Long-Term Safety of Dupilumab in Patients With Moderate-to-Severe Asthma: TRAVERSE Continuation Study.

Background: Previous clinical trials have demonstrated dupilumab efficacy and safety in adults and adolescents with moderate to severe asthma for up to 3 years.

Objective: The TRAVERSE continuation study (NCT03620747), a single-arm, open-label study, assessed safety and tolerability of dupilumab 300 mg every 2 weeks up to an additional 144 weeks (∼3 years) in patients with moderate to severe asthma who previously completed TRAVERSE (NCT02134028).

Methods: Primary end points were incidence and event rates per 100 patient-years of treatment-emergent adverse events (TEAEs).

[A municipal health center’s co-constructed therapeutic patient education program for patients with single or multiple morbidities].

Introduction: The accessibility of Therapeutic Patient Education (TPE) is essential to reduce social inequalities and to meet the challenges posed by the increase in chronic diseases. In France, the distribution of TPE throughout the territory is heterogeneous and patients still lack sufficient access. With these perspectives in mind, a municipal health center has developed an innovative TPE device by involving concerned patients from the outset.

Dupilumab improves lung function in patients with uncontrolled, moderate-to-severe asthma.

Background: Dupilumab, a fully human monoclonal antibody, blocks the shared receptor component for interleukin-4 and interleukin-13, key drivers of type 2 inflammation. In the phase 3 LIBERTY ASTHMA QUEST trial (NCT02414854) in patients with uncontrolled, moderate-to-severe asthma, add-on dupilumab 200 mg or 300 mg every 2 weeks reduced exacerbations and improved forced expiratory volume in 1 s (FEV) and quality of life over 52 weeks. This analysis evaluates dupilimab's effect on lung function in the overall population, and subgroups with baseline elevated type 2 inflammatory biomarkers.

Dupilumab Efficacy in Patients with Uncontrolled, Moderate-to-Severe Allergic Asthma.

Background: Dupilumab blocks the shared receptor component for IL-4 and IL-13, key drivers of type 2 inflammation, including IgE-mediated allergic inflammation in asthma. In the LIBERTY ASTHMA QUEST (NCT02414854) study, dupilumab reduced severe asthma exacerbations and improved forced expiratory volume in 1 second (FEV) in patients with uncontrolled, moderate-to-severe asthma with greater efficacy observed in patients with elevated type 2 inflammatory biomarkers (blood eosinophils and fractional exhaled nitric oxide) at baseline.

Objective: We assessed dupilumab's effect on key asthma outcomes in QUEST patients with/without evidence of allergic asthma (total serum IgE ≥30 IU/mL and ≥1 perennial aeroallergen-specific IgE ≥0.

Cost burden and resource utilization in patients with chronic rhinosinusitis and nasal polyps.

Objectives/hypothesis: Establish treatment patterns and economic burden in US patients with chronic rhinosinusitis with nasal polyposis (CRSwNP) versus without chronic rhinosinusitis (CRS). Determine comparative costs of subgroups with high clinical burden.

Study Design: Observational, retrospective, case-control study.

Efficacy and safety of dupilumab in perennial allergic rhinitis and comorbid asthma.

Background: Dupilumab, an anti-IL-4 receptor α mAb, inhibits IL-4/IL-13 signaling, key drivers of type 2/T2 immune diseases (eg, atopic/allergic disease). In a pivotal, phase 2b study (NCT01854047), dupilumab reduced severe exacerbations, improved lung function and quality of life, and was generally well tolerated in patients with uncontrolled persistent asthma despite using medium-to-high-dose inhaled corticosteroids plus long-acting β2-agonists.

Objective: To examine dupilumab's effect on the 22-item Sino-Nasal Outcome Test (SNOT-22) total score and its allergic rhinitis (AR)-associated items in asthma patients with comorbid perennial allergic rhinitis (PAR).

Design and rationale of the ODYSSEY DM-DYSLIPIDEMIA trial: lipid-lowering efficacy and safety of alirocumab in individuals with type 2 diabetes and mixed dyslipidaemia at high cardiovascular risk.

Background: Type 2 diabetes mellitus (T2DM) is often associated with mixed dyslipidaemia, where non-high-density lipoprotein cholesterol (non-HDL-C) levels may more closely align with cardiovascular risk than low-density lipoprotein cholesterol (LDL-C). We describe the design and rationale of the ODYSSEY DM-DYSLIPIDEMIA study that assesses the efficacy and safety of alirocumab, a proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitor, versus lipid-lowering usual care in individuals with T2DM and mixed dyslipidaemia at high cardiovascular risk with non-HDL-C inadequately controlled despite maximally tolerated statin therapy. For the first time, atherogenic cholesterol-lowering with a PCSK9 inhibitor will be assessed with non-HDL-C as the primary endpoint with usual care as the comparator.

Efficacy and safety of alirocumab in insulin-treated patients with type 1 or type 2 diabetes and high cardiovascular risk: Rationale and design of the ODYSSEY DM-INSULIN trial.

Aims: The coadministration of alirocumab, a PCSK9 inhibitor for treatment of hypercholesterolaemia, and insulin in diabetes mellitus (DM) requires further study. Described here is the rationale behind a phase-IIIb study designed to characterize the efficacy and safety of alirocumab in insulin-treated patients with type 1 (T1) or type 2 (T2) DM with hypercholesterolaemia and high cardiovascular (CV) risk.

Methods: ODYSSEY DM-INSULIN (NCT02585778) is a randomized, double-blind, placebo-controlled, multicentre study that planned to enrol around 400 T2 and up to 100 T1 insulin-treated DM patients.

Effect of alirocumab dose increase on LDL lowering and lipid goal attainment in patients with dyslipidemia.

Objectives: The objective of this study is to report the dose response in ODYSSEY phase 3 clinical trials of proprotein convertase subtilisin kexin type 9 inhibition with alirocumab in patients not at prespecified lipid goals who received a per-protocol dose increase from 75 every 2 weeks (Q2W) to 150 mg Q2W.

Methods: Patients (n=2181) receiving statins were enrolled in six phase 3 randomized, double-blind, double-dummy trials (24-104 weeks): alirocumab versus placebo or ezetimibe 10 mg/day. The 75 mg subcutaneous Q2W dose was increased to 150 mg at week 12 if week 8 LDL cholesterol (LDL-C) was greater than or equal to 70 mg/dl (>100 mg/dl in OPTIONS studies for patients without previous coronary heart disease, but with other risk factors).

HDL cholesterol, very low levels of LDL cholesterol, and cardiovascular events.

Background: High-density lipoprotein (HDL) cholesterol levels are a strong inverse predictor of cardiovascular events. However, it is not clear whether this association is maintained at very low levels of low-density lipoprotein (LDL) cholesterol.

Methods: A post hoc analysis of the recently completed Treating to New Targets (TNT) study assessed the predictive value of HDL cholesterol levels in 9770 patients.

[Operative risk of heart valve surgery after 80 years].

The continuous prolongation of life expectancy in developed nations and the progress made in the surgical treatment of valvulopathy have substantially increased the number of octogenarians undergoing heart valve surgery with extracorporeal circulation. Most of them have calcified aortic stenosis and the valve is replaced with a bioprosthesis. At these ages, mitral valve disease--usually insufficiency--is predominantly treated by repair rather than valve replacement.

Questions for COPD diagnostic screening in a primary care setting.

Objectives: To test questions usable in an ambulatory clinic to identify persons likely to have chronic obstructive pulmonary disease (COPD).

Methods: Analyses were performed as part of a study to identify patients with likely COPD in the Glenfield UK primary care clinic. Patients age 40 and older were recruited based on one of the following criteria: (1) respiratory medications in previous 2 years; (2) history of smoking or (3) history of asthma with no current medications based on case notes.

Comparison of existing symptom-based questionnaires for identifying COPD in the general practice setting.

Objective: Underdiagnosis of COPD is widespread, at least in part due to underuse of spirometry. Symptom-based questionnaires may be helpful as an adjunct to spirometry. The aim of this study was to determine which types of questions might aid in identifying COPD.

Single-pill therapy in the treatment of concomitant hypertension and dyslipidemia (the amlodipine/atorvastatin gemini study).

The Gemini Study was a 14-week, open-label, non-comparative, office-based, multicenter trial to evaluate single-pill therapy in the treatment of concomitant hypertension and dyslipidemia. In addition to recommending lifestyle modifications, eight dosage strengths of amlodipine/atorvastatin single pill (5/10, 5/20, 5/40, 5/80, 10/10, 10/20, 10/40, and 10/80 mg) were electively titrated to improve blood pressure and lipid control. A total of 1220 patients with uncontrolled hypertension at baseline received study medication.

[Can bioprostheses be implanted at younger ages?].

The choice between mechanical prosthesis (MP) and bioprosthesis (BP) depends on the respective advantages and disadvantages of the two types of valves. MP theoretically have an indefinite life span but carry the risk of thromboembolic events that requires anticoagulant therapy, which itself is responsible for hemorrhages. BP bear a theoretically lower thromboembolic risk but have a limited life span that requires reintervention at a subsequent date, latter when the patient is older at implantation and operated on for aortic replacement.

[Anticoagulation of valvular prostheses].

Prosthetic valve replacement has transformed the outcome of patients with severe or poorly tolerated valvular heart disease. Between the two main families of prostheses, only mechanical prostheses require indefinite anticoagulant therapy to lower the thromboembolic risk. National and international guidelines have been published within the past decade.

[The best of valvular heart disease in 2002].

For AS, besides a very thorough update by Carabello on their management, new experimental work confirms that the pathophysiology of the condition is closer to atherosclerotic and inflammatory processes than pure degeneration. Moreover this year brings a batch of long term post-operative results, one of which is an important series relating to 2194 bioprostheses followed up for 15 years. The choice of valvular substitute between 60 and 70 years old is the subject for several studies.

[Aortic stenosis with left ventricular dysfunction: evaluation and management].

Aortic stenosis is the most frequent valvulopathy in France today. Valve replacement has transformed the prognosis, when indications are present before the appearance of irreversible left ventricular dysfunction. However, some patients are still not seen before this time or their surgery was deferred.

[The best of 2001. Valve diseases].

The publications in 2001 regarding valvulopathies have concerned all sectors of this pathology. Aortic valvulopathies are the object of new work supporting the relationship between aortic sclerosis or stenosis and cardiovascular risk factors. They confirm the analogy between lesions of inflammatory origin observed on calcified valves and atherosclerotic plaques (Mohlner).

Analysis of risk factors for local delivery of low- and intermediate-dose adenovirus gene transfer vectors to individuals with a spectrum of comorbid conditions.

In this study we analyze the adverse events and abnormal laboratory parameters following local administration of low (<10(9) particle units) and intermediate (10(9)-10(11) particle units) single and repetitive doses (140 total) of E1(-)E3(-) adenovirus (Ad) gene transfer vectors administered to the respiratory epithelium, solid tumors, skin, myocardium, and skeletal muscle in eight gene transfer trials since April 1993. In the accompanying paper by Harvey et al., (Hum.

Safety of local delivery of low- and intermediate-dose adenovirus gene transfer vectors to individuals with a spectrum of morbid conditions.

To help define the safety profile of the use of adenovirus (Ad) gene transfer vectors in humans, this report summarizes our experience since April 1993 of the local administration of E1(-)/E3(-) Ad vectors to humans using low (<10(9) particle units) or intermediate (10(9)-10(11) particle units) doses. Included in the study are 90 individuals and 12 controls, with diverse comorbid conditions, including cystic fibrosis, colon cancer metastatic to liver, severe coronary artery disease, and peripheral vascular disease, as well as normals. These individuals received 140 different administrations of vector, with up to seven administrations to a single individual.

[The best in 2000 on valve diseases].

During the year 2000, publications on valvular heart disease have concerned all aspects of this field of cardiology at a time when old and dated therapeutic procedures are being reassessed. The ageing population of the developed world has led to aortic stenosis playing a large part, and the study of its natural history has provided two keynote publications. Aortic valve replacement, increasingly involving older patients, led to the evaluation of this surgery in this age group in which bioprostheses are often associated with coronary bypass surgery.