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 (FEV1) 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. Methods: Patients were randomised to 52 weeks of subcutaneous dupilumab 200 mg every 2 weeks, 300 mg every 2 weeks, or matched-volume placebos. Lung function outcomes were analysed in the overall population, in patients with ≥150 eosinophils·µL−1, ≥300 eosinophils·µL−1, ≥25 ppb fractional exhaled nitric oxide (FeNO), and both ≥150 eosinophils·µL−1 and ≥25 ppb FeNO, at baseline. Results: Dupilumab treatment (200 mg and 300 mg every 2 weeks) resulted in significant improvements versus placebo after 52 weeks in pre-bronchodilator FEV1 (0.20 and 0.13 L, respectively, versus placebo) and post-bronchodilator FEV1 (0.19 and 0.13 L, respectively), forced vital capacity (FVC) (0.20 and 0.14 L, respectively), forced expiratory flow (0.19 and 0.13 L·s−1, respectively) and pre-bronchodilator FEV1/FVC ratio (1.75% and 1.61%, respectively) in the overall population (p<0.001). Difference versus placebo in post-bronchodilator FEV1 slope of change (weeks 4–52) was significant (0.04 L·year−1; p<0.05). Greater improvements were achieved in patients with elevated baseline blood eosinophil and/or FeNO levels for most outcomes. Conclusions: Dupilumab improves lung function outcomes, including large and small airway measurements and fixed airway obstruction, in patients with uncontrolled, moderate-to-severe asthma; particularly in patients with elevated biomarkers of type 2 inflammation

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). LDL-C percentage reductions from baseline (on-treatment data, n=1291) were compared at week 12 versus week 24. Results: Most patients (n=951; 73.7%) with 75 mg Q2W dose plus background statin achieved LDL-C less than 70 or less than 100 mg/dl at week 8. In 340 (26.3%) patients, alirocumab dose was increased to 150 mg Q2W at week 12, and 60.9% of these patients achieved LDL-C goals at week 24, with an additional 14.2% reduction in LDL-C from week 12 to week 24. Adverse event rates were comparable in patients with versus without a dose increase (72.4 vs. 71.8% in placebo-controlled trials; 67.0 vs. 67.6% in ezetimibe-controlled trials). Conclusion: Most patients achieved LDL-C goals with alirocumab 75 mg Q2W plus statins. Of those (26.3%) receiving a dose increase, 60.9% achieved LDL-C goals at week 24 with an additional 14.2% reduction in LDL-C

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 150mg 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 150mg 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). LDL-C percentage reductions from baseline (on-treatment data, n=1291) were compared at week 12 versus week 24. Results Most patients (n=951; 73.7%) with 75 mg Q2W dose plus background statin achieved LDL-C less than 70 or less than 100 mg/dl at week 8. In 340 (26.3%) patients, alirocumab dose was increased to 150 mg Q2W at week 12, and 60.9% of these patients achieved LDL-C goals at week 24, with an additional 14.2% reduction in LDL-C from week 12 to week 24. Adverse event rates were comparable in patients with versus without a dose increase (72.4 vs. 71.8% in placebo-controlled trials; 67.0 vs. 67.6% in ezetimibe-controlled trials). Conclusion Most patients achieved LDL-C goals with alirocumab 75 mg Q2W plus statins. Of those (26.3%) receiving a dose increase, 60.9% achieved LDL-C goals at week 24 with an additional 14.2% reduction in LDL-C. Copyright (C) 2017 The Author(s). Published by Wolters Kluwer Health, In

Dupilumab improves mental health measures in patients with chronic rhinosinusitis and nasal polyposis (CRSwNP)

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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. The primary outcome measure was the time to a first major cardiovascular event, defined as death from coronary heart disease, nonfatal non-procedure-related myocardial infarction, resuscitation after cardiac arrest, or fatal or nonfatal stroke. The predictive relationship between HDL cholesterol levels at the third month of treatment with statins and the time to the first major cardiovascular event was assessed in univariate and multivariate analyses and was also assessed for specific LDL cholesterol strata, including subjects with LDL cholesterol levels below 70 mg per deciliter (1.8 mmol per liter). RESULTS: The HDL cholesterol level in patients receiving statins was predictive of major cardiovascular events across the TNT study cohort, both when HDL cholesterol was considered as a continuous variable and when subjects were stratified according to quintiles of HDL cholesterol level. When the analysis was stratified according to LDL cholesterol level in patients receiving statins, the relationship between HDL cholesterol level and major cardiovascular events was of borderline significance (P=0.05). Even among study subjects with LDL cholesterol levels below 70 mg per deciliter, those in the highest quintile of HDL cholesterol level were at less risk for major cardiovascular events than those in the lowest quintile (P=0.03). CONCLUSIONS: In this post hoc analysis, HDL cholesterol levels were predictive of major cardiovascular events in patients treated with statins. This relationship was also observed among patients with LDL cholesterol levels below 70 mg per deciliter. (ClinicalTrials.gov number, NCT00327691 [ClinicalTrials.gov].

Lasten fyysinen aktiivisuus : Lapin ja Pohjois-Pohjanmaan 3.- ja 5.-luokkalaiset

Opinnäytetyömme tavoitteena oli saada tietoa Lapin ja Pohjois-Pohjanmaan 3.- ja 5.-luokkalaisten fyysisestä aktiivisuudesta. Työmme tarkoituksena oli selvittää, liikkuvatko lapset liikuntasuositusten mukaisesti ja näin ollen terveytensä kannalta riittävästi. Lisäksi selvitimme, kuinka paljon ja millä intensiteetillä lapset liikkuivat, sekä kuinka paljon he viettivät aikaa istuen ja makuulla valveillaoloajastaan. Työmme tulokset antavat aluekohtaista tietoa, jota voidaan hyödyntää tutkimusalueiden lasten liikkumisen kehittämisessä. Työmme oli määrällinen tutkimus, jossa tutkimustietoa kerättiin objektiivisesti liikemittareiden avulla. Liikemittarilla kerättiin tietoa lasten päivittäisestä liikkumisesta vähintään neljän päivän ajalta. Työmme aineisto pohjautuu LIITU 2016 - tutkimuksen aineistoon. Tutkimus toteutettiin keväällä 2016, ja tutkimuksemme otos koostui 394 alakouluikäisestä lapsesta. Teimme tutkimuksen yhteistyössä UKK-instituutin kanssa, ja saimme liikemittareista saadut datatiedot heiltä. Analysoimme liikemittareiden datatiedot keskimääräisten osuuksien perusteella. Tutkimustuloksemme osoittivat, että lasten liikkuminen ja paikallaanolo muuttuivat iän myötä. Sukupuolten välillä havaittiin myös eroja. Lapset viettivät noin puolet valveillaoloajastaan istuen ja makuuasennossa. Nuoremman ikäluokan lapset olivat aktiivisempia päivän aikana kuin vanhemman ikäluokan lapset. Paikallaan oloa kertyi 3.-luokkaisille vähemmän kuin 5.-luokkalaisille. Pojat viettivät enemmän aikaa paikallaan kuin tytöt, mutta myös liikkuivat reippaasti ja rasittavasti heitä enemmän. Noin puolet lapsista liikkui terveytensä kannalta riittävästi. Liikuntasuositusten toteutumisessa oli suuria eroja ikäryhmien ja sukupuolten välillä. Lasten tulisi liikkua reippaasti ja rasittavasti läpi elämän, ja heidän tulisi täyttää liikuntasuositukset. Tämä pohjautuu reippaan ja rasittavan liikkumisen terveyshyötyihin. Lasten terveydelle on parasta liikkua reippaasti päivittäin ja välttää paikallaanoloa. Passiivisuudella on todettu olevan terveydelle haitallisia tekijöitä.The aim of our thesis was to gather information about 3rd and 5th graders’ physical activity in Lapland and North Ostrobothnia. Our purpose was to study whether children exercise conforming to the physical activity guidelines as to maintain good health. In addition, we researched on how much and with what level of intensity these children moved and how much time they spent sitting and laying down while being awake. The results of our thesis provide information about regional activity habits that can be used in development of children's’ physical activity in those regions. Our thesis was a quantitative study in which the objective research data was collected by using accelerometers. The statistics of children’s daily activities were gathered with the accelerometers during four days. Our study is based on the LIITU 2016 -study. The study was conducted in collaboration with UKK institute in the spring of 2016 and 394 primary schoolers took part in it. After they gave us the data of accelerometers, we analysed results using the mediocre method. Our results indicated that the amount of activity and sedentary behaviour in children changes with age. There were also noticeable differences between genders. Children spent approximately half of their time awake in a sitting position or laying down. The children in the younger age group were less sedentary and they did more physical activities during the day than the children in the older age group. Boys spent more time being sedentary compared to girls but they also did more moderate- and vigorous-intensity activities than girls. About half of the children fulfilled the recommendations of the physical activity guidelines. There were multiple differences in the fulfilment of the physical activity guidelines between ages and genders. The children should fulfil the recommendations of physical activity. The recommendations are based on the positive health effects of moderate- and vigorous-intensity moving. Sedentary behaviour has many negative effects to health and children should reduce being sedentary

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. Methods This study matched patients with CRSwNP to patients without CRS (1:1) using the Truven Health MarketScan US claims database. Categorical and continuous variables were compared using McNemar test and paired t test (normal distribution) or Wilcoxon signed rank tests (non-normal distribution). Within subgroups, chi(2) and Wilcoxon or t tests were used (normal distribution). Results There were 10,841 patients with CRSwNP and 10,841 patients without CRS included. Mean age in the CRSwNP cohort was 45.8 years; 56.2% were male. During follow-up, patients with CRSwNP had an increased diagnosis of asthma versus patients without CRS (20.8% vs. 8.1%, respectively; P < .001). Annual incremental costs were $11,507 higher for patients with CRSwNP versus those without CRS. Costs were higher in subgroups of patients with CRSwNP undergoing functional endoscopy sinus surgery (FESS), with a comorbid diagnosis of asthma, receiving oral corticosteroids, or macrolides versus the overall CRSwNP group. Patients with CRSwNP undergoing FESS had the highest costs of the four subgroups ($26,724, $22,456,$20,695, and $20,990, respectively). Conclusions Annual incremental costs were higher among patients with CRSwNP versus without CRS. Patients with CRSwNP with high clinical burden had higher overall costs than CRSwNP patients without. Level of Evidence NA Laryngoscope, 129:1969-1975, 201

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. Methods This study matched patients with CRSwNP to patients without CRS (1:1) using the Truven Health MarketScan US claims database. Categorical and continuous variables were compared using McNemar test and paired t test (normal distribution) or Wilcoxon signed rank tests (non-normal distribution). Within subgroups, chi(2) and Wilcoxon or t tests were used (normal distribution). Results There were 10,841 patients with CRSwNP and 10,841 patients without CRS included. Mean age in the CRSwNP cohort was 45.8 years; 56.2% were male. During follow-up, patients with CRSwNP had an increased diagnosis of asthma versus patients without CRS (20.8% vs. 8.1%, respectively; P < .001). Annual incremental costs were $11,507 higher for patients with CRSwNP versus those without CRS. Costs were higher in subgroups of patients with CRSwNP undergoing functional endoscopy sinus surgery (FESS), with a comorbid diagnosis of asthma, receiving oral corticosteroids, or macrolides versus the overall CRSwNP group. Patients with CRSwNP undergoing FESS had the highest costs of the four subgroups ($26,724, $22,456,$20,695, and $20,990, respectively). Conclusions Annual incremental costs were higher among patients with CRSwNP versus without CRS. Patients with CRSwNP with high clinical burden had higher overall costs than CRSwNP patients without. Level of Evidence NA Laryngoscope, 129:1969-1975, 201

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

Altres ajuts: Sanofi and Regeneron Pharmaceuticals, Inc (NCT02134028 and NCT03620747)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). Secondary end points included adverse events (AEs) of special interest, serious AEs, and AEs leading to study discontinuation. Results: A total of 393 patients participated in the TRAVERSE continuation study (cumulative dupilumab exposure, 431.7 patient-years; median treatment duration, 309 days). A total of 29 patients (7.4%) received more than 958 days of treatment. A total of 214 (54.5%) patients reported at least 1 TEAE (event rate: 171.4); 37 (9.4%) experienced at least 1 treatment-related TEAE, none of which were considered severe; 2 patients reported 6 TEAEs of moderate intensity. A total of 22 (5.6%) patients reported serious AEs (event rate: 6.9). AEs of special interest were reported in 24 patients (6.1%; event rate: 6.0). Five (1.3%) deaths occurred (event rate: 1.2) following serious AEs of coronavirus disease 2019 (COVID-19)-related pneumonia (3 patients), pancreatitis (1 patient), and pulmonary embolism (1 patient). None of the TEAEs leading to death were considered treatment-related. Conclusions: Dupilumab treatment was well tolerated for up to an additional 3 years. Safety findings were consistent with the known safety profile of dupilumab. These findings further support the long-term use of dupilumab in patients with moderate to severe asthma