Contrary to GOLD recommendations, patients at low risk of exacerbation and moderate airflow limitation are frequently prescribed inhaled corticosteroids. 1 Recent data from INSTEAD showed that patients with moderate COPD and no exacerbations in the previous year can be switched from SFC 50/500µg BID to indacaterol 150µg with no efficacy decrease. 2 Exploratory symptom efficacy data are presented here. Methods were published previously. 2 Patients recorded morning/evening daily respiratory symptoms, cough, wheezing, sputum volume and colour, breathlessness, sore throat, cold and fever. This analysis was a prespecified exploratory objective. The percentage of nights with no night-time awakenings, days with no daytime symptoms, and days able to perform usual daily activities were calculated over 12 and 26 wks treatment, as were mean individual diary symptom scores. There were no statistically significant differences between indacaterol and SFC for any variable, illustrated in Table 1. Patients at low risk of exacerbation can be switched from SFC to indacaterol with no deterioration in symptoms or symptoms scores. Vestbo J et al Respir Med 2014;108:729-36 Rossi A et al ERJ 2014;44:1548-56

Introduction There is a high unmet need for safe, effective and convenient therapies to control symptoms and reduce the impact of exacerbations in severe asthma. Eosinophilic inflammation is common in asthma and attenuation of sputum eosinophilia is strongly associated with reduced exacerbation frequency. Methods In this single-center, double-blind, randomized controlled study, asthmatics (GINA II-V), with a sputum eosinophil count ≥2% at baseline, were randomised to QAW039 225mg BID or placebo for 12 weeks after a 2-week placebo run-in. The primary endpoint was the reduction of sputum eosinophils. Secondary, exploratory and post-hoc outcomes included changes in Asthma Control Questionnaire score (ACQ7), Asthma Quality of Life score (AQLQ) and FEV1. Results 61 patients were randomized (30 to QAW039 and 31 to placebo); 90% were ≥GINA IV; and 25% were GINA V requiring up to 10 mg prednisolone daily. The primary endpoint was met, with QAW039 reducing sputum eosinophils 3.5-fold over placebo (95% CI: 1.7-7.0, p=0.001). The AQLQ improved in those treated with QAW039 compared to placebo (0.59 points; p=0.008) with non-significant improvements in ACQ7 in the group as a whole (0.40 points; p=0.084), which was greater in those with poor asthma control (ACQ≥1.5) at baseline (0.56 points; p=0.046). FEV1 improved in those receiving QAW039 versus placebo (0.074L; p=0.408; pre-bronchodilator (BD), 0.163L; p=0.022; post-BD). AEs were mild/moderate, balanced between both groups with no SAEs or deaths. Conclusion QAW039 is effective at attenuating eosinophilic airway inflammation, improves health status and lung function and has a favourable safety profile.

Introduction Many patients with low risk of COPD exacerbations receive twice-daily (bid) LABA/ICS, salmeterol/fluticasone (SFC), for maintenance treatment. This study evaluated the effect of switching these patients to a once-daily (od) LABA, indacaterol, monotherapy. Methods INSTEAD was a 26-week double-blind, double-dummy study in patients aged ≥40 years, with moderate COPD (post-bronchodilator FEV1 50–80% predicted) and no exacerbations in the past 12 months, who were receiving SFC 50/500 μg bid for ≥3 months prior to study entry. Patients were randomised (1:1) to continue with SFC 50/500 μg or to be switched (with no washout) to indacaterol 150 μg. The primary objective was to demonstrate non-inferiority of indacaterol to SFC, measured by trough FEV1 after 12 weeks (non-inferiority margin: 60 mL). Trough FEV1 was also evaluated at 4, 8 and 26 weeks. TDI and SGRQ-C total scores were evaluated at Weeks 12 and 26; the annualised rate of exacerbations and safety were evaluated over 26 weeks. Results A total of581 patients were randomised (indacaterol: 293; SFC: 288); 85.4% completed the study. The primary endpoint was met, with a LSM difference in trough FEV1 between indacaterol and SFC of –9 mL (95% CI: –45 to 26 mL; p = 0·002 for NI). There were no significant differences between treatments in trough FEV1 at any of the other visits (Baseline and Weeks 4, 8 and 26). The TDI and SGRQ-C total scores and their responder rates were similar between two treatments, at both Weeks 12 and 26 (Table 1). During the 26 week treatment period, 79.5% and 74.7% of patients in the indacaterol and SFC groups, respectively, experienced no exacerbations. There was no statistically significant difference between treatments in the rate of all COPD exacerbations per year, with rates of 0.57 vs 0.67, respectively (RR 0.86 [95% CI 0.62, 1.20]; p = 0.367). Adverse events (AEs) and serious AEs were comparable between the treatment arms. Conclusion Indacaterol was non-inferior to SFC in terms of bronchodilation and showed similar efficacy in terms of breathlessness, health status, and exacerbation rate indicating that this group of patients can be switched from SFC to indacaterol 150 µg with no loss in efficacy.

The Indacaterol: Switching Non-exacerbating Patients with Moderate COPD From Salmeterol/Fluticasone to Indacaterol (INSTEAD) study investigated the effect of switching patients at low risk of chronic obstructive pulmonary disease (COPD) exacerbations from salmeterol/fluticasone (SFC; inhaled corticosteroid (ICS) regimen) to indacaterol monotherapy (non-ICS regimen). This 26-week, double-blind, double-dummy, parallel-group, phase IV study, randomised 581 patients with moderate COPD to indacaterol 150 μg once daily or SFC 50/500 μg twice daily. Patients had been receiving SFC 50/500 μg for ≥3 months, with no COPD exacerbations for more than a year before the study (patients for whom ICS is not recommended). The primary objective was to demonstrate non-inferiority of indacaterol to SFC, measured by trough forced expiratory volume in 1 second (FEV 1 ) after 12 weeks (non-inferiority margin of 0.06 L). The primary objective was met, with a mean treatment difference of 9 mL (95% CI -45–26 mL). There were no significant differences between treatments in terms of breathlessness (transition dyspnoea index) or health status (Saint George’s Respiratory Questionnaire) at weeks 12 or 26, or rescue medication use or COPD exacerbation rates over 26 weeks. Safety profiles of both treatments were as expected. This study demonstrated that patients with moderate COPD and no exacerbations in the previous year can be switched from SFC to indacaterol 150 μg with no efficacy loss.