Comparative evaluation on the synergism of roflumilast (RFL) and glycopyrronium (Gly) vs ciclesonide (CLS) and Gly on lung volumes and exercise tolerance in severe COPD

Abstract

Introduction: In severe COPD two classes of anti-inflammatory agents can be associated to a bronchodilator: inhibitors of phosphodiesterase-4 (PDE-4) and inhaled corticosteroids (ICS). It has been demonstrated a different effect on inflammation when a LAMA is associated to a PDE-4 inhibitor or to an ICS. Objective: This prospective interventional phase III pilot study aims to investigate whether RFL+Gly provides a greater bronchodilation vs to CLS+Gly in severe COPD. Secondary endpoint was to evaluate which combination between RFL+Gly or CLS+Gly had a greater effect on exercise capacity (endurance time and IC). Methods: 10 severe COPD patients performed PFTs, and Endurance Shuttle Walk Test (ESWT) (at 85% of an Incremental SWT) at time 0 (v1) after 2 weeks of gly (v2) and after 4 weeks (v3) of either RFL+Gly (5 subjects) or CLS+Gly (5 subjects). ICs were measured at rest and at the end of each ESWT. Lung volumes and distance were evaluated. Results: The RFL+Gly walked a longer distance at the ESWT than CLS+Gly ( Δ DistanceV2_V3: 56m ±82 vs –58m ±69, p Δ FEV1_V2_V3: 0,15L ±0,08 vs – 0,14L ±0,19, p Δ IC_V2_V3 at rest: 0,16L ±0,13 vs – 0,21L ±0,30, p Δ IC_V2_V3 at peak: 0,18L ±0,24 vs – 0,03L ±0,24, p=0,2). Conclusion: This is the first study to show that the choice of an anti-inflammatory agent (PDE4 inhibitor/ICS) associated to a LAMA may have different effects on lung volume and exercise tolerance; suggesting that RFL have a synergic interaction with Gly.