Cost-effectiveness of omalizumab for the treatment of severe pediatric allergic asthma-Results of a real-life study in Spain.

BACKGROUND: Severe pediatric allergic asthma (SPAA) induces a huge economic burden in terms of direct, indirect, and intangible costs. The use of omalizumab for the treatment of these patients has produced a significant improvement in several clinical outcomes, but at the same time, the cost for the management of the disease has also increased. The aim of this report was to evaluate whether the use of omalizumab is cost-effective. METHODS: A sample of 426 children with SPAA from the ANCHORS (Asthma iN CHildren: Omalizumab in Real-life in Spain) study was used to calculate the incremental cost-effectiveness ratio (ICER) for the avoidance of moderate-to-severe exacerbations (MSE) and also for the improvement in childhood Asthma Control Test (c-ACT) or the Asthma Control Questionnaire (ACQ5). We retrospectively collected data on health encounters and drug consumption before and up to 6 years after the beginning of the treatment with omalizumab. RESULTS: The ICER per avoided MSE was €2107 after 1 year, and it consistently decreased to €656 in those followed up to 6 years. Similarly, the ICER for the minimally important difference in control tests showed a decrease from €2059 to €380 per each 0.5 points of improvement in ACQ5 and from €3141 to €2322 per each 3 points improvement in c-ACT, at years 1 and 6, respectively. CONCLUSION: The use of OMZ is a cost-effective option for most children with uncontrolled SPAA, especially those who have frequent exacerbations; the costs are progressively reduced in successive years of treatment.

How bilastine is used to treat allergic rhinitis and urticaria in children.

Management guidelines for allergic rhinitis and urticaria recommend oral second-generation antihistamines as first-line treatment. The efficacy and safety of bilastine, the newest nonsedating second-generation antihistamine, are well established in adolescents/adults with these allergic conditions. The bilastine development program for pediatric use (2-<12 years) followed EMA-authorized processes. Pharmacokinetic/pharmacodynamic simulation and modeling and a pharmacokinetic study were conducted to identify and confirm the pediatric dose (10 mg/day). A Phase III, multicenter, double-blind, randomized, placebo-controlled, parallel-group study was performed to confirm the safety of bilastine 10 mg/day in children. In this article, evidence is reviewed for use of bilastine in children with allergic rhinoconjunctivitis or urticaria. Several cases are presented which demonstrate its role in routine clinical practice.

Omalizumab outcomes for up to 6 years in pediatric patients with severe persistent allergic asthma.

BACKGROUND: Various studies have assessed omalizumab outcomes in the clinical practice setting but follow-up and/or number of patients included were limited. We aim to describe the long-term outcomes of pediatric patients with severe persistent allergic asthma receiving omalizumab in the largest real-life cohort reported to date. METHODS: ANCHORS was a multicenter, observational, retrospective cohort study conducted in 25 Pediatric Allergy and Pulmonology units in Spain. We collected data of patients < 18 years and initiating omalizumab between 2006 and 2018, from the year prior to omalizumab initiation to discontinuation or last available follow-up. The primary outcome was the evolution of the annual number of moderate-to-severe exacerbations compared with the baseline period. RESULTS: Of the 484 patients included, 101 (20.9%) reached 6 years of treatment. The mean ± standard deviation number of exacerbations decreased during the first year of treatment (7.9 ± 6.6 to 1.1 ± 2.0, P < .001) and remained likewise for up to 6 years. The other clinical parameters assessed also improved significantly during the first year and stabilized or continued to improve thereafter. The percentage of patients experiencing adverse events was consistently low, and the main reason for discontinuation was good disease evolution. CONCLUSION: In this large, long-term, observational study, moderate-to-severe exacerbations decreased significantly from the first year of treatment with omalizumab. The beneficial effect was maintained in the long term, along with a good safety profile. Our results position omalizumab as an effective long-term treatment in pediatric patients with severe persistent allergic asthma.

A matter of fat: insulin resistance and oxidative stress.

BACKGROUND: Obesity is linked to insulin resistance (IR), which can lead to type 2 diabetes mellitus. Oxidative stress present in early obesity may favor the progression to comorbid conditions. OBJECTIVE: To examine the relationship between oxidative stress biomarkers and the severity of IR in a group of obese children. METHODS: Forty obese children with a body mass index (BMI) Z-score ≥ 2 were divided into two groups using the median obtained for the homeostasis model assessment of IR (HOMA-IR). Anthropometric parameters (including body fat composition by bioelectrical impedance) and biochemical parameters were assessed. The following biomarkers of oxidative stress were measured: malondialdehyde (MDA), carbonyl groups (CG), reduced glutathione, oxidized low-density lipoprotein, and vitamin E. Comparisons were adjusted for gender and Tanner stage. RESULTS: Children with high values of HOMA-IR were more likely to have high body fat percentage and waist circumferences. However, the BMI Z-score did not correlate to the level of IR. Children with higher values of HOMA-IR presented increased levels of markers of oxidative stress in lipids (MDA, p = 0.005) and proteins (CG, p = 0.015). Moreover, MDA increased with increasing levels of HOMA-IR (r = 0.50, p = 0.002), suggesting that lipoperoxidation increases as IR worsens. In a multivariate regression model, only HOMA-IR was predictive of MDA values, irrespective of adiposity parameters and other metabolic risk factors (r2 = 0.22, p = 0.002). CONCLUSIONS: Oxidative stress increases in obese children according to the severity of IR, which could be linked to the development of comorbidities.

Cystatin C, cardiometabolic risk, and body composition in severely obese children.

The aim of this study was to assess the relationship between cystatin C (CysC), cardiometabolic risk factors (CMRFs), and body composition in severely obese children. We evaluated 117 children aged 7-14 years old. Seventy-nine of these were severely obese (body mass index z-score ranging from 2.1 to 8.4), and 38 were children with normal nutrition state. CysC was determined by immunonephelometry. CMRFs (glucose, insulin, high-density lipoprotein cholesterol, triglycerides, homocysteine, uric acid, alanine aminotransferase, and high-sensitivity C-reactive protein) were measured by standard biochemical methods. Blood pressure was evaluated at the clinical examination. Renal function was estimated using the glomerular filtration rate (eGFR) based upon creatinine levels, and body weight (Léger formula). Body composition was assessed by segmental bioelectrical impedance. Obese children at the highest tertile of CysC values were characterized by their aggregation of CMRFs. CysC concentration was associated with insulin resistance, alanine aminotransferase, uric acid, and homocysteine after adjusting for age, gender, and eGFR. CysC values were also correlated with the fat-free mass and specifically with skeletal muscle mass. CysC levels were correlated with CMRFs factors independently of renal function, and affected by skeletal muscle mass in severely obese children, although they are less influenced by this than is creatinine.