The humanistic and societal impact of obesity in Japan: a targeted literature review.

Obesity is a focus of Japanese public health policy, due to Japanese individuals' high susceptibility to weight-related conditions. In contrast to global definitions, obesity is defined as a body-mass-index (BMI) of ≥25 kg/m2 in Japan. Despite public efforts, rates of obesity have not decreased over the past decade. To better understand its societal impact, we examined the economic, quality of life (QoL), and complications burden of obesity in Japan. Electronic databases were searched for English and Japanese-language publications from 2005 to December 2020 reporting on adults with obesity in Japan; other diseases were excluded, with no restriction on intervention. Outcomes of interest included costs or resource use, QoL, risk of complications, and other clinical outcomes. We identified 137 studies, including 19 reporting on economic evidence, eight reporting on QoL, and 115 reporting on the relationship between obesity and the risk of complications or mortality. The studies consistently showed that Japanese adults with obesity (BMI ≥25 kg/m2) are at increased risk of complications vs. normal weight adults. They also confirmed higher total and medical costs, resource use, and hospitalization costs among adults with obesity vs. normal weight adults. In addition, the studies confirmed a considerable impact of obesity on physical and mental aspects of QoL. Overall, this study found that obesity in Japan is associated with a substantial burden. Japanese people are at risk even with BMI ≥25-<30 kg/m2, which are generally considered as pre-obese in other countries.

Once-Daily Oral Semaglutide Versus Injectable GLP-1 RAs in People with Type 2 Diabetes Inadequately Controlled on Basal Insulin: Systematic Review and Network Meta-analysis.

INTRODUCTION: The relative efficacy and safety of once-daily oral semaglutide vs. injectable glucagon-like peptide-1 receptor agonists (GLP-1 RAs) in subjects with type 2 diabetes (T2D) inadequately controlled on basal insulin were assessed using network meta-analysis (NMA). METHODS: A systematic literature review (SLR) was performed to identify randomised controlled trials of GLP-1 RAs in this population. Data at 26 ± 4 weeks were extracted for efficacy and safety outcomes feasible for the NMA: change from baseline in glycated haemoglobin (HbA1c), weight and blood pressure; HbA1c target levels (< 7.0% and ≤ 6.5%); composite endpoint; incidence of nausea, vomiting or diarrhoea. Comparators of interest were all licensed doses of dulaglutide, exenatide, liraglutide, lixisenatide and once-weekly injectable semaglutide. RESULTS: The NMA included seven trials. Once-daily oral semaglutide 14 mg was associated with significantly greater HbA1c reductions vs. most comparators (treatment differences: - 0.42 to - 1.32%); differences vs. once-weekly injectable semaglutide (0.5 mg and 1 mg doses) were not statistically significant. Once-daily oral semaglutide 14 mg was associated with significantly greater weight reductions vs. exenatide 2 mg and lixisenatide 20 µg (- 2.21 and - 2.39 kg respectively); non-statistically significant weight reductions in favour of once-daily oral semaglutide 14 mg were observed vs. all other comparators except once-weekly injectable semaglutide 1 mg. Similar trends were observed for the proportion of subjects achieving HbA1c < 7.0% and ≤ 6.5% and the composite endpoint. Once-daily oral semaglutide 14 mg was associated with similar odds of experiencing nausea, vomiting or diarrhoea vs. all comparators. CONCLUSION: Once-daily oral semaglutide 14 mg, as an add-on to basal insulin, is an efficacious treatment for reducing HbA1c and weight and meeting glycaemic targets at 26 ± 4 weeks. Once-daily oral semaglutide 14 mg also offers the option of an oral treatment with similar or better efficacy and similar tolerability vs. most injectable GLP-1 RAs.

A Systematic Review of the Clinical Efficacy of Treatments in Relapsed or Refractory Diffuse Large B Cell Lymphoma.

INTRODUCTION: Novel treatment options are needed to improve outcomes in transplant-ineligible relapsed/refractory (R/R) diffuse large B cell lymphoma (DLBCL). This systematic literature review evaluated clinical evidence on treatments for patients with R/R DLBCL ineligible for, or relapsed following, stem cell transplantation. METHODS: We assessed the feasibility of conducting an indirect treatment comparison (ITC) or network meta-analysis (NMA) to evaluate the relative efficacy and safety of polatuzumab vedotin in combination with bendamustine + rituximab versus other relevant treatments. RESULTS: Thirty-seven studies were identified, of which 20 were eligible [seven randomized, controlled trials (RCTs); 13 observational/single-arm trials]. Due to a lack of RCTs, an ITC/NMA summary of the relative efficacy and safety of the treatment options was not possible. Only two of the seven RCTs had positive outcomes. CONCLUSIONS: These findings highlight the paucity of published RCTs to establish the comparative efficacy of treatments for transplant-ineligible R/R DLBCL and lack of standard of care in this setting.

PD-L1 expression in advanced NSCLC: Insights into risk stratification and treatment selection from a systematic literature review.

Tumors can evade immune detection by exploiting inhibitory immune checkpoints such as the programmed cell death-1 (PD-1)/programmed cell death ligand-1 (PD-L1) pathway. Antibodies that block this pathway offer a promising new approach to treatment in advanced/metastatic non-small cell lung cancer (NSCLC). A systematic review of the literature was conducted to assess the association of PD-L1 with important patient and disease characteristics, the prognostic significance of PD-L1 expressing NSCLC tumors, and the value of PD-L1 as a predictive biomarker of response to anti-PD-1/PD-L1 treatments in advanced/metastatic NSCLC. A total of 35 eligible studies were selected for analysis. Methods used to determine PD-L1 in NSCLC tissue varied considerably; with different PD-L1 antibodies, antibody detection methods, and staining cut-offs. Immunohistochemistry was the most frequent type of PD-L1 assay. Overall, study evidence did not support an association between PD-L1 expression and gender, age, smoking history, tumor histology (adenocarcinoma vs. squamous cell carcinoma), performance status, pathologic tumor grade or EGFR/KRAS/ALK mutational status. In several studies, high PD-L1 expression was associated with shorter survival compared with low expression. Most evidence indicated that patients with high vs. low PD-L1 expression were more likely to experience treatment benefit with anti-PD-1/PD-L1 agents (nivolumab, pembrolizumab, durvalumab, atezolizumab, and avelumab) in advanced NSCLC. Variability in the methods used to determine PD-L1 expression in NSCLC tissue suggests a need for standardized use of well-validated PD-L1 diagnostic assays. Although considerable research links PD-L1 expression in tumors to shorter survival in advanced/metastatic NSCLC, its use as a prognostic factor requires more study. As studies of anti-PD-1/PD-L1 agents continue, PD-L1 is likely to play an important role as a predictive biomarker for selecting patients deriving most benefit from anti-PD-1/PD-L1 monotherapy and directing patients with lower levels of tumor PD-L1 expression (with a high unmet medical need), to alternative treatments, such as combination immunotherapies.