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Background: Dupilumab blocks the shared receptor component for interleukin (IL)‐4/IL‐13, key drivers of type 2 inflammation. In phase 2b (NCT01854047) and phase 3 LIBERTY ASTHMA QUEST (NCT02414854), add‐on dupilumab 200/300 mg every 2 weeks (q2w) reduced severe exacerbations, improved prebronchodilator (pre‐BD) forced expiratory volume in 1 second (FEV1) and quality of life measures, and it was generally well tolerated in patients with uncontrolled, persistent (phase 2b), or moderate‐to‐severe (phase 3) asthma. Methods: In patients on high‐dose inhaled corticosteroids (ICS) with type 2‐high asthma (subgroups including baseline blood eosinophils ≥150/300 cells/µL and/or fractional exhaled nitric oxide [FeNO] ≥25 ppb), annualized severe exacerbation rates over the treatment period, changes from baseline in pre‐BD FEV1 and asthma control (5‐item asthma control questionnaire [ACQ‐5]) were analyzed. Results: In high‐dose ICS type 2‐high subgroups, dupilumab 200/300 mg q2w vs placebo in the phase 2b (24 weeks) and phase 3 (52 weeks) studies significantly reduced severe exacerbations by 55%‐69%/57%‐60% (all P<.05) and 53%‐69%/48%‐66% (all P <.001), respectively, except in patients with ≥ 300 eosinophils/µL in phase 2b study (24%/50% (P =.52/0.15). Across subgroups, pre‐BD FEV1 improved by 0.18‐0.22 L/0.19‐0.24 L (all P <.05) and 0.23‐0.36 L/0.15‐0.25 L (all P <.01) and ACQ‐5 scores were reduced by 0.46‐0.55/0.47‐0.85 (all P <.05) and 0.38‐0.50/0.24‐0.30 (all P <.05), respectively, except dupilumab 200 mg q2w in phase 2b in patients with FeNO ≥ 25 ppb (0.41; P =.09). Dupilumab was also effective in patients taking medium‐dose ICS. Conclusion: Dupilumab significantly reduced severe exacerbations and improved lung function and asthma control in patients with type 2‐high asthma on high‐dose ICS at baseline. [ABSTRACT FROM AUTHOR]

Reslizumab 3 mg/kg administered intravenously is approved for the treatment of severe eosinophilic asthma. We assessed the safety and efficacy of subcutaneous reslizumab 110 mg in two trials in patients with uncontrolled severe asthma and increased blood eosinophils. The aim was to establish whether subcutaneous reslizumab 110 mg can reduce exacerbation rates in these patients (study 1) or reduce maintenance oral corticosteroid dose in patients with corticosteroid-dependent asthma (study 2). Both studies were randomised, double-blind, placebo-controlled, phase 3 studies. Entry criteria for study 1 were uncontrolled severe asthma, two or more asthma exacerbations in the previous year, a blood eosinophil count of 300 cells per μL or more (including no more than 30% patients with an eosinophil count <400 cells/μL), and at least a medium dose of inhaled corticosteroids with one or more additional asthma controllers. Patients in study 2 had severe asthma, a blood eosinophil count of 300 cells per μL or more, daily maintenance oral corticosteroid (prednisone 5–40 mg, or equivalent), and high-dose inhaled corticosteroids plus another controller. Patients were randomly assigned (1:1) to subcutaneous reslizumab (110 mg) or placebo once every 4 weeks for 52 weeks in study 1 and 24 weeks in study 2. Patients and investigators were masked to treatment assignment. Primary efficacy outcomes were frequency of exacerbations during 52 weeks in study 1 and categorised percentage reduction in daily oral corticosteroid dose from baseline to weeks 20–24 in study 2. Primary efficacy analyses were by intention to treat, and safety analyses included all patients who received at least one dose of study treatment. These studies are registered with ClinicalTrials.gov , NCT02452190 (study 1) and NCT02501629 (study 2). Between Aug 12, 2015, and Jan 31, 2018, 468 patients in study 1 were randomly assigned to placebo (n=232) or subcutaneous reslizumab (n=236), and 177 in study 2 to placebo (n=89) or subcutaneous reslizumab (n=88). In study 1, we found no significant difference in the exacerbation rate between reslizumab and placebo in the intention-to-treat population (rate ratio 0·79, 95% CI 0·56–1·12; p=0·19). Subcutaneous reslizumab reduced exacerbation frequency compared with placebo in the subgroup of patients with blood eosinophil counts of 400 cells per μL or more (0·64, 95% CI 0·43–0·95). Greater reductions in annual exacerbation risk (p=0·0035) and longer time to first exacerbation were observed for patients with higher trough serum reslizumab concentrations. In study 2, we found no difference between placebo and fixed-dose subcutaneous reslizumab in categorised percentage reduction in daily oral corticosteroid dose (odds ratio for a lower category of oral corticosteroid use in the reslizumab group vs the placebo group, 1·23, 95% CI 0·70–2·16; p=0·47). The frequency of adverse events and serious adverse events with reslizumab were similar to those with placebo in both studies. Fixed-dose (110 mg) subcutaneous reslizumab was not effective in reducing exacerbation frequency in patients with uncontrolled asthma and increased blood eosinophils (≥300 cells/μL), or in reducing the daily maintenance oral corticosteroid dose in patients with oral corticosteroid-dependent severe eosinophilic asthma. Higher exposures than those observed with 110 mg subcutaneous reslizumab are required to achieve maximal efficacy. Teva Branded Pharmaceutical Products R&D. [ABSTRACT FROM AUTHOR]

Background: A post hoc analysis of two randomized, placebo–controlled, Phase 3 trials of intravenous reslizumab, an anti-interleukin-5 (IL-5) biologic for severe eosinophilic asthma. Methods: Relationships between baseline blood eosinophil levels (EOS), forced expiratory volume in 1 s (FEV1) reversibility to β2-agonists and treatment outcomes were assessed. Results: Mean baseline FEV1 reversibility was numerically lower among patients with high (≥ 400 cells/µL) versus low baseline EOS. Reslizumab produced clinically significant improvement in FEV1, exacerbation rates and patient-reported outcomes after 52 weeks, including in patients with high EOS and low FEV1 reversibility (≤ 14%) to β2-agonists at baseline. Conclusions: Clinical trial eligibility criteria stipulating minimum FEV1 reversibility to β2-agonists of ≥ 12% might exclude patients who would benefit from treatment with anti-IL-5 biologics. [ABSTRACT FROM AUTHOR]

Background: Budesonide and formoterol (BF) Spiromax® is a dry powder inhaler designed to deliver BF with maximum ease of use for patients with asthma or chronic obstructive pulmonary disease.Methods: A phase 3b, 12-week, multicenter, double-blind, double-dummy, randomized, controlled trial in patients (≥12 years) with persistent asthma.Primary Objective: to demonstrate non-inferiority of twice-daily BF Spiromax 160/4.5 mcg to BF Turbuhaler® 200/6 mcg in change from baseline in weekly average of daily trough morning peak expiratory flow (PEF). Secondary endpoints included: Patient Satisfaction and Preference Questionnaire scores, change from baseline in evening PEF, trough forced expiratory volume in one second, percentage of symptom-free and rescue-free 24-hour periods, and safety.Results: The analysis was based on the per-protocol population (BF Spiromax, n = 290; BF Turbuhaler, n = 284). The least squares mean change from baseline to week 12 in morning PEF was: BF Spiromax, 18.8 L/min and BF Turbuhaler, 21.8 L/min. Non-inferiority of BF Spiromax vs BF Turbuhaler was demonstrated (the lower limit of the 95% two-sided confidence interval was -9.02 L/min, which is greater than -15 L/min [the criteria specified for non-inferiority]). The mean difference in the total performance domains scores for BF Spiromax vs BF Turbuhaler were 0.248 at baseline and 0.353 at week 12 (both, p <0.001), indicating statistical superiority for BF Spiromax. No statistical or numerical differences were recorded in the total convenience domain score between the two devices. Scores for 'device preference' and 'willingness to continue' supported BF Spiromax at baseline and at week 12 (p = 0.0005 vs BF Turbuhaler). No significant between-group differences were observed in the other secondary efficacy endpoints. Both treatments were well tolerated, with no significant differences in adverse events or asthma exacerbations.Conclusions: This study demonstrates the non-inferiority of BF Spiromax vs BF Turbuhaler in patients (≥12 years) with asthma. More patients preferred the Spiromax device over Turbuhaler for its performance, and were willing to continue therapy with BF Spiromax beyond the 12-week study period.Trial Registration: NCT01803555; February 28, 2013. [ABSTRACT FROM AUTHOR]

Asthma is a chronic inflammatory condition affecting up to 10% of all women of childbearing age. In most patients asthma can be safely treated during pregnancy. However, asthma crises or exacerbations during pregnancy can be life threatening to both the mother and the child. Uncontrolled asthma has been associated with adverse pregnancy outcomes and adverse effects to the fetus (eg, prematurity, low birth weight, increased risk of congenital malformations). Impaired oxygenation during asthma crisis in pregnancy is a major concern. Aggressive treatment of asthma during pregnancy, including the use of systemic corticosteroids if necessary, has been advocated to achieve asthma control and to avoid attacks. Pregnant asthmatics require regular and intensified monitoring. National and international guidelines recommend that antiasthmatic treatment should be maintained and intensified if necessary for the wellbeing of both the mother and the unborn child. Although there is consensus that the potential risks of uncontrolled asthma during pregnancy outweigh the potential risks of antiasthmatic medications the use of the lowest doses possible to achieve andmaintain asthma control is recommended. [ABSTRACT FROM AUTHOR]

Objective. We evaluated montelukast, a leukotriene receptor antagonist (LTRA), added to inhaled corticosteroids (ICS) or ICS+long-acting β2 agonist (LABA) regimens over a period of 1 year to explore the therapeutic effects on asthma patients in patient subgroups. Methods. The majority of patients enrolled in this 12-month, open-label study were ≥18 years of age ( n = 1681) with mild to moderate asthma insufficiently controlled by ICS or ICS+LABA. Patients received montelukast 10 mg qd as add-on therapy and were evaluated at Months 3, 6, 9, and 12. Asthma Control Test (ACT) score in the overall population was the primary endpoint; ACT score categories range from <16 (uncontrolled) to 25 (completely controlled). A post hoc secondary analysis of the following subgroups was conducted. age (< 30 years, 30-50 years, >50 years), gender, presence of allergic rhinitis, duration of asthma (< 5 years, ≥5 years), and the use of ICS or ICS+LABA. Results. Over 12 months of therapy, mean ACT scores improved by 5.7 units ( p < .0001); at baseline, the mean (SD) ACT score for all patients was 14.6 (4.6) and at Month 12, the mean (SD) ACT score was 20.3 (4.2). The subgroups of patients who had allergic rhinitis and those who were <30 years of age demonstrated numerically better ACT scores compared with those who did not have allergic rhinitis or who were >30 years of age. Additional evaluation of the ACT score categories also demonstrated better control among patients who had duration of asthma <5 years and were treated with ICS without LABA. Conclusion. Add-on montelukast demonstrated significant improvement in asthma symptoms over 12 months in all patients in the study. Asthma control was improved in all patient subgroups, but comorbid allergic rhinitis, younger age, shorter duration of asthma, and treatment with only ICS and not ICS+LABA were indicators of better control with add-on montelukast. These observations may likely be shared with other antiasthmatic medications and should be further explored. [ABSTRACT FROM AUTHOR]

Summary: Recommendations in asthma guidelines presuppose that practitioners have the evidence, information, knowledge, and tools to select inhaler devices appropriate for individual patients. Randomised controlled trials usually exclude patients with suboptimal inhaler technique. There is therefore little evidence on which to base inhaler selection in the real world, where patients often use their inhalers incorrectly. The lung deposition of inhaled drug varies according to inhaler device, drug particle size, inhalation technique, and pattern of inspiratory flow. Even with training, not all patients can use their inhalers correctly and maintain inhaler technique; patients may have inability to handle the inhaler, strong negative preferences, or natural breathing patterns that do not match their prescribed inhaler. Therefore, matching device to the patient may be a better course of action than increasing therapy or training and retraining a patient to use a specific inhaler device. Several research questions require answers to meet the goal of helping prescribers make a more informed choice of inhaler type. Is the level of drug deposition in the lungs a key determinant of clinical short- and long-term outcomes? What should be measured by a clinical tool designed to check inhaler technique and therefore help with device selection? If we have a tool to help in individualising inhaler choice, will we achieve better asthma outcomes? Do we have to refine inhaler device choice for each individual, or will we get better outcomes if we select our current best option in light of current knowledge and apply this on a population level? [ABSTRACT FROM AUTHOR]