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Dropping ICS does not increase exacerbation risk in moderate-to-severe COPD

Roshini Claire Anthony
02 Jun 2018

De-escalating treatment from triple therapy (LABA*/LAMA**/inhaled corticosteroid [ICS]) to dual bronchodilator therapy (indacaterol/glycopyrronium) did not increase exacerbation rate, though there was a minor decrease in lung function in patients with moderate-to-severe chronic obstructive pulmonary disease (COPD) with infrequent exacerbations, according to results of the SUNSET*** trial presented at the recent American Thoracic Society conference (ATS 2018).

“We have shown that the treatment de-escalation led to a small but significant decrease in lung function … with no difference in the rates or risk of COPD exacerbations between treatments,” said the authors led by Professor Kenneth Chapman from the University of Toronto, Ontario, Canada.

Following a 4-week run-in period on triple therapy (tiotropium 18 µg QD plus salmeterol/fluticasone propionate 50/500 µg BID), 1,053 patients (mean age 65.3 years, 70.6 percent male, mean post-bronchodilator FEV1# 1.6 L) with moderate-to-severe COPD with infrequent exacerbations (≤1 moderate or severe exacerbation in the previous year) were randomized to either continue triple therapy (n=526) or were de-escalated to indacaterol/glycopyrronium (110/50 µg QD; n=527) for 26 weeks.

To qualify, patients needed to have received long-term triple therapy (≥6 months prior to study enrolment), have a post-bronchodilator FEV1 of ≥40 percent to <80 percent predicted, a post-bronchodilator FEV1:FVC## ratio of <0.70, and a ≥10 pack-year smoking history, while those with blood eosinophil counts of >600 cells/µL or a history of asthma were excluded.

The withdrawal of ICS led to a mean reduction from baseline in post-dose trough FEV1 of -26 mL (95 percent confidence interval [CI], -53 to 1 mL) between the indacaterol/glycopyrronium and triple therapy groups at week 26. [Am J Respir Crit Care 2018;doi:10.1164/rccm.201803-0405OC; ATS 2018, abstract A1009]

The annualized rate of moderate or severe COPD exacerbations was comparable between patients on indacaterol/glycopyrronium and triple therapy (0.52 vs 0.48, rate ratio [RR], 1.08, 95 percent CI, 0.83–1.40), as was the rate of all exacerbations (4.11 vs 3.86, RR, 1.07, 95 percent CI, 0.93–1.22) and time to first moderate or severe exacerbation (hazard ratio, 1.11, 95 percent CI, 0.85–1.46).

Patients whose baseline blood eosinophil levels were ≥300 cells/µL appeared to have an elevated risk of exacerbations upon withdrawal of ICS (RR, 1.86, 95 percent CI, 1.06–3.29).

“[W]e were also able to identify that the patients at higher risk for more prominent loss of lung function were those with higher blood eosinophils [mean reduction of -69 mL in patients with ≥300 cells/µL],” said Chapman and co-authors. “[T]hese patients are more likely to benefit from continuing triple therapy.”

Adverse event (AE) and severe AE incidence was comparable between patients on indacaterol/glycopyrronium and triple therapy (80.8 percent vs 82.5 percent and 6.1 percent vs 6.5 percent, respectively), as was the incidence of AE-related drug discontinuations (3.6 percent vs 3.4 percent).

Although current recommendations advise against triple therapy in patients with COPD with low risk of exacerbations, these recommendations are not always followed, bringing with them the potential for AEs due to long-term ICS use. [Int J Chron Obstruct Pulmon Dis 2017;12:73-83]

“[While] it still remains unclear which patients will benefit from ICS on top of LABA/LAMA, our study adds evidence … as to which COPD patients can have ICS safely withdrawn from long-term triple therapy, suggesting that these are the non-frequently exacerbating patients with blood eosinophil counts <300 cells/μL,” said the authors.

“The results of the SUNSET study provide evidence for the personalized management of COPD patients,” they said.

They cautioned that these findings are specific to the second-generation LABA/LAMA combination of indacaterol and glycopyrronium and thus, may not apply to other bronchodilators. The short treatment duration also did not allow for determination of long-term AEs.

 

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