A review of the value of innovation in inhalers for COPD and asthma

Background: Appropriate use of inhaled therapies for asthma and chronic obstructive pulmonary disease (COPD) is critical to ensuring good patient outcomes, efficient use of healthcare resources and limiting the effects of high-morbidity. The appropriate choice of inhaler and active therapy, incorporating patient preferences, can help improve treatment adherence and long-term outcomes. Despite this, many current inhalers are non-intuitive to use, and require extensive training. Methods: In this review, an expert panel considers the evidence for the use of inhaler devices in management of COPD and asthma. The panel also evaluates the value of innovation in inhaler technologies, which optimise the use of existing molecules from a clinical, economic and societal perspective. Conclusions: The panel conclusion is that there remains a substantial unmet need in inhaler technology and that innovation in inhaler devices can provide real-world health benefits to patients. Furthermore, we recommend that these innovations should be supported by healthcare systems through appropriate pricing and reimbursement mechanisms. Keywords: Asthma; Chronic obstructive pulmonary disease; innovation; patient preference; adherence; patient compliance; metered dose inhaler; dry powder inhaler; medication errors; valu

Extrafine triple therapy in patients with asthma and persistent airflow limitation

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Advancing precision medicine in asthma: Evolution of treatment outcomes

: The article discusses the historical evolution of asthma treatment and highlights recent advancements in personalized medicine, specifically the use of biologics in severe asthma therapy and its potential combination with allergen immunotherapy (AIT). One of the major breakthroughs of biologics is their potential effect on airway remodeling, a crucial aspect of asthma chronicity. The article introduces the concept of disease-modifying antiasthmatic drugs, which aim to modify the course of asthma and possibly modulate or prevent airway remodeling. Furthermore, the critical importance of patient-centered outcome measures to evaluate the efficacy and effectiveness of asthma treatments is emphasized, with the innovative concept of asthma remission introduced as a potential outcome. Recent studies suggest that AIT can be used as an additional therapy to biologic agents for the treatment of allergic asthma. The combination of these treatments has been shown to induce improved clinical outcomes. However, AIT is actually not recommended for use in patients with severe asthma, but encouraging results from studies investigating the combined use of AIT and biologics indicate a novel approach to exploring these treatment modalities. In conclusion, the introduction of biologics and AIT has changed the scenario of respiratory allergy treatment, from a "one size fits all" approach to embracing "individual treatments.

Efficacy and safety of SQ house dust mite (HDM) SLIT-tablet treatment of HDM allergic asthma

ABSTRACT: Introduction: In the treatment of house dust mite (HDM) respiratory allergic disease, allergy immunotherapy constitutes an add-on treatment option targeting the underlying immunological mechanisms of allergic disease. However, for the treatment of HDM allergic asthma, the use of subcutaneous allergy immunotherapy (SCIT) has been limited by the risk of systemic adverse events. Thus, sublingually administered allergy immunotherapy (SLIT) has been investigated as a treatment option with an improved tolerability profile that allows for safer treatment of patients with HDM allergic asthma. Areas covered: In this Drug Profile, we provide a review of the clinical data behind the SQ HDM SLIT-tablet, which was recently approved for the treatment of HDM allergic asthma and allergic rhinitis by regulatory authorities in several European countries. Expert commentary: The SQ HDM SLIT-tablet is the first allergy immunotherapy to be tested prospectively in patients with asthma, and to favorably modify patient relevant end points such as requirement for inhaled corticosteroid (ICS) or the time to first asthma exacerbation upon ICS reduction, suggesting that SQ HDM SLIT-tablet treatment may contribute to improving overall asthma control

Extrafine triple therapy and asthma exacerbation seasonality: TRIMARAN and TRIGGER post-hoc analyses

Background: Previous studies have shown seasonal variation in asthma exacerbations, peaking over the winter months. A single-inhaler triple therapy containing extrafine formulations of the inhaled corticosteroid (ICS) beclomethasone dipropionate (BDP), long-acting β2-agonist (LABA) formoterol fumarate (FF) and long-acting muscarinic antagonist (LAMA) glycopyrronium (G) is in development for asthma. Objective: To evaluate whether calendar season impacted the relative effect of BDP/FF/G versus BDP/FF on moderate-and-severe asthma exacerbations. Methods: TRIMARAN and TRIGGER were double-blind 52-week studies comparing BDP/FF/G with BDP/FF (TRIMARAN medium-dose ICS; TRIGGER high-dose) in adults with uncontrolled asthma (Asthma Control Questionnaire-7 ≥1.5), pre-bronchodilator FEV1 <80% predicted, history of ≥1 asthma exacerbation, who had been receiving ICS/LABA for ≥4 weeks prior to entry. Moderate and severe asthma exacerbations were captured throughout each study. In these post-hoc analyses, the annual moderate-and-severe exacerbation rate was calculated for each month, with rate ratios determined from events grouped by season. Results: In patients who received BDP/FF alone, there was a marked seasonal effect on the occurrence of asthma exacerbations, with the rate highest in the winter months. However, the addition of the LAMA component to BDP/FF reduced this seasonal variation, especially during the winter, such that the relative effect of BDP/FF/G versus BDP/FF was greatest in the winter (significant 20.3% reduction [p=0.0008]). Reductions in the other seasons ranged between 8.6 and 12.0%. Conclusions: These post-hoc analyses indicate that inhaled triple therapy with extrafine BDP/FF/G reduces seasonal peaks in moderate-and-severe exacerbations, and confirm the overall utility of adding LAMA to ICS/LABA in the management of asthma

Determinants of response to inhaled extrafine triple therapy in asthma: analyses of TRIMARAN and TRIGGER

Background: A number of single-inhaler triple therapies are being developed for asthma, including the extrafine formulation of beclometasone dipropionate (BDP), formoterol fumarate (FF), and glycopyrronium (G). Given asthma is a heterogenous disease, we investigated whether the clinical response to the addition of the long-acting muscarinic antagonist component within inhaled triple therapy was impacted by a range of clinical characteristics.Methods: These were pre-specified and post-hoc sub-group analyses of TRIMARAN and TRIGGER, which were double-blind, 52-week studies comparing medium-strength (100/6/10 µg; TRIMARAN) and high-strength (200/6/10 µg; TRIGGER) BDP/FF/G with the respective BDP/FF strengths in adults with uncontrolled asthma and a history of ≥ 1 exacerbation. Co-primary endpoints were pre-dose forced expiratory volume in 1 s (FEV1) at Week 26 and the rate of moderate-to-severe exacerbations over 52 weeks. Key secondary endpoints: peak FEV1 at Week 26 and average morning peak expiratory flow over the first 26 weeks in each study, and severe exacerbation rate over 52 weeks (pooled data).Results: Baseline clinical characteristics (pre-specified analyses) had no consistent effect on the lung function improvements with BDP/FF/G. For the exacerbation endpoints, sub-groups with higher reversibility gained greatest relative benefit from BDP/FF/G versus BDP/FF. In post-hoc analyses with patients sub-grouped by screening blood eosinophil values, in TRIMARAN the greatest relative effect of BDP/FF/G versus BDP/FF on the lung function endpoints was in the ≤ 300 cells/µL group; in TRIGGER, eosinophil levels did not markedly influence the relative efficacy of BDP/FF/G versus BDP/FF. Eosinophil levels did not influence relative efficacy on moderate-to-severe or severe exacerbations.Conclusion: Overall, the relative efficacy of extrafine BDP/FF/G versus BDP/FF was not influenced by a range of clinical characteristics. However, some patient sub-groups gained additional benefit from BDP/FF/G for certain endpoints. In particular, for exacerbations the relative efficacy of BDP/FF/G was greater in more reversible patients.Trial registration ClinicalTrials.gov: TRIMARAN, NCT02676076 (registered February 8, 2016, https://clinicaltrials.gov/ct2/show/NCT02676076?term=NCT02676076&draw=2&rank=1,); TRIGGER, NCT02676089 (registered February 8, 2016, https://clinicaltrials.gov/ct2/show/NCT02676089?term=NCT02676089&draw=2&rank=1