Current treatments for the management of homozygous familial hypercholesterolemia: a systematic review and commentary.

AIMS: Homozygous familial hypercholesterolemia (HoFH) is a rare disorder characterized by markedly elevated circulating low-density lipoprotein cholesterol (LDL-C) from birth. This review aimed to critically evaluate treatments for HoFH with respect to their efficacy, safety, accessibility, overall context and position within the treatment pathway. METHODS: A mixed-methods review was undertaken to systematically identify and characterize primary interventional studies on HoFH, with a focus on LDL-C reduction as the primary outcome. Interventions assessed were ezetimibe, proprotein convertase subtilisin/kexin type 9 inhibitors (PCSK9i), lomitapide, evinacumab, with or without LDL apheresis. RESULTS: Twenty-six seminal studies reporting unique patient data were identified. Four studies were randomized controlled trials (RCTs) with the remainder being single-arm trials or observational registries. Data extracted were heterogeneous and not suitable for meta-analyses. Two RCTs, assessed at being low risk of bias, demonstrated PCSK9i were safe and moderately effective. An RCT demonstrated evinacumab was safe and effective in all HoFH subgroups. Lomitapide was reported to be efficacious in a single-arm trial, but issues with adverse events, tolerability, and adherence were identified. An RCT on ezetimibe showed it was moderately effective when combined with a statin. LDL apheresis was reported as effective, but its evidence base was at very high risk of bias. All interventions lowered LDL-C, but the magnitude of this, and certainty in the supporting evidence, varied. CONCLUSION: In practice, multiple treatments are required to treat HoFH. The sequencing of these should be made on an individualized basis, with consideration made to the benefits of each intervention.

Homozygous familial hypercholesterolaemia (HoFH) is a rare genetic disorder that results in elevated cholesterol levels, which can cause premature cardiovascular events such as heart attacks and stroke. We performed a literature review to systematically identify and analyse studies reporting on newer treatments for HoFH which lower cholesterol levels, focussing on the overall advantages and disadvantages of each treatment. We identified 26 studies, including clinical trials and observational research, reporting on the interventions ezetimibe, proprotein convertase subtilisin/kexin type 9 inhibitors (PCSK9i), lomitapide, evinacumab, and LDL apheresis. While all treatments showed promise in reducing cholesterol levels, none were sufficient to effectively treat HoFH on their own, and often the confidence in the results were limited by the methodological weaknesses of the studies. The evidence suggests that management of HoFH requires an individualized approach, with consideration given to the efficacy, safety, tolerability and accessibility of each treatment.

Reverse causation between multiple sclerosis and psoriasis: a genetic correlation and Mendelian randomization study.

Observational studies have found a potential bidirectional positive association between multiple sclerosis and psoriasis, but these studies are susceptible to confounding factors. We examined the directionality of causation using Mendelian randomization and estimated the genetic correlation using the linkage disequilibrium score. We performed Mendelian randomization analysis using large-scale genome-wide association studies datasets from the International Multiple Sclerosis Genetics Consortium (IMSGC, 115,803 individuals of European ancestry) and FinnGen (252,323 individuals of European ancestry). We selected several Mendelian randomization methods including causal analysis using summary effect (CAUSE), inverse variance-weighted (IVW), and pleiotropy-robust methods. According to CAUSE and IVW the genetic liability to MS reduces the risk of psoriasis (CAUSE odds ratio [OR] 0.93, p = 0.045; IVW OR 0.93, p = 2.51 × 10-20), and vice versa (CAUSE OR 0.72, p = 0.001; IVW OR 0.71, p = 4.80 × 10-26). Pleiotropy-robust methods show the same results, with all p-values < 0.05. The linkage disequilibrium score showed no genetic correlation between psoriasis and MS (rg = - 0.071, p = 0.2852). In summary, there is genetic evidence that MS reduces the risk of psoriasis, and vice versa.

Elevated gut microbiota metabolite bile acids confer protective effects on clinical prognosis in ischemic stroke patients.

Background: There is evidence of an association between the gut microbiota and progression of stroke. However, the relationship between gut microbial metabolites, specifically bile acids (BAs), and post-ischemic stroke disability and poor functional outcomes remains unexplored. Methods: Patients with acute ischemic stroke (AIS) or transient ischemic attack (TIA) in the Third China National Stroke Registry were grouped according to total bile acid (TBA) quartile on admission. Association of TBA with disability and poor functional outcomes were evaluated using logistic regression models and restricted cubic splines. Results: Data for 9,536 patients were included. After adjusting for confounders, the risks of disability and poor functional outcomes were significantly lower in the highest TBA quartile than in the lowest TBA quartile at the 3-month follow-up, with respective odds ratios (ORs) of 0.65 (95% confidence interval [CI] 0.55-0.78; p < 0.001) and 0.66 (95% CI 0.55-0.78, p < 0.001). Each standard deviation increase in the TBA level reduced the risks of disability and poor functioning outcomes by 10% (adjusted ORs 0.9 [95% CI 0.83-0.98; p = 0.01] and 0.9 [95% CI 0.83-0.97; p < 0.001], respectively). This association remained similar at the 1-year follow-up. After stratification by TOAST subtype, the risk of disability or a poor functional outcome in patients with the large-artery atherosclerosis or "other" subtype was significantly lower in the highest quartile than in the lowest quartile (p < 0.05). Conclusion: Serum TBA is an independent risk factor for disability and poor functional outcomes after AIS or TIA, and exerts a protective effects on brain.

How dyadic appraisal moderate the association between dyadic coping and diabetes management efficacy.

To explore the moderating role of dyadic appraisal in the association between dyadic coping and diabetes management efficacy. Two hundred seventy six middle-aged and older couple pairs with one spouse who had diabetes were recruited from 14 community healthcare centers across Guangzhou. The moderating role of dyadic appraisal was investigated using the actor-partner interdependence moderation model. When both couples considered diabetes to be a shared condition, statistically-significant associations were found between patients' negative (ß = -22.7, p = 0.008) and neutral behaviors (ß = 13.6, p = 0.017), plus spouses' positive behaviors (ß = 22.8, p = 0.009) on their own diabetes management efficacy, respectively (i.e. actor effects); as well as between spouses' positive (ß = 16.8, p = 0.028), negative (ß = -28.5, p < 0.001), and neutral behaviors (ß = 16.9, p = 0.006) on patient's diabetes management efficacy (i.e. partner effects). Dyadic appraisal moderates the association between dyadic coping and diabetes management efficacy.

Unraveling the contributing factors of stale odor in Longjing tea through a sensomics approach.

Longjing tea is renowned for its fresh aroma and high value. However, during storage, the emergence of an off-flavor known as "stale odor" can significantly impact the flavor quality and economic benefits of Longjing tea. Yet, the specific volatiles responsible for this stale odor in Longjing tea remain unknown. In this study, Longjing tea samples with varying degrees of stale odor intensity were analyzed using simultaneous distillation extraction coupled with gas chromatography-mass spectrometry (SDE-GC-MS). Through odor activity value (OAV) and fractional omission testing, hexanoic acid and trans-2-nonenal were identified as the primary contributors to the stale odor. Moreover, the concentration of hexanoic acid was found to be valuable in predicting the intensity of the stale odor in Longjing tea. The oxidative degradation of linoleic acid was proved as the generation pathway of stale odor in Longjing tea. These findings provide essential theoretical principles for Longjing tea production and preservation.

Global scientific trends in healthy aging in the early 21st century: A data-driven scientometric and visualized analysis.

Background: According to the World Health Organization (WHO), healthy aging is the process of developing and maintaining the functional capacity for health in old age. A rapidly growing number of research studies on healthy aging have been conducted worldwide. The purpose of this research work is to explore global scientific landscape of healthy aging research over the last 22 years. Methods: Scientific publications on healthy aging from January 1, 2000 to October 11, 2022 were retrieved from the Web of Science Core Collection (WoSCC) on October 11, 2022. A total of 6420 publications were included in the scientometric analysis. VOSviewer (1.6.18) was used to conduct scientometric and visualized analysis. Results: The publication growth rate was 35.68 from 2000 to 2021. The United States of America (USA) led in both productivity and citations. PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA was prominent in terms of both the highest citation count and the highest average citation count. The National Institute on Aging (NIA) and Evans, Michele K. were the most influential organization and author, respectively. Research hotspots in healthy aging were identified based on the co-occurrence analysis of keywords: (1) physical activity and mental health of older adults; (2) diseases impacting the health and lifespan of older adults; and (3) neuroscience. Our analysis indicates that gut microbiota, loneliness, frailty, mitochondria and resilience were the emerging themes in healthy aging research. Conclusions: The quantity of annual publications on healthy aging has rapidly increased over the past 22 years, especially during 2018-2021. This analysis identified the status, trends, hot topics, and frontiers of healthy aging research. These findings will help researchers quickly understand the global representation of healthy aging research, influence resource dissemination, promote international collaborations, guide policy formulation, and improve health services for older adults.

Development and Validation of Multi-Omics Thymoma Risk Classification Model Based on Transfer Learning.

The paper aims to develop prediction model that integrates clinical, radiomics, and deep features using transfer learning to stratifying between high and low risk of thymoma. Our study enrolled 150 patients with thymoma (76 low-risk and 74 high-risk) who underwent surgical resection and pathologically confirmed in Shengjing Hospital of China Medical University from January 2018 to December 2020. The training cohort consisted of 120 patients (80%) and the test cohort consisted of 30 patients (20%). The 2590 radiomics and 192 deep features from non-enhanced, arterial, and venous phase CT images were extracted and ANOVA, Pearson correlation coefficient, PCA, and LASSO were used to select the most significant features. A fusion model that integrated clinical, radiomics, and deep features was developed with SVM classifiers to predict the risk level of thymoma, and accuracy, sensitivity, specificity, ROC curves, and AUC were applied to evaluate the classification model. In both the training and test cohorts, the fusion model demonstrated better performance in stratifying high and low risk of thymoma. It had AUCs of 0.99 and 0.95, and an accuracy of 0.93 and 0.83, respectively. This was compared to the clinical model (AUCs of 0.70 and 0.51, accuracy of 0.68 and 0.47), the radiomics model (AUCs of 0.97 and 0.82, accuracy of 0.93 and 0.80), and the deep model (AUCs of 0.94 and 0.85, accuracy of 0.88 and 0.80). The fusion model integrating clinical, radiomics and deep features based on transfer learning was efficient for noninvasively stratifying high risk and low risk of thymoma. The models could help to determine surgery strategy for thymoma cancer.

Cannabidiol regulates apoptosis and autophagy in inflammation and cancer: A review.

Cannabidiol (CBD) is a terpenoid naturally found in plants. The purified compound is used in the treatment of mental disorders because of its antidepressive, anxiolytic, and antiepileptic effects. CBD can affect the regulation of several pathophysiologic processes, including autophagy, cytokine secretion, apoptosis, and innate and adaptive immune responses. However, several authors have reported contradictory findings concerning the magnitude and direction of CBD-mediated effects. For example, CBD treatment can increase, decrease, or have no significant effect on autophagy and apoptosis. These variable results can be attributed to the differences in the biological models, cell types, and CBD concentration used in these studies. This review focuses on the mechanism of regulation of autophagy and apoptosis in inflammatory response and cancer by CBD. Further, we broadly elaborated on the prospects of using CBD as an anti-inflammatory agent and in cancer therapy in the future.

Recent Advances in Animal Models, Diagnosis, and Treatment of Temporomandibular Joint Osteoarthritis.

Temporomandibular joint osteoarthritis (TMJOA) is a gradual degenerative jaw joint condition. Until recent years, TMJOA is still relatively unrecognized and ineffective to be treated. Appropriate animal models with reliable detection methods can help researchers understand the pathophysiology of TMJOA and find therapeutic options. In this study, we summarized common animal models of TMJOA created by chemical, surgical, mechanical, and genetical approaches. The relevant pathological symptoms and induction mechanisms were outlined. In addition, different pathological indicators, furthermore, emerging therapeutic regimens, such as intra-articular drug delivery and tissue engineering-based approaches to treat TMJOA based on these animal models, were summarized and updated. Understanding the physiology and pathogenesis of the TMJOA, together using various ways to diagnose the TMJOA, were elaborated, including imaging techniques, molecular techniques for detecting inflammatory cytokines, histochemical staining, and histomorphometry measures. A more reliable diagnosis will enable the development of new prevention and more effective treatment strategies and thereby improve the quality of life of TMJOA patients. Impact statement Temporomandibular joint osteoarthritis (TMJOA) affects 8 to 16 percent of the population worldwide. However, TMJOA is still relatively unrecognized and ineffective to be treated in the clinic. Appropriate animal models with reliable diagnostic methods can help researchers understand the pathophysiology of TMJOA and find therapeutic options. We herein summarized common animal models of TMJOA and various ways to diagnose the TMJOA. More importantly, emerging therapeutic regimens to treat TMJOA based on these animal models were summarized. With the aid of strategies listed, more effective treatment strategies will be developed and thereby improve the life quality of TMJOA patients.

Gender-Specific Effect of Couple-Based Intervention on Behavioral and Psychological Outcomes of Older Adults with Type 2 Diabetes during the COVID-19 Partial Lockdown in Guangzhou, China.

This study aimed to evaluate the gender-specific effect of a couple-based intervention on the management behaviors and mental well-being of community-dwelling older adults with type 2 diabetes mellitus during the COVID-19 partial lockdown in Guangzhou. Out of 207 participants involved in a prior randomized controlled trial (Trial no. ChiCTR1900027137), 156 (75%) completed the COVID-19 survey. Gendered differences in management behaviors and depressive symptoms between the couple-based intervention group and the patient-only control group were compared by distance to the high-risk areas cross-sectionally and longitudinally using random intercept models. Cross-sectionally, female patients of the intervention group had more positive behavior change scores (ß = 1.53, p = 0.002) and fewer depressive symptoms (ß = −1.34, p = 0.02) than the control group. Over time, female patients lived closer to the high-risk areas (<5 km) and showed decreasing depressive symptoms (ß = −4.48, p = 0.008) in the intervention group vs. the control group. No statistically significant between-group difference was found for males. Females tended to benefit more from the coupled-based intervention than males did, particularly among these closer to the high-risk areas. Chronic disease management can be better sustained with active spousal engagement.

Global trends in smoking cessation research from 2002 to 2021: A bibliometric and visual analysis.

This study aimed to analyze the scientific outputs of smoking cessation research and explore its hotspots and frontiers from 2002 to 2021, using bibliometric methods. We use the core collection of Web of Science as a data source, and apply bibliometric methods to visually analyze articles published in smoking cessation research from 2002 to 2021, including publication year, countries/regions, journals, authors, institutions, and keywords. The VOSviewer (1.6.16) tool was used for the analysis. A total of 8797 articles related to smoking cessation research were identified. The USA was the leading contributor with 4671 publications. NICOTINE＆TOBACCO RESEARCH contributed the most publications (528), with the most citations (13746) and the highest H-index (59). The most contributing institutions were the University College London and University of California San Francisco. Robert West was most productive author. We found active collaborations among both productive authors and productive institutions. There were five hot topics in smoking cessation research: (1) Public health harm from tobacco; (2) The role of e-health in smoking cessation; (3) Role of primary health care in eliminating tobacco dependence; (4) Nicotine replacement therapy and pharmacotherapy; (5) The biological and clinical understanding of addiction. Our current study showed a growing trend in smoking cessation based on the number of published articles over the last 20 years. There was active cooperation between institutions, and authors. Electronic cigarettes, mHealth, eHealth, public health and mental health are foci of new and emerging research.

Integrated analysis of intestinal microbiota and host gene expression in colorectal cancer patients.

Introduction. Colorectal cancer (CRC) is one of the most common cancers and poses heavy burden on global health. The relationship between mucosal microbiome composition and colorectal gene expression are rarely studied. In this study, we integrated transcriptome data with microbiome data to investigate the relationship between them in colorectal cancer patients.Gap statement. Previous studies have identified the contribution of gut microbiota and DEGs to the pathogenesis of CRC, but the relationship between mucosal microbiome composition and colorectal gene expression are rarely studied.Aim. In this study, we integrated transcriptome data with microbiome data to investigate the relationship between mucosal microbiome composition and colorectal gene expression.Methodology. First, three independent CRC gene expression profiles (GSE184093, GSE156355 and GSE146587) from Gene Expression Omnibus (GEO) were used to identify differentially expressed genes (DEGs). Second, another dataset (GSE163366) was used to analyse gut mucosal microbiome differential abundance. GO (Gene Ontology) function and KEGG (Kyoto Encyclopaedia of Genes and Genomes) pathway enrichment analyses of the DEGs were performed. Protein-protein interactions (PPIs) of the DEGs were constructed. The Spearman correlation analysis was computed between host DEGs and gut microbiome abundance data.Results. A total of 1036 upregulated DEGs and 1194 downregulated DEGs between noncancerous tissues and cancerous tissues were identified based on the analysis. One significant module with a score 37.65 was selected out via MCODE including 41 upregulated DEGs, which are were mostly enriched in two pathways, including microtubule binding and tubulin binding. In particular, significant negative correlations are prevalent between Fusobacterium and the 41 DEGs with the correlation ranging between -0.54 and -0.35, and there commonly exist significant positive correlations between Blautia and the 41 DEGs with the correlation ranging between 0.42 and 0.54, indicating that Fusobacterium and Blautia are two of the most important microbes interacting with the gene regulation.Conclusion. Our results demonstrate significant correlation between some gut microbes and DEGs, providing a comprehensive bioinformatics analysis of them for future investigation into the molecular mechanisms and biomarkers.

Oral Health Self-Management Ability and Its Influencing Factors among Adolescents with Fixed Orthodontics in China: A Mixed Methods Study.

Objective: To understand the oral health self-management ability status and influencing factors among adolescent patients with fixed orthodontics in Nanjing and to provide a reference for formulating targeted intervention measures. Methods: A mixed research method was used. First, the convenience sampling method was used to select adolescent patients with fixed orthodontics admitted to the orthodontic department of a dental hospital in Nanjing from November 2021 to March 2022. The oral health self-management ability questionnaire was used for the investigation; then, 15 children with poor oral health management ability were selected for in-depth interviews. Results: The total score of oral health self-management ability of 290 adolescent children with fixed orthodontics was 45.6-90.8 points, with an average score of 69.63 ± 7.40 of which knowledge, belief, and behavior dimension scores were 72.09 ± 10.47, 68.50 ± 10.13, and 67.63 ± 8.67, respectively, and the environmental score was 69.91 ± 12.50. Multiple regression analysis showed that sex, age, bracket wearing time, grade, and place of residence were related to the scores of each dimension of self-management. Qualitative research shows that the main reasons for the poor oral health self-management ability of adolescents with fixed orthodontics are the lack of awareness during fixed orthodontics, lack of knowledge channels, low compliance, inability to solve oral problems during treatment, difficulty in adhering to oral care behaviors, and lack of motivation to treat. Conclusion: The oral health self-management ability of adolescent children with fixed orthodontics needs improvement, and a precise health intervention plan should be formulated.

Global scientific trends on the immunomodulation of mesenchymal stem cells in the 21st century: A bibliometric and visualized analysis.

Background: Since the discovery of the immunomodulatory functions of mesenchymal stem cells (MSCs), their application in immunomodulation has attracted considerable attention, and an increasing number of studies have been conducted worldwide. Our research aimed to investigate the global status and trends in this field. Methods: Publications on the immunomodulatory functions of MSCs from 1 January 2000 to 7 March 2022 were retrieved from the Web of Science Core Collection. The data were studied and indexed using the bibliometric methodology. Visualization analysis, co-authorship, co-occurrence analysis, and publication trends in MSC immunomodulation were conducted using the VOSviewer software. Results: In total, 4,227 papers were included in the study. The number of publications and research interests has significantly increased globally. China published the highest number of related articles, while the US published articles with the highest number of citations. Stem Cell Research & Therapy had the highest number of publications. Sun Yat-sen University, Shanghai Jiao Tong University, Harvard University, and Seoul National University were the most contributive institutions. Furthermore, the studies were divided into four research hotspots for MSC immunomodulation: MSC immunomodulation in regenerative medicine, the effects and mechanisms of MSC immunomodulation, MSC therapy for immune diseases, and the cell source of MSCs. Conclusion: This study indicates that the number of publications on MSC immunomodulation will increase in the future, and MSC immunomodulation mechanisms and clinical applications of MSC immunotherapy should be the next hotspots in this research field.

Network meta-analysis of immune-oncology monotherapy as first-line treatment for advanced non-small-cell lung cancer in patients with PD-L1 expression ⩾50.

Background: For patients with advanced non-small-cell lung cancer (NSCLC) and high (⩾50%) programmed cell death-ligand 1 (PD-L1) expression, effective first-line immune-oncology monotherapies with significant survival benefits are approved, cemiplimab being the most recent. In a phase III trial, cemiplimab demonstrated significantly improved overall survival (OS) and progression-free survival (PFS) versus chemotherapy in patients with advanced NSCLC and PD-L1 ⩾50%. A systematic literature review and network meta-analysis (NMA) was conducted to identify/compare the efficacy/safety of cemiplimab versus pembrolizumab or other immune-oncology monotherapies from randomized-controlled trials (RCTs) published in November 2010-2020. Methods: Relevant RCTs were identified by searching databases and conference proceedings as per ISPOR, NICE, and Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. NMA with time-varying hazard ratios (HRs) was performed for OS and PFS. Analyses were conducted for objective response rate (ORR) and safety/tolerability. Fixed-effect models were used due to limited evidence. Various sensitivity analyses were conducted to validate the base case analyses. Results: The feasibility assessment determined that EMPOWER-Lung 1, KEYNOTE-024, and KEYNOTE-042 trials were eligible. IMpower110 was excluded because an incompatible PD-L1 assay (SP142) was used for patient selection. For first-line advanced NSCLC with PD-L1 ⩾50%, cemiplimab was associated with statistically significant improvements in PFS [HR (95% credible interval [CrI]): 0.65 (0.50-0.86), 1-12 months] and ORR [odds ratio (OR) (95% CrI): 1.64 (1.04-2.62)], and comparable OS [HR (95% CrI): 0.77 (0.54-1.10), 1-12 months] versus pembrolizumab. There was no evidence of differences between cemiplimab and pembrolizumab for Grade 3-5 adverse events (AEs) [OR (95% CrI): 1.47 (0.83-2.60)], immune-mediated AEs [1.75 (0.33-7.49)], and all-cause discontinuation due to AEs [1.21 (0.58-2.61)]. Conclusions: Considering the limitations of indirect treatment comparisons, in patients with advanced NSCLC and PD-L1 ⩾50%, cemiplimab monotherapy demonstrated significant improvements in PFS and ORR, comparable OS, and no evidence of differences in safety/tolerability versus pembrolizumab.

Global Scientific Research Landscape on Medical Informatics From 2011 to 2020: Bibliometric Analysis.

BACKGROUND: With the emerging information and communication technology, the field of medical informatics has dramatically evolved in health care and medicine. Thus, it is crucial to explore the global scientific research landscape on medical informatics. OBJECTIVE: This study aims to present a visual form to clarify the overall scientific research trends of medical informatics in the past decade. METHODS: A bibliometric analysis of data retrieved and extracted from the Web of Science Core Collection (WoSCC) database was performed to analyze global scientific research trends on medical informatics, including publication year, journals, authors, institutions, countries/regions, references, and keywords, from January 1, 2011, to December 31, 2020. RESULTS: The data set recorded 34,742 articles related to medical informatics from WoSCC between 2011 and 2020. The annual global publications increased by 193.86% from 1987 in 2011 to 5839 in 2020. Journal of Medical Internet Research (3600 publications and 63,932 citations) was the most productive and most highly cited journal in the field of medical informatics. David W Bates (99 publications), Harvard University (1161 publications), and the United States (12,927 publications) were the most productive author, institution, and country, respectively. The co-occurrence cluster analysis of high-frequency author keywords formed 4 clusters: (1) artificial intelligence in health care and medicine; (2) mobile health; (3) implementation and evaluation of electronic health records; (4) medical informatics technology application in public health. COVID-19, which ranked third in 2020, was the emerging theme of medical informatics. CONCLUSIONS: We summarize the recent advances in medical informatics in the past decade and shed light on their publication trends, influential journals, global collaboration patterns, basic knowledge, research hotspots, and theme evolution through bibliometric analysis and visualization maps. These findings will accurately and quickly grasp the research trends and provide valuable guidance for future medical informatics research.

Cost-Effectiveness of Cemiplimab Versus Standard of Care in the United States for First-Line Treatment of Advanced Non-small Cell Lung Cancer With Programmed Death-Ligand 1 Expression ≥50.

OBJECTIVES: This study aimed to evaluate the cost-effectiveness, from a US commercial payer perspective, of cemiplimab versus other first-line treatments for advanced non-small cell lung cancer with programmed death-ligand 1 expression ≥50%. METHODS: A 30-year "partitioned survival" model was constructed. Overall survival and progression-free survival were estimated by applying time-varying hazard ratios from a network meta-analysis of randomized clinical trials. Overall survival and progression-free survival were estimated from EMPOWER-Lung 1 (cemiplimab monotherapy vs chemotherapy) and KEYNOTE-024 and KEYNOTE-042 (pembrolizumab monotherapy vs chemotherapy). Drug acquisition costs were based on published 2020 US list prices. A 3% discount rate was applied to life-years, quality-adjusted life-years (QALYs), and costs. A deterministic analysis was performed on the base case; 1-way sensitivity and probabilistic sensitivity analyses assessed model and parameter uncertainties. RESULTS: Cemiplimab was associated with increased time in the "preprogression" (13.08 vs 7.90 and 6.08 months) and "postprogression" (47.30 vs 29.49 and 14.78 months) health states versus pembrolizumab and chemotherapy, respectively. Compared with pembrolizumab and chemotherapy, cemiplimab generated 1.00 (95% CI -0.266 to 2.440) and 1.78 (95% CI 0.607-3.20) incremental QALYs, respectively, with incremental cost-effectiveness ratios of $68 254 and $89 219 per QALY for cemiplimab versus pembrolizumab and cemiplimab versus chemotherapy, respectively. The probability of cemiplimab being cost-effective at a willingness-to-pay threshold of $100 000 to $150 000 per QALY was 62% to 76% versus pembrolizumab and 56% to 84% versus chemotherapy. CONCLUSIONS: Findings suggest that cemiplimab, versus pembrolizumab or versus chemotherapy, is a cost-effective first-line treatment option for advanced non-small cell lung cancer with programmed death-ligand 1 expression ≥50%.

Pairwise indirect treatment comparison of dupilumab versus other biologics in patients with uncontrolled persistent asthma.

BACKGROUND: Currently, five biologic treatment options are available for use in patients with uncontrolled persistent asthma: three interleukin (IL)-5 antagonists, which either bind to the anti-IL-5 ligand (mepolizumab, reslizumab) or to the IL-5 receptor (benralizumab); one anti-immunoglobulin E (anti-IgE) therapy (omalizumab); and one anti-IL-4/IL-13 therapy (dupilumab). To date, no comparative data from head-to-head clinical trials are available for these biologics. OBJECTIVE: An indirect treatment comparison (ITC) of dupilumab versus each of the anti-IL-5 and anti-IgE therapies using the endpoints of annualized severe asthma exacerbation rates and change in pre-bronchodilator forced expiratory volume in 1 s (FEV1). METHODS: Embase®, MEDLINE®, and Cochrane Central Register of Controlled Trials (CENTRAL) were searched for studies published between January 1, 1980 and March 25, 2019. Eligible articles included randomized controlled trials (RCTs) in patients aged ≥ 12 years with persistent/uncontrolled asthma using at least medium-to-high dose inhaled corticosteroid plus long-acting ß2-agonist with add-on biologic therapy. Bucher ITCs were performed to compare subgroups of dupilumab patients with the anti-IL-5s and anti-IgE trial populations. RESULTS: Fourteen RCTs were included in the analyses. The matched dupilumab subgroups were associated with greater reductions in annualized severe exacerbation rates compared with benralizumab, mepolizumab, reslizumab, and omalizumab (54%, 28%, 38%, and 26% greater reduction, respectively). A greater improvement in FEV1 was also observed for dupilumab at week 12 and/or week 24/52 than for the other biologics (0.06-0.14 L). CONCLUSION: In this ITC, dupilumab was associated with lower severe asthma exacerbation rates and greater improvements in lung function than anti-IL-5s and omalizumab.