Eli Lilly (Germany)

Abstract Cell free DNA (cfDNA) analysis has a large potential for cancer patient diagnosis. Given the evidence that cfDNA partially preserves chromatin architecture of tumor cells, it potentially allows the detection of tumor responses after therapeutic treatment. In this study, we aimed to detect the responses of abemaciclib, a potent cyclin-dependent kinase 4 and 6 inhibitor (CDK4/6 inhibitor), in metastatic recurrent breast cancer patients through cfDNA analysis. Our results suggest that cfDNA can be used as a valuable marker to monitor cancer burden, cancer responses to drug treatment, and sensitivity against therapeutic reagents. CfDNA concentrations purified from serum are significantly higher in cancer patients compared to healthy donors, suggesting that a significant portion of the cfDNA originates from tumors in our samples. The cfDNA concentrations are also significantly decreased after abemaciclib treatment. The sequencing analysis of cfDNAs revealed a higher enrichment of cfDNAs at open chromatin regions and differentiated the cfDNA enrichment patterns between abemaciclib treated and non-treated samples. Altered cfDNA signals are frequently associated with the genes that are involved in apoptosis and CDK4/6 related pathways. Finally, the differentially enriched region analysis also detected the differences in abemaciclib cases that could be treated long-term and cases that had an exacerbation after short-term treatment. In conclusion, this research enhances our understanding of the biology of abemaciclib and provides new insights into CDK4/6 inhibitor’s action in metastatic breast cancer.

Limited evidence exists on the comparative safety and effectiveness of empagliflozin against alternative glucose-lowering medications in individuals with type 2 diabetes with the broad spectrum of cardiovascular risk. The EMPagliflozin compaRative effectIveness and SafEty (EMPRISE) cohort study was designed to monitor the safety and effectiveness of empagliflozin periodically for a period of 5 years with data collection from electronic healthcare databases. We identified individuals ≥18 years old with type 2 diabetes who initiated empagliflozin or dipeptidyl peptidase-4 inhibitors (DPP-4i) from 2014 to 2019 using US Medicare and commercial claims databases. After 1:1 propensity score matching using 143 baseline characteristics, we identified four a priori-defined effectiveness outcomes: (1) myocardial infarction (MI) or stroke; (2) hospitalisation for heart failure (HHF); (3) major adverse cardiovascular events (MACE); and (4) cardiovascular mortality or HHF. Safety outcomes included lower-limb amputations, non-vertebral fractures, diabetic ketoacidosis (DKA), acute kidney injury (AKI), severe hypoglycaemia, retinopathy progression, and short-term kidney and bladder cancers. We estimated HRs and rate differences (RDs) per 1000 person-years, overall and stratified by age, sex, baseline atherosclerotic cardiovascular disease (ASCVD) and heart failure. We identified 115,116 matched pairs. Compared with DPP-4i, empagliflozin was associated with lower risks of MI/stroke (HR 0.88 [95% CI 0.81, 0.96]; RD -2.08 [95% CI (-3.26, -0.90]), HHF (HR 0.50 [0.44, 0.56]; RD -5.35 [-6.22, -4.49]), MACE (HR 0.73 [0.62, 0.86]; RD -6.37 [-8.98, -3.77]) and cardiovascular mortality/HHF (HR 0.57 [0.47, 0.69]; RD -10.36 [-12.63, -8.12]). Absolute benefits were larger in older individuals and in those with ASCVD/heart failure. Empagliflozin was associated with an increased risk of DKA (HR 1.78 [1.44, 2.19]; RD 1.59 [1.08, 2.09]); decreased risks of AKI (HR 0.62 [0.54, 0.72]; RD -2.39 [-3.08, -1.71]), hypoglycaemia (HR 0.75 [0.67, 0.84]; RD -2.46 [-3.32, -1.60]) and retinopathy progression (HR 0.78 [0.63, 0.96)]; RD -9.49 [-16.97, -2.10]); and similar risks of other safety events. Empagliflozin relative to DPP-4i was associated with risk reductions of MI or stroke, HHF, MACE and the composite of cardiovascular mortality or HHF. Absolute risk reductions were larger in older individuals and in those who had history of ASCVD or heart failure. Regarding the safety outcomes, empagliflozin was associated with an increased risk of DKA and lower risks of AKI, hypoglycaemia and progression to proliferative retinopathy, with no difference in the short-term risks of lower-extremity amputation, non-vertebral fractures, kidney and renal pelvis cancer, and bladder cancer.

Introduction: Here, we present patient and HCP perspectives on the experiences and impact of Crohn’s disease (CD)-related symptoms from Communicating Needs and Features of IBD Experiences (CONFIDE) survey. Methods: Online, quantitative, cross-sectional surveys were conducted separately among HCPs and patients with CD from US and EU5 between May and October 2021. Results: Surveys were completed by 215 US (male [M]=55%, mean age=41 years) and 547 EU5 (M=55%, mean age=38 years) patients. Of these, 58% US and 63% EU5 patients were receiving advanced therapies (biologic/novel oral) and 66% and 63% were receiving steroids at the time of survey completion, respectively. Most patients in the US (61%) and EU5 (62%) reported moderate CD. The top three symptoms currently (past month) experienced by patients were diarrhoea (US: 55%, EU5: 55%), BU (US: 42%, EU5: 38%), and increased stool frequency (US: 40%, EU5: 37%). Among the patients receiving advanced therapies (US: 58%, EU5: 63%), 46% US and 39% EU5 patients experienced BU and 27% US and 19% EU5 patients reported fistula-related symptoms around the anus/rectum. Among patients experiencing BU, only 40% US and 27% EU5 patients were completely comfortable discussing BU with their HCPs and only 27% US and 23% EU5 patients felt comfortable discussing BU-related accidents. Embarrassment was the most common reason for discomfort associated with discussing BU (US: 73%, EU5: 64%) and BU-related accidents (US: 72%, EU5: 66%) with HCPs. A total of 200 US (M=78%) and 503 EU5 (M=71%) HCPs completed the surveys. According to HCPs, the top three patient-reported symptoms were diarrhoea (US: 67%, EU5: 66%), blood in stool (US: 44%, EU5: 24%), and increased stool frequency (US: 32%, EU5: 28%). BU was reported among the top three symptoms only by 19% US and 16% EU5 HCPs. Many HCPs (US: 34%, EU5: 40%) reported not proactively discussing BU, with the most common reason being that they “expect the patient to bring this up if this is an issue” (US: 34%, EU5: 42.0%). Conclusion: Similar to the findings in UC patients, BU was the second most reported symptom among patients with CD, but not among the HCP-perceived top three symptoms. A large proportion of patients with moderate-to-severe CD receiving advanced therapies continued to experience BU. These results indicate a communication gap between HCPs and patients with CD, highlighting the underappreciation of the impacts of BU on patients’ daily lives.

Obesity is recognized by the World Health Organization as a chronic disease. As such, it should be referred to using the language of chronic diseases, with correct and established terminology and definitions. This study was designed to map the current language used to discuss obesity and to compare this with the standard language used for chronic disease. We performed a modified Delphi study to identify the language of chronic disease that is being used in the context of obesity, and to identify discrepancies and potential use of inadequate language with respect to the standard language used for chronic diseases. Participants (n=24) were identified from relevant stakeholder groups and desk research, and included patients, healthcare professionals, policymakers, researchers, industry, and payers (social insurers) of 18 nationalities/regions in Europe, North/South America, and South Africa. Participants were enrolled between 20.10.2020 and 30.10.2020. The study comprised two rounds of qualitative surveys. In Round 1, participants responded to six open-ended questions. Round 2 comprised 38 statements based on key terms/themes identified in Round 1 and covered the definition, causes, progression, treatment, management, and complications of obesity. Consensus was defined as ≥70% participant agreement on a statement. All participants completed Round 1 and 23 participants completed Round 2. In Round 2, consensus was reached for 28 of the 38 statements. Participants reached a consensus regarding the use of statements that acknowledge the heterogeneous nature of obesity, but not on the use of statements that: defined obesity based on body mass index; regarded psychological, physical, or physiological factors among the main causes of obesity; or implied that weight loss should be the aim of obesity treatment. This study uses expert consensus to provide insight into the language used to describe obesity as a chronic disease, and forms the basis for a unified language of obesity. Innovative Medicines Initiative, Novo Nordisk A/S.

The cyclin-dependent kinase (CDK)4/6 inhibitors palbociclib, ribociclib, and abemaciclib are standard-of-care therapy for hormone receptor-positive advanced/metastatic breast cancer, based on randomized trials showing improved progression-free survival for all 3 drugs, and overall survival for ribociclib and abemaciclib. Results in early breast cancer (eBC) are discordant, with sustained improvement in invasive disease-free survival demonstrated for abemaciclib but not other CDK4/6 inhibitors to date. We review non-clinical studies exploring mechanistic differences between the drugs, the impact of continuous dosing on treatment effect, and translational research into potential resistance mechanisms and prognostic and predictive markers. We focus particularly on how emerging findings may help us to understand similarities and differences between the available CDK4/6 inhibitors. Even at late-stage clinical development, there remains much to learn about how agents in this class exert their varying effects.

Question What is the epidemiology and treatment of people with type 2 diabetes (PwT2D) stratified by the presence of cardiovascular disease (CVD) and obesity in Germany?

Background and PurposeSeveral studies have found that the prevalence of migraine is higher among healthcare professionals than in the general population. Furthermore, several investigations have suggested that the personal experiences of neurologists with migraine can influence their perception and treatment of the disease. This study assessed these relationships in Korea.MethodsA survey was used to investigate the following characteristics among neurologists: 1) the prevalence rates of migraine, primary stabbing headache, and cluster headache, and 2) their perceptions of migraine and the pain severity experienced by patients, diagnosing migraine, evaluation and treatment patterns, and satisfaction and difficulties with treatment.ResultsThe survey was completed by 442 actively practicing board-certified Korean neurologists. The self-reported lifetime prevalence rates of migraine, migraine with aura, primary stabbing headache, and cluster headache were 49.8%, 12.7%, 26.7%, and 1.4%, respectively. Few of the neurologists used a headache diary or validated scales with their patients, and approximately half were satisfied with the effectiveness of preventive medications. Significant differences were observed between neurologists who had and had not experienced migraine, regarding certain perceptions of migraine, but no differences were found between these groups in the evaluation and preventive treatment of migraine.ConclusionsThe high self-reported lifetime prevalence rates of migraine and other primary headache disorders among Korean neurologists may indicate that these rates are underreported in the general population, although potential population biases must be considered. From the perspective of neurologists, there is an unmet need for the proper application of headache diaries, validated scales, and effective preventive treatments for patients. While the past experiences of neurologists with migraine might not influence how they evaluate or apply preventive treatments to migraine, they may influence certain perceptions of the disease.