Treatment with glucagon-like peptide-1 receptor agonists and incidence of dementia:Data from pooled double-blind randomized controlled trials and nationwide disease and prescription registers

INTRODUCTION: People with type 2 diabetes have increased risk of dementia. Glucagon‐like peptide‐1 (GLP‐1) receptor agonists (RAs) are among the promising therapies for repurposing as a treatment for Alzheimer's disease; a key unanswered question is whether they reduce dementia incidence in people with type 2 diabetes. METHODS: We assessed exposure to GLP‐1 RAs in patients with type 2 diabetes and subsequent diagnosis of dementia in two large data sources with long‐term follow‐up: pooled data from three randomized double‐blind placebo‐controlled cardiovascular outcome trials (15,820 patients) and a nationwide Danish registry‐based cohort (120,054 patients). RESULTS: Dementia rate was lower both in patients randomized to GLP‐1 RAs versus placebo (hazard ratio [HR]: 0.47 (95% confidence interval [CI]: 0.25–0.86) and in the nationwide cohort (HR: 0.89; 95% CI: 0.86–0.93 with yearly increased exposure to GLP‐1 RAs). DISCUSSION: Treatment with GLP‐1 RAs may provide a new opportunity to reduce the incidence of dementia in patients with type 2 diabetes

Limited value of routine follow-up visits in chronic lymphocytic leukemia managed initially by watch and wait:A North Denmark population-based study

IntroductionThe majority of newly diagnosed chronic lymphocytic leukemia (CLL) patients are followed initially by watch and wait (WAW). Clinical practice varies and the value of frequent follow-up visits remains unclear. Thus, in this study we investigated the clinical value of follow-up visits for patients with CLL.MethodsWe collected data from diagnosis and follow-up visits for patients diagnosed with CLL and managed by WAW in the North Denmark Region between 2007–2014. High- and low-risk group patients were determined by Binet stage, IgVH status, and cytogenetics at diagnosis. The effect of risk group allocation on the probability of receiving CLL-directed treatment within two years was included in a multivariable logistic regression model adjusted for age and blood test results.Results273 patients were included in the study with a median follow-up of 3 years (IQR: 1.6–5.4). Overall, the median interval between follow-up visits was 98 days (95% CI: 96–100) (high-risk patients: 91 days [95% CI: 86–95] vs. low-risk patients: 105 days [95% CI: 100–110]). Among 2,312 follow-up visits, only 387 (17%) were associated with interventions. At the following time points: 6 months, 1 year, and 1.5 years, patients with low-risk CLL had significantly lower odds of initiating treatment compared to patients with high-risk CLL.ConclusionWAW plays an important role in managing CLL. Interventions at follow-up visits were infrequent and low-risk patients had significantly lower risk of treatment initiation. We question the value of routine follow-up in CLL in the absence of changes in symptoms and/or blood test results.</div

Subtype assignment of CLL based on B-cell subset associated gene signatures from normal bone marrow – A proof of concept study

Diagnostic and prognostic evaluation of chronic lymphocytic leukemia (CLL) involves blood cell counts, immunophenotyping, IgVH mutation status, and cytogenetic analyses. We generated B-cell associated gene-signatures (BAGS) based on six naturally occurring B-cell subsets within normal bone marrow. Our hypothesis is that by segregating CLL according to BAGS, we can identify subtypes with prognostic implications in support of pathogenetic value of BAGS. Microarray-based gene-expression samples from eight independent CLL cohorts (1,024 untreated patients) were BAGS-stratified into pre-BI, pre-BII, immature, naïve, memory, or plasma cell subtypes; the majority falling within the memory (24.5–45.8%) or naïve (14.5–32.3%) categories. For a subset of CLL patients (n = 296), time to treatment (TTT) was shorter amongst early differentiation subtypes (pre-BI/pre-BII/immature) compared to late subtypes (memory/plasma cell, HR: 0.53 [0.35–0.78]). Particularly, pre-BII subtype patients had the shortest TTT among all subtypes. Correlates derived for BAGS subtype and IgVH mutation (n = 405) revealed an elevated mutation frequency in late vs. early subtypes (71% vs. 45%, P < .001). Predictions for BAGS subtype resistance towards rituximab and cyclophosphamide varied for rituximab, whereas all subtypes were sensitive to cyclophosphamide. This study supports our hypothesis that BAGS-subtyping may be of tangible prognostic and pathogenetic value for CLL patients