepant cohort at the 12-month follow-up (p < 0.0001 for both assessments). Mean (standard deviation) number of days from initiation to discontinuation (> 60-day gap) was 244.6 (135.3) for galcanezumab cohort and 178.1 (141.1) for rimegepant cohort (p < 0.0001). Treatment discontinuation rate was 1.8 times less likely in the galcanezumab cohort than the rimegepant cohort (hazard ratio = 1.81, 95% confidence interval = 1.56-2.10). Similar trends were observed using a 30-day gap.

Conclusion: Among matched patients, both cohorts of patients with episodic migraine showed all-cause and migraine-related total cost increases over 12 months. However, the magnitude of the increases was significantly lower for the galcanezumab cohort than for the rimegepant cohort. Treatment discontinuation rate was significantly lower in the galcanezumab versus the rimegepant cohort.

Introduction: Previous studies, using clinical trial data, demonstrated that once-weekly (OW) semaglutide is dominant versus other glucagon-like peptide 1 receptor agonists (GLP-1 RAs) in China. This study aims to evaluate the long-term clinical and economic effects of switching to OW semaglutide from other GLP-1 RAs among patients with type 2 diabetes mellitus (T2DM) in China.

Methods: The Institute of Health Economics Diabetes Cohort Model (IHE-DCM) was used to project life expectancy, quality-adjusted life years (QALYs), and total direct medical cost over 40 years from a Chinese healthcare system perspective. Baseline characteristics, clinical effectiveness, and the treatment dose of OW semaglutide were derived from previously real-world studies. Patients were assumed to switch to semaglutide or continue previous GLP-1 RAs for 3 years and change to intensive therapy. Drug prices were based on the median bidding price in January 2024 in China. Costs of other GLP-1 RAs were calculated on the basis of their market share in China. All costs were accounted as 2023 Chinese yuan (CNY). A discount of 5% was applied. One-way sensitivity analyses and probabilistic sensitivity analyses were used to test the robustness of the base-case result.

Results: The results show that switching to OW semaglutide from other GLP-1 RAs among patients with T2DM in China can improve life expectancy by 0.02 years and afford an additional 0.12 QALYs per patient. Meanwhile, switching to OW semaglutide is associated with decreased total lifetime direct medical costs of 4204 CNY per patient, mainly resulting from savings in microvascular costs (2214 CNY) and macrovascular costs (1228 CNY). Sensitivity analyses show the robustness of modeling projection findings.

Conclusion: Based on real-world data from China, this modeling projection study demonstrates that switching to OW semaglutide from other GLP-1 RAs can have better clinical and economic effects for patients with T2DM in China, indicating it as a dominant treatment choice.

Introduction: The Quality of Life-Bronchiectasis (QOL-B) questionnaire and Patient Reported Outcome Measurement Information System Short Form v1.0-Fatigue 7a (PROMIS-F SF-7a) have the potential to measure respiratory and fatigue symptoms, respectively, in patients with Mycobacterium avium complex (MAC) lung disease but have not yet been evaluated for content validity in this population.

Methods: Semi-structured qualitative interviews were conducted in United States patients with a current MAC lung disease diagnosis. Concept elicitation (CE) interviews were conducted (n = 25 participants) to identify key respiratory and fatigue symptoms expressed as important and relevant to patients with MAC lung disease and to evaluate the appropriateness of the QOL-B and PROMIS-F SF-7a to measure these symptoms. Cognitive interviews (CIs) were subsequently conducted (n = 20 participants) to evaluate the relevance, comprehensibility, and appropriateness of the QOL-B respiratory domain (QOL-B-RD) and PROMIS-F SF-7a. All interviews were recorded, transcribed, and coded for qualitative content analysis.

Results: The most important or relevant respiratory symptom concepts to CE interview participants were "cough," "shortness of breath during activity," and "mucus/phlegm." The most important or relevant fatigue symptom concepts were "tiredness," "lack of energy," and "tire easily/low stamina." These symptoms are covered by existing items in the QOL-B-RD and PROMIS-F SF-7a. Cognitive interview participants' feedback confirmed the item content, response options, concept attributes, and recall period for each instrument were effective, relevant, and meaningful to most patients with MAC lung disease. Based on Wave 1 findings, the QOL-B instructions were revised for the Wave 2 interviews, where the text referencing "bronchiectasis" was replaced with "your lung condition." Participant feedback in Wave 2 confirmed the revised instruction wording was easily understood and appropriate.

Conclusions: The study results support the content validity of the QOL-B-RD and PROMIS-F SF-7a, which were shown to be relevant and appropriate to evaluate respiratory and fatigue symptoms, respectively, in patients with MAC lung disease.

Coronavirus disease 2019 (COVID-19) caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has had a profound global impact. The emergence of several variants during the pandemic has presented numerous challenges in preventing and managing this disease. The development of vaccines has played a pivotal role in controlling the pandemic, with a significant portion of the global population being vaccinated. This, along with the emergence of less virulent SARS-CoV-2 variants, has led to a reduction in the severity of COVID-19 outcomes for the overall population. Nevertheless, individuals with immunocompromising conditions continue to face challenges given their suboptimal response to vaccination and vulnerability to severe COVID-19. This expert review synthesizes recent published evidence regarding the economic and human impact of COVID-19 on such individuals. The literature suggests that rates of hospitalization, intensive care unit admission, and mechanical ventilation use were high during the pre-Omicron era, and remained high during Omicron and later, despite vaccination for this population. Moreover, studies indicated that these individuals experienced a negative impact on their mental health and health-related quality of life (HRQoL) compared to those without immunocompromising conditions, with elevated levels of anxiety, depression, and distress reported. Further, these individuals with immunocompromising conditions experienced substantial costs associated with COVID-19 and loss of income during the pandemic, though the evidence on the economic burden of COVID-19 in such individuals is limited. Generally, COVID-19 has increased healthcare resource use and costs, impaired mental health, and reduced HRQoL in those with varied immunocompromising conditions compared to both those without COVID-19 and the general population-underscoring the importance of continued real-world studies. Ongoing research is crucial to assess the ongoing burden of COVID-19 in vaccinated individuals with immunocompromising conditions who are still at risk of severe COVID-19 outcomes to ensure their needs are not disproportionately worse than the general population.

Introduction: Individuals living with sickle cell disease (SCD) commonly report impaired health-related quality of life (HRQoL). However, impacts of SCD on HRQoL and the unmet needs of SCD treatment/management are under-researched. This study characterized the impact of SCD on HRQoL and identified the unmet needs of individuals with SCD.

Methods: Adults with SCD (aged ≥ 18 years) and caregivers of adolescents (aged 12‒17) with SCD in the United States (US) and United Kingdom (UK) participated in one-on-one virtual semi-structured interviews and focus group discussions (hereafter referred to as 'interviews'). Interviews were transcribed and thematically analyzed.

Results: Nineteen individuals participated in the study (across five interviews and three focus group discussions), including 18 adults with SCD (United States, n = 11; United Kingdom, n = 7) and one caregiver of an adolescent with SCD (United States). Most participants were female (n = 15). Participants reported negative impacts of SCD on their HRQoL, including the burden of structuring their lives around SCD, due to unpredictable symptoms. They reported negative impacts to psychological health (e.g., depression/low mood and anxiety) and physical health (e.g., chronic pain and fatigue) that affected their social and family life, work, and education, leading to feelings of isolation. Participants expressed concerns about the future, feelings of resentment, and the need for high resilience when facing the barriers/impacts associated with SCD. Many participants reported negative interactions with healthcare professionals, leading to trauma, anxiety, and routine care avoidance. Most participants reported perceived prejudice during routine SCD treatment/management, including being treated as drug-seekers.

Conclusion: Individuals with SCD experience negative HRQoL impacts, including impacts to daily activities, social and family life, work and education, psychological health, and prejudice/stigma. Our findings highlight significant unmet needs of individuals living with SCD, including alternative treatment options to reduce vaso-occlusive crisis (VOC) frequency and treat fatigue.

Introduction: This study compared the relative efficacy of first-line lenvatinib, a standard-of-care treatment for unresectable hepatocellular carcinoma (uHCC), vs licensed/license in-progress comparators. Using inverse probability of treatment weighting (IPTW) and network meta-analysis (NMA), updated evidence for lenvatinib monotherapy from LEAP-002, in addition to evidence from REFLECT, was included in the analyses.

Methods: Randomized controlled trials (RCTs) were identified via systematic review. REFLECT and LEAP-002 investigated lenvatinib in uHCC, with patient-level data available for each; however, only REFLECT included a comparator arm of interest (sorafenib). The lenvatinib arm from LEAP-002 was adjusted to match aggregate data for confounding factors from REFLECT using IPTW. Weighted Cox regressions, including matching variables as covariates, were used to derive hazard ratios (HRs) for overall survival (OS) and progression-free survival (PFS). These HR estimates were included in Bayesian NMAs to compare lenvatinib with comparators; survival was significantly improved if the 95% credible interval for the HR did not include 1.0. Scenario analyses explored alternative choices for IPTW estimators.

Results: Eight RCTs (including REFLECT) and the single-arm adjusted lenvatinib data from LEAP-002 were included in the NMA base case. Lenvatinib demonstrated significant improvement in OS compared with sorafenib 400 mg twice daily (BID) and significant improvement in PFS compared with sorafenib 400 mg BID, tremelimumab 300 mg plus durvalumab 1500 mg every 4 weeks (Q4W), and durvalumab 1500 mg Q4W.

Conclusions: These results suggest that patients with uHCC treated with lenvatinib have similar or significantly improved OS and PFS compared with licensed/license in-progress therapies.

Introduction: Patients with uncontrolled, moderate-to-severe asthma have a higher risk for exacerbations, negatively impacting lung function and quality of life. Dupilumab, a fully human monoclonal antibody, blocks interleukins 4 and 13, key and central drivers of type 2 inflammation. Dupilumab has been effective in the treatment of certain types of moderate-to-severe asthma across several clinical trials. We describe the characteristics of patients enrolled in RAPID, a global prospective registry, who initiated dupilumab (primary indication: asthma) in a real-world clinical setting.

Methods: A total of 205 patients (aged ≥ 12 years) were enrolled between March 2020 and October 2021 and are included in this analysis. Data are shown as mean (SD) unless stated otherwise.

Results: Patients were aged 50.1 (17.4) years and were mostly female (65.4%) and white (74.1%). At enrollment, 24.4% reported being current/former smokers and 86.8% had moderate-to-severe asthma (Global Initiative for Asthma steps 3-5). A mean (SD) of 4.4 (6.4) severe asthma exacerbations were reported in the year before enrolling in the registry in 78 of 152 patients with available data. Patients had reduced lung function [pre-bronchodilator forced expiratory volume in 1 s (FEV₁): 2.3 (1.1) L; pre-bronchodilator percent predicted FEV₁: 70.3 (20.3) %] and poor asthma control [6-item Asthma Control Questionnaire: 2.4 (1.2); Asthma Quality of Life Questionnaire: 4.1 (1.3)]. The median (Q1-Q3) blood eosinophil count was 305 (200-695) cells/µL and the mean (SD) fractional exhaled nitric oxide levels were 42 (35) ppb (range: 4-186 ppb).

Conclusion: Our findings suggest that most patients who enrolled in RAPID and initiated dupilumab in real-world clinical settings had a high disease burden, despite receiving current standard-of-care treatment at enrollment.

Acute coronary syndrome (ACS) is a leading cause of death worldwide. Prompt and accurate diagnosis of acute myocardial infarction (AMI) or ACS is crucial for improved management and prognosis of patients. The rapid growth of machine learning (ML) research has significantly enhanced our understanding of ACS. Most studies have focused on applying ML to detect ACS, predict prognosis, manage treatment, identify risk factors, and discover potential biomarkers, particularly using data from electrocardiograms (ECGs), electronic medical records (EMRs), imaging, and omics as the main data modality. Additionally, integrating ML with smart devices such as wearables, smartphones, and sensor technology enables real-time dynamic assessments, enhancing clinical care for patients with ACS. This review provided an overview of the workflow and key concepts of ML as they relate to ACS. It then provides an overview of current ML algorithms used for ACS diagnosis, prognosis, identification of potential risk biomarkers, and management. Furthermore, we discuss the current challenges faced by ML algorithms in this field and how they might be addressed in the future, especially in the context of medicine.

Introduction: This analysis evaluated literature on patients with activated phosphoinositide 3-kinase delta syndrome (APDS) to better understand the genetic etiologies and occurrence of mortality in this population.

Methods: A systematic review was performed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses approach, including all articles published in English prior to March 13, 2023, in PubMed and Embase. Patients included in the study had reported either (1) APDS diagnosis or (2) ≥ 1 clinical sign consistent with APDS and a first-degree relative with genetically confirmed APDS. Reported age at last observation was also a required outcome. Publications not meeting these criteria were excluded. Data were summarized using descriptive statistics.

Results: The search identified 108 publications describing 351 unique patients with 39 distinct disease-causing variants. Among these, 41 (12%) deaths were reported, with a mean age at last follow-up of 19.6 (range, 1-64) years. A cause of death was reported for 80% (33/41) of deaths; lymphoma (24%, 10/41) and infections (22%, 9/41) were the most common causes. Types of infections causing death were severe uncontrollable infections (n = 3), sepsis (n = 2), viral infection (varicella zoster pneumonitis [n = 1], cytomegalovirus and adenovirus [n = 1], and Epstein-Barr virus [n = 1]), and infection (n = 1). Mean age at death for lymphoma was 24.9 (range, 1-41) years, and all nine patients who died from infections died before the age of 15 years. The mean age at first APDS symptom was 2.0 (range, < 1-22) years, and mean age at APDS diagnosis was 13.4 (range, 0-56) years; the mean time between symptoms and diagnosis was 10.6 (range, 0-44) years. Limitations of the study were primarily related to the data source.

Conclusion: Patients with APDS suffer early mortality, largely from lymphoma and infection, with large time gaps between symptoms and diagnosis. These findings highlight the need for improved diagnostics, earlier genetic testing for APDS, increased awareness of familial testing, and targeted therapies.

Introduction: To investigate outcomes in adults with type 2 diabetes who switched to once-weekly (OW) semaglutide from another glucagon-like peptide-1 receptor agonist (GLP-1RA) in clinical practice.

Methods: This post hoc analysis used data from the SemaglUtide Real-world Evidence (SURE) program, which included nine observational studies investigating the initiation of OW semaglutide in people with type 2 diabetes in routine clinical practice. Using a random coefficient-adjusted mixed model for repeated measurements, changes in glycosylated hemoglobin (HbA_1c), body weight, and body mass index were analyzed for GLP-1RA-experienced patients who had at least one documented HbA_1c value within the 12 weeks before switching to OW semaglutide. In addition, descriptive statistics were used for HbA_1c, body weight target achievement, and safety data.

Results: Of the 3,505 patients included in the nine SURE studies, 651 switched to OW semaglutide from another GLP-1RA. GLP-1RA-experienced patients who switched to OW semaglutide demonstrated a 0.67%-point [95% confidence interval (CI) - 0.74; - 0.60, p < 0.0001] reduction in HbA_1c, and a 3.69-kg [95% CI - 3.98; - 3.41, p < 0.0001] reduction in body weight over 30 weeks. A body weight reduction of ≥ 5% was achieved by 27.6% of patients, and 33.3% of patients with baseline HbA_1c ≥ 7% achieved HbA_1c < 7% at end of study. No new safety concerns were identified.

Conclusions: Data from this post hoc analysis suggest that, for those not adequately responding to treatment with other GLP-1RAs, switching to OW semaglutide could provide additional glycemic and weight benefits with the convenience of an OW dosing regimen.