RCT Abstract - Airway smooth muscle mass to predict response to ICS in COPD patients receiving triple therapy (HISTORIC study): a randomized, placebo-controlled, double-blind, investigator-initiated trial

In contrast to asthma, ICS are clinically effective only in selected COPD patients. We hypothesised that increased ASMC mass predicts response to ICS in COPD patients receiving triple therapy. 201 COPD patients (65 females, GOLD B-D, ≥1 AECOPD in the previous year) were divided in 2 groups with high (>20%) and low (≤20%) ASMC mass based on histological analysis of endobronchial biopsies. All patients followed a run-in period of 6 weeks on open-label triple therapy with aclidinium (ACL, 400 mcg/bid), formoterol (FOR, 12mcg/bid) and budesonide (BUD, 400 mcg/bid). Subsequently, patients from each group were randomized (1:1) to receive either ACL/FOR/BUD or ACL/FOR/Placebo. The primary end point of the study was the difference in post-bronchodilator FEV1 at 12 months between patients with low and high ASMC mass, receiving or not ICS. In COPD patients with low ASMC, ACL/FOR/BUD did not significantly improve FEV1 over 12 months, as compared to ACL/FOR/placebo [adjusted mean (95% CI): -0.110 ml/day (-0.310 to 0.091) and -0.248 (-0.454 to 0.042), respectively], p=0.675. In patients with high ASMC, however, ACL/FOR/BUD significantly improved FEV1, as compared to ACL/FOR/placebo [0.187 ml/day (-0.075 to 0.449) and -0.314 (-0.569 to -0.059), respectively], p=0.020. Over 12 months, the difference of FEV1 change between the groups of ACL/FOR/BUD and ACL/FOR/placebo was 0.138 ml/day (50.4 ml/year) for patients with low ASMC (p=0.345) and 0.501 ml/day (183.0 ml/year) for patients with high ASMC (p=0.008). In conclusion, high ASMC mass appears to predict ICS response in COPD patients receiving triple therapy.