Immune and Metabolic Effects of Antigen-Specific Immunotherapy Using Multiple β-Cell Peptides in Type 1 Diabetes.

Type 1 diabetes is characterized by a loss of tolerance to pancreatic β-cell autoantigens and defects in regulatory T-cell (Treg) function. In preclinical models, immunotherapy with MHC-selective, autoantigenic peptides restores immune tolerance, prevents diabetes, and shows greater potency when multiple peptides are used. To translate this strategy into the clinical setting, we administered a mixture of six HLA-DRB1*0401-selective, β-cell peptides intradermally to patients with recent-onset type 1 diabetes possessing this genotype in a randomized placebo-controlled study at monthly doses of 10, 100, and 500 μg for 24 weeks.

Augmented Expansion of Treg Cells From Healthy and Autoimmune Subjects Adult Progenitor Cell Co-Culture.

Recent clinical experience has demonstrated that adoptive regulatory T (Treg) cell therapy is a safe and feasible strategy to suppress immunopathology induction of host tolerance to allo- and autoantigens. However, clinical trials continue to be compromised due to an inability to manufacture a sufficient Treg cell dose. Multipotent adult progenitor cells (MAPC) promote Treg cell differentiation , suggesting they may be repurposed to enhance expansion of Tregs for adoptive cellular therapy.

Patient preferences for stratified medicine in psoriasis: a discrete choice experiment.

Background: New technologies have enabled the potential for stratified medicine in psoriasis. It is important to understand patients' preferences to enable the informed introduction of stratified medicine, which is likely to involve a number of individual tests that could be collated into a prescribing algorithm for biological drug selection to be used in clinical practice.

Objectives: To quantify patient preferences for an algorithm-based approach to prescribing biologics ('biologic calculator') in psoriasis.

Targeting of antithrombin in hemophilia A or B with investigational siRNA therapeutic fitusiran-Results of the phase 1 inhibitor cohort.

Background: Fitusiran, an investigational small interfering RNA therapy, reduces antithrombin production to rebalance hemostasis in people with hemophilia A or B, with or without inhibitors.

Objectives: To evaluate the safety and efficacy of fitusiran treatment for people with moderate/severe hemophilia A or B with inhibitors.

Patients/methods: In this open-label phase 1, part D study, 17 males with hemophilia A or B with inhibitors received three once-monthly subcutaneous injections of fitusiran 50 mg (n = 6) or 80 mg (n = 11); followed for up to 112 days.

Type 1 diabetes can present before the age of 6 months and is characterised by autoimmunity and rapid loss of beta cells.

Aims/hypothesis: Diabetes diagnosed at <6 months of age is usually monogenic. However, 10-15% of affected infants do not have a pathogenic variant in one of the 26 known neonatal diabetes genes. We characterised infants diagnosed at <6 months of age without a pathogenic variant to assess whether polygenic type 1 diabetes could arise at early ages.

The patient-reported disease burden in adults with atopic dermatitis: a cross-sectional study in Europe and Canada.

Background: Cross-sectional data on patient burden in adults with atopic dermatitis (AD) from real-world clinical practice are limited.

Objective: This study compared patient-reported burden associated with adult AD across severity levels from clinical practices in Canada and Europe.

Methods: This study included adults (18-65 years) diagnosed with AD by dermatologists, general practitioners or allergists.

Persistent C-peptide is associated with reduced hypoglycaemia but not HbA in adults with longstanding Type 1 diabetes: evidence for lack of intensive treatment in UK clinical practice?

Aims: Most people with Type 1 diabetes have low levels of persistent endogenous insulin production. The Diabetes Control and Complications Trial showed that close to diagnosis preserved endogenous insulin was associated with lower HbA , hypoglycaemia and complication rates, when intensively treated. We aimed to assess the clinical impact of persistent C-peptide on rate of hypoglycaemia and HbA in those with long duration (> 5 years) Type 1 diabetes.

Treatment of pustular psoriasis with anakinra: a statistical analysis plan for stage 1 of an adaptive two-staged randomised placebo-controlled trial.

Background: Palmoplantar pustulosis (PPP) is a rare, chronic inflammatory skin disease. It is known to affect quality of life at a level comparable to that from major medical and psychiatric illness, yet current treatment options are remarkably limited. Recent evidence however suggests that interleukin-1 (IL-1) blockade with anakinra will deliver therapeutic benefit in PPP.