LANTERN: a randomized study of QVA149 versus salmeterol/fluticasone combination in patients with COPD

Abstract

BackgroundThe current Global initiative for chronic Obstructive Lung Disease (GOLD) treatment strategy recommends the use of one or more bronchodilators according to the patient’s airflow limitation, their history of exacerbations, and symptoms. The LANTERN study evaluated the effect of the long-acting β2-agonist (LABA)/long-acting muscarinic antagonist (LAMA) dual bronchodilator, QVA149 (indacaterol/glycopyrronium), as compared with the LABA/inhaled corticosteroid, salmeterol/fluticasone (SFC), in patients with moderate-to-severe COPD with a history of ≤1 exacerbation in the previous year.MethodsIn this double-blind, double-dummy, parallel-group study, 744 patients with moderate-to-severe COPD with a history of ≤1 exacerbations in the previous year were randomized (1:1) to QVA149 110/50 μg once daily or SFC 50/500 μg twice daily for 26 weeks. The primary endpoint was noninferiority of QVA149 versus SFC for trough forced expiratory volume in 1 second (FEV1) at week 26.ResultsOverall, 676 patients completed the study. The primary objective of noninferiority between QVA149 and SFC in trough FEV1 at week 26 was met. QVA149 demonstrated statistically significant superiority to SFC for trough FEV1 (treatment difference [Δ]=75 mL; P<0.001). QVA149 demonstrated a statistically significant improvement in standardized area under the curve (AUC) from 0 hours to 4 hours for FEV1 (FEV1 AUC0–4h) at week 26 versus SFC (Δ=122 mL; P<0.001). QVA149 and SFC had similar improvements in transition dyspnea index focal score, St George Respiratory Questionnaire total score, and rescue medication use. However, QVA149 significantly reduced the rate of moderate or severe exacerbations by 31% (P=0.048) over SFC. Overall, the incidence of adverse events was comparable between QVA149 (40.1%) and SFC (47.4%). The incidence of pneumonia was threefold lower with QVA149 (0.8%) versus SFC (2.7%).ConclusionThese findings support the use of the LABA/LAMA, QVA149 as an alternative treatment, over LABA/inhaled corticosteroid, in the management of moderate-to-severe COPD patients (GOLD B and GOLD D) with a history of ≤1 exacerbation in the previous year.

Indacaterol/glycopyrronium in symptomatic patients with COPD (GOLD B and GOLD D) versus salmeterol/fluticasone: ILLUMINATE/LANTERN pooled analysis

“…In both the GOLD B and GOLD D subgroups, dual bronchodilation with IND/GLY demonstrated superior improvement in trough FEV 1 , weighted mean FEV 1 from 0 to 12 hours and peak FEV 1 versus SFC. These findings are consistent with previously reported trials, where IND/GLY showed a significant improvement in lung function versus SFC 6,7. Treatment differences in all the lung function parameters between IND/GLY and SFC were clinically significant in the overall pooled population and also in patients belonging to the GOLD B and GOLD D subgroups, except pre-dose trough FEV 1 in the GOLD D subgroup (treatment difference, 80 mL).…”

“…This was not unexpected, since a similar finding was observed in the LANTERN,7 ILLUMINATE,6 and UMEC/VI (umeclidinium/vilanterol) versus SFC8 studies. Moreover, neither studies included in the analysis was powered to show the treatment differences in terms of patient-reported outcomes.…”

“…Although this study was conducted in a population that was largely not at high risk for exacerbation, IND/GLY showed a reduction in the number of exacerbations within the overall pooled population as well as in patients belonging to subgroups GOLD B and GOLD D. In the LANTERN study, the reduction in the rate and risk of moderate or severe exacerbations was significant with IND/GLY versus SFC in COPD patients with ≤1 exacerbation in the previous year,7 whereas, in a post hoc analysis of the ILLUMINATE study, IND/GLY and SFC showed comparable results in patients without exacerbations in the previous year 12. Although the rates of exacerbation were low in this analysis, our findings are further supported by the results of the FLAME study that showed superior efficacy of IND/GLY versus SFC in terms of decreasing the risk of exacerbation (primary objective) and improving the lung function and quality of life over 52 weeks of treatment in COPD patients with a risk of exacerbation 10…”

“…These studies are registered at ClinicalTrials.gov with clinical trial identifier number NCT01315249 (ILLUMINATE) and NCT01709903 (LANTERN). The study details and primary outcomes have been published previously 6,7. Following the screening and run-in periods, eligible patients were randomized (1:1) to IND/GLY 110 μg/50 μg OD (via the Breezhaler ® device) or SFC 50 μg/500 μg twice daily (via the Accuhaler ® device) during the 26-week, double-blind treatment period followed by a 30-day safety follow-up.…”

“…The ILLUMINATE study previously demonstrated the superiority of IND/GLY compared with salmeterol/fluticasone (SFC), a LABA/ICS combination, in patients with moderate-to-severe COPD without a history of moderate or severe exacerbation in the previous year 6. Furthermore, the LANTERN study confirmed superior bronchodilation with IND/GLY versus SFC, along with reduction in the rates of moderate or severe exacerbation in moderate-to-severe COPD patients with a history of ≤1 exacerbation in the previous year 7. Despite increasing evidence that combining bronchodilators of different pharmacological classes provides additional benefit over the use of a single agent and LABA/ICS combination, within the GOLD strategy, dual bronchodilation with a LABA/LAMA is classed as an alternative treatment choice for patients whose symptoms are inadequately controlled with monotherapy.…”