Patients with stable COPD and infrequent exacerbations can de-escalate from triple therapy to dual bronchodilator therapy with minimal change to lung function and no change to exacerbation rates.
According to research presented at ATS 2018 and published in the American Journal of Respiratory and Critical Care Medicine, removing the inhaled corticosteroid from triple therapy was fine for all but the minority of patients (15%) with an elevated blood eosinophil count.
The randomised controlled SUNSET trial, funded by Novartis, involved 1,053 patients on triple therapy for a minimum of six months then either maintained on their existing regimen – tiotropium plus salmeterol/fluticasone – or switched to once-daily indacterol and glycopyrronium.
Treatment de-escalation led to a small but significant decrease in lung function of 26 mL in trough FEV1 but with no difference in the rate of COPD exacerbations or time to next exacerbation.
Only patients with blood eosinophils ≥300 cells/uL at baseline showed a bigger change in FEV1 and an increase in their exacerbation rate.
Adverse events and serious adverse events were similar in both patient groups.
“Our study answers the clinically relevant question of how to manage patients who are on triple therapy started under previous recommendations (e.g. FEV1 <50% predicted and/or ≥2 exacerbations in the previous year according to GOLD 2011) or those who have been inappropriately escalated,” the study said.
It said the observed reduction of 26 mL with de-escalation was consistent with the small benefit in lung function seen with the use of inhaled corticosteroids.
The findings were also consistent with other studies showing that ICS discontinuation was safe in the presence of effective long-acting bronchodilator in appropriate patients.
“Several studies of COPD populations suggest that only about 20% are exacerbation-prone and might therefore benefit from inhaled corticosteroid use as part of their treatment,” co-author Dr Kenneth Chapman said.
“Given emerging concerns about inhaled corticosteroid side effects, the SUNSET trial should encourage physicians to focus on the dual bronchodilator foundation of COPD pharmacotherapy for the majority of their patients and reserve ‘triple therapy’ for the minority who suffer frequent exacerbations, particularly if the blood eosinophil count is persistently elevated.”
Dr Chapman told the limbic that the SUNSET and recent IMPACT trials describe the same problem from opposite ends of the spectrum.
“IMPACT reconfirmed that frequently exacerbating COPD patients benefit when ICS is added to a dual bronchodilator therapy. SUNSET reassured that it was safe to step away from ICS in the majority of COPD patients who don’t exacerbate frequently.”
“We are concerned that the use of triple will be ‘oversold’ and that many patients will be exposed to the risk of long term risks of ICS needlessly.”