Step-down therapy may be the better strategy for certain COPD patients

Switching from triple therapy to dual bronchodilation in patients with chronic obstructive pulmonary disease (COPD) improves symptom control in a new analysis of the DACCORD study.

Dropping the inhaled corticosteroid (ICS) component in the triple therapy led to fewer adverse events, reported study author Dr Claus Vogelmeier from University Medical Center Giessen and Philipps-University Marburg in Marburg, Germany at ATS 2022.

Half of the patients who switched to dual bronchodilation experienced a new COPD exacerbation only after 14 months vs 9.5 months in those who stayed on triple therapy (an ICS, a long-acting β₂-agonist (LABA), and a long-acting muscarinic antagonist (LAMA), taken in combination).

On top of these benefits, more patients in the dual therapy group had clinically relevant improvement in COPD Assessment Test (CAT) scores. [ATS 2022, abstract C93]

What it means for clinicians

The take-home message, Vogelmeier shared, is that switching from triple to dual therapy did not worsen COPD symptoms. On the contrary, the step-down approach resulted in better COPD outcomes. “Additionally, the finding suggests that in a real-world setting, clinicians are actually capable of identifying which patients can be safely stepped down from triple therapy.”

Guidelines for COPD recommend inhaled triple therapy with ICS/LABA/LAMA as a stepped-up therapy for individuals who experience recurrent exacerbations (acute worsening of symptoms), persistent breathlessness, or exercise limitation despite dual therapy.

But while ICS agents cause fewer side effects than systemic steroids, they still carry some risks. For patients achieving reasonable symptom control with triple therapy, research has questioned whether a LABA/LAMA combination would be sufficient.

Switch or stay

The current study analysed data from the third cohort of German COPD patients in the DACCORD study that was followed until 2021 from 2017.

Patients included 340 who switched to a fixed-dose LABA/LAMA therapy and 784 who stayed on triple therapy. Those who remained on triple therapy were mostly male, with longer disease duration, and poorer lung function.

The most common reason cited by patients for staying on triple therapy was COPD symptom control (35 percent) and patient wish (26 percent) for those switching. Very few patients switched because “triple therapy wasn’t working or had intolerable side effects.”

Time to first COPD exacerbation was the primary endpoint.

The risk doubled with triple therapy

The 1-year risk was doubled among patients who stayed on triple therapy (hazard ratio [HR] 2.00). By 1 year,  almost 60 percent of those on triple therapy had experienced an exacerbation compared with about 35 percent of those who switched to dual therapy.

CAT scores at baseline averaged 21.0 in the switch group and 20.0 in the no-switch group. At 1 year, the scores were down by 2 points for switchers, suggesting improvement,  and by 1 point for non-switchers. Fifty-eight percent of patients who switched to dual therapy had clinically relevant improvement in scores vs 49 percent of non-switchers (p<0.001).

Looking at a sub-group of patients with a history of  ≥2 exacerbations prior to study enrolment,  over 60 percent of switchers had no exacerbations at follow-up vs fewer than half among those on triple therapy. Dual therapy also appeared safer.

When session moderator Dr Mark Dransfield from the University of Alabama, Birmingham, US asked if the data suggest that ICS therapy is “overtly harmful in COPD maintenance”, Vogelmeier admittedly said it is hard to tell. “What we do not know is how good the indication was for triple treatment to start with,” he added.

For patients who might be taking ICS maintenance unnecessarily, stepping down to a LABA/LAMA fixed-dose combination may be the better strategy for COPD.