Advances in Therapy最新文献

Despite well-established vaccination programs, seasonal influenza is still causing substantial clinical, economic and societal burdens. As part of strategies to continually improve influenza vaccine clinical performance, several new approaches are being examined, including high-dose vaccines, adjuvanted vaccines, egg-free vaccines, nasal spray vaccines and mRNA vaccines. Given this range of influenza vaccines, coupled with various vaccine hesitancy concerns, healthcare professionals' understanding and confidence in the clinical performance of influenza vaccines remain key. In this podcast, we discuss the challenges for healthcare professionals in understanding the clinical performance of influenza vaccines and the importance of education in this area, particularly to address perceptions of influenza vaccine failure. We also explore several elements that should be considered in the assessment of influenza vaccine clinical performance: (1) assessing relevant clinical outcomes, such as hospitalization data, (2) utilizing robust methodology in influenza vaccine trials to ensure high quality evidence and (3) approaches used when considering the full body of evidence.

Introduction: Although clinical, functional, and biomarker data predict asthma exacerbations, newer approaches providing high accuracy of prognosis are needed for real-world decision-making in asthma. Machine learning (ML) leverages mathematical and statistical methods to detect patterns for future disease events across large datasets from electronic health records (EHR). This study conducted training and fine-tuning of ML algorithms for the real-world prediction of asthma exacerbations in patients with physician-diagnosed asthma.

Methods: Adults with ≥ 2 ICD9/10 asthma codes within 1 year and at least 30 days apart were identified from the Optum Panther EHR database between 2016 and 2023. An emergency department (ED), urgent care, or inpatient visit for asthma, while on systemic administration of corticosteroids, was considered an exacerbation. To predict factors associated with exacerbations in a 6-month study period, clinical information from patients was retrieved in the preceding 6-month baseline period. Clinical information included demographics, lab results, diagnoses, medications, immunizations, and allergies. Three models built using Extreme Gradient Boosting (XGBoost), Long Short-Term Memory (LSTM), and Transformers algorithms were trained and tested on independent datasets. Predictions were explained using the SHAP (SHapley Additive exPlanations) library.

Results: Of 1,331,934 patients with asthma, 16,279 (1.2%) experienced ≥ 1 exacerbation. XGBoost was the best predictive algorithm (area under the curve [AUC] = 0.964). Factors associated with exacerbations included a prior history of exacerbation, prednisone usage, high-dose albuterol usage, and elevated troponin I. Reduced probability of exacerbations was associated with receiving inhaled albuterol, vitamins, aspirin, statins, furosemide, and influenza vaccination.

Conclusion: This ML-based study on asthma in the real world confirmed previously known features associated with increased exacerbation risk for asthma, while uncovering not entirely understood features associated with reduced risk of asthma exacerbations. These findings are hypothesis-generating and should contribute to ongoing discussion of the strengths and limitations of ML and other supervised learning models in patient risk stratification.

Atopic dermatitis (AD) is a chronic, relapsing inflammatory skin condition that can have a negative impact on a patient's quality of life. Long-term effectiveness is required to manage the symptoms of AD (skin inflammation, eczematous lesions, and itching). Because some of the systemic immunosuppressants used to treat AD have been associated with serious adverse events (AEs), other safer, more effective options, including dupilumab, have been proven effective long-term for treatment of adult and adolescent patients with moderate-to-severe AD. The long-term safety and effectiveness of a drug are usually confirmed in real-world studies by evaluating its performance over time. Measures such as drug survival, drug retention, drug persistence, or retention rates reflect whether treatment may be considered as satisfactory by both patients and physicians, meeting key clinical needs. This review aimed to describe the survival, retention, or persistence of dupilumab therapy in adults and adolescents with moderate-to-severe AD by conducting a PubMed search in March 2023 and screening for relevant publications. Globally, real-world studies with dupilumab have regularly reported high drug survival rates after 1, 2, and 3 years of observation, being consistently at 80-90%, with low rates of treatment discontinuation due to lack of efficacy or AEs. These findings are notably higher than 1- and 2-year drug survival rates of systemic immunosuppressants (including cyclosporine [37% and 20%, respectively] and methotrexate [41% and 33%, respectively]). Overall, real-world data on drug survival have confirmed that dupilumab provides long-term sustained efficacy and acceptable safety in patients with moderate-to-severe AD.

Introduction: While the economic and clinical burden of chronic diseases are well documented, their environmental impact remains poorly understood. We developed a framework to estimate the environmental impact of a disease care pathway using chronic kidney disease (CKD) as an example.

Methods: A life cycle assessment framework was developed for the CKD care pathway and validated by experts. Life cycle stages were characterised for resource utilisation based on a literature review and ecoinvent database inputs, in ten countries. The ReCiPe impact assessment method was used to calculate impacts across multiple environmental dimensions.

Results: At CKD stage 5, kidney replacement therapies (KRT) have highest impact; emissions ranged between 3.5 and 43.9 kg carbon dioxide equivalents (CO₂e) per session depending on dialysis modality, and 336-2022 kg CO₂e for kidney transplant surgery, depending on donor type. Hospitalisations have a substantial environmental impact: a 1-day intensive care stay had highest impact (66.4-143.6 kg CO₂e), followed by a 1-day hospital stay (28.8-63.9 kg CO₂e) and an 8-h emergency room visit (14.4-27.5  kg CO₂e). Patient transport to and from healthcare sites was a key driver of environmental impact for all life cycle stages, representing up to 99.5% of total CO₂e emissions.

Conclusion: Full care pathways should be analysed alongside specific healthcare processes. Application of this framework enables quantification of the environmental benefits of preventative medicine and effective management of chronic diseases. For CKD, early diagnosis, and proactive management to reduce the need for KRT and hospitalisations could improve patient outcomes and reduce environmental burden.

Childhood obesity is a significant global health challenge with rising prevalence over the past 50 years, affecting both immediate and long-term health outcomes. The increase in prevalence from 0.7% to 5.6% in girls and 0.9% to 7.8% in boys highlights the urgency of addressing this epidemic. By 2025, it is estimated that 206 million children and adolescents aged 5-19 years will be living with obesity. This review explores the complex interplay of genomics and genetics in pediatric obesity, transitioning from monogenic and polygenic obesity to epigenetics, and incorporating advancements in omics technologies. The evolutionary purpose of adiposity, systemic evaluation of hyperphagia, and the role of various genetic factors are discussed. Technological advancements in genotyping offer new insights and interventions. The integration of genetic screening into clinical practice for early identification and personalized treatment strategies is emphasized.

Introduction: In China, approximately 2.3 million people have psoriasis. Continuous treatment is recommended for moderate-to-severe psoriasis. This study aimed to evaluate the outcomes of continuous versus interrupted ixekizumab (IXE) treatment and retreatment with IXE after disease worsening in Chinese patients.

Methods: In this Phase 3, multicenter, randomized, double-blind, placebo-controlled study, patients were randomized to IXE or placebo at Week 0. At Week 12, IXE responders (static Physician's Global Assessment [sPGA] score, 0 or 1 [0,1]) were re-randomized (2:1) to IXE (IXE/IXE, continuous treatment) or placebo (IXE/PBO, interrupted treatment). After re-randomization, treatment in IXE/PBO patients with disease worsening (relapse, sPGA ≥ 3) was switched to IXE every 4 weeks (IXE/PBO + IXEQ4W, retreatment). Efficacy was assessed by evaluating the response rates of Psoriasis Area and Severity Index (PASI) 75/90/100, sPGA (0,1), Dermatology Life Quality Index (DLQI) (0,1), mean PASI, and Itch Numerical Rating Scale (NRS) scores and improvements of special body areas. Safety was evaluated by assessing treatment-emergent adverse events (AEs) and serious AEs.

Results: At Week 12, 289 IXE responders were re-randomized to the IXE/IXE group (192 patients) and IXE/PBO group (97 patients). High rates of PASI 75 and sPGA (0, 1) responses were maintained in the IXE/IXE group until Week 60. At Week 60, 88 (90.7%) patients in the IXE/PBO group had disease relapse; the median time to relapse was approximately 20 weeks. After 24 weeks of retreatment, PASI 75 and sPGA (0, 1) were recaptured (97.2% and 74.6%, respectively, in the IXE/PBO + IXEQ4W group). AEs were comparable in patients who received continuous treatment and retreatment.

Conclusion: In Chinese patients who received continuous IXE treatment, high response rates were maintained through 60 weeks. Most patients had disease relapse after treatment withdrawal. After retreatment, most of these patients had regained and maintained response since Week 12.

Trial registration number: NCT03364309.

Introduction: In 2021, breast cancer affected 75,619 women in Denmark. Approximately 50% of breast cancers are considered human epidermal growth factor receptor 2 (HER2)-low. The DESTINY-Breast04 (DB-04) trial led to European Medicines Agency (EMA) approval of trastuzumab deruxtecan (T-DXd) as a treatment for patients with unresectable or metastatic HER2-low breast cancer who have received prior chemotherapy in the metastatic setting or developed disease recurrence during or within 6 months of completing adjuvant chemotherapy. Moreover, the Danish Breast Cancer Group guidelines recently included T-DXd as a treatment for HER2-low metastatic breast cancer. This economic evaluation aims to estimate the cost-effectiveness of T-DXd for the approved EMA indication in Denmark.

Methods: A three-state-progression-free, post-progression, and death-partitioned survival model was developed to estimate the cost-effectiveness of T-DXd versus treatment of physician's choice over a lifetime horizon following the Danish Medicines Council guidelines. Clinical data were gathered from the DB-04 trial, and cost and resource use data were sourced from the literature. Sensitivity and scenario analysis were conducted to explore uncertainty.

Results: T-DXd led to 0.78 incremental quality-adjusted life years (QALYs) gained and incurred DKK 621,325 in incremental costs compared to the treatment of physician's choice. This resulted in an incremental cost-effectiveness ratio of DKK 795,181 per QALY gained, which falls below the willingness-to-pay threshold. Sensitivity and scenario analyses showed the robustness of the deterministic result, with T-DXd remaining cost-effective.

Conclusion: Our study demonstrates that T-DXd is a cost-effective treatment for patients with HER2-low unresectable or metastatic breast cancer who have received prior chemotherapy in Denmark.

Introduction: Indirect treatment comparisons (ITCs) evaluate novel treatments compared to appropriate comparators when direct evidence is unavailable or infeasible. The objective of this study was to highlight the prevalence of different ITC methods in oncology drug submissions and to provide insights into how ITCs have been used in recent regulatory approval, reimbursement recommendations, or pricing decisions across various regions and diverse assessment frameworks.

Methods: A targeted literature review was conducted to identify assessment documents for oncology drug submissions that included ITCs. This included hand searches of the websites of four regulatory bodies and four health technology assessment (HTA) agencies with varying assessment frameworks across North America, Europe, and Asia-Pacific.

Results: A total of 185 documents were included for synthesis. Documents were retrieved from all four HTA agencies and the European Medicines Agency (EMA), the only regulatory body with eligible records. Within these, 188 unique submissions included a total of 306 supporting ITCs of various methods. Authorities more frequently favored anchored or population-adjusted ITC techniques for their effectiveness in data adjustment and bias mitigation. Furthermore, ITCs in orphan drug submissions more frequently led to positive decisions compared to non-orphan submissions.

Conclusions: This review highlights the crucial role and widespread use of ITCs in global healthcare decision-making, particularly when direct evidence is lacking, and in the discernment of market-specific clinical benefits. This work contributes to bolstering the credibility and recognition of ITCs across regulatory and HTA agencies of diverse regions and assessment frameworks.