Triple Therapy in COPD in Real Life: Is It Better to Use Single or Multiple Inhalers?

Abstract

Background: Today, single-inhaler ICS/LAMA/LABA (SITT) COPD therapies are available. It is unclear whether they are more effective than multiple-device triple therapies (MITT) in improving COPD outcomes. Methods: We retrospectively considered patients on SITT/MITT in 2019/2020 who were prescribed >7 packages of ICS/LABA/LAMA or ICS/LAMA (+LAMA). The two treatments were compared concerning systemic corticosteroids, antibiotics, salbutamol, antifungal prescriptions, and number of emergency room visits/hospitalizations (ERV/Hs). We studied 292 MITT patients (Group A) during 2019, switching to SITT in 2020, and 366 subjects (Group B) who took SITT during 2019, and 206 MITT individuals (Group C) in 2020. Results: ICS/LABA + LAMA (MITT) package use was 8.2 ± 4.2 and 7.85 ± 4 in 2019, switching to 11.2 ± 3.2 when patients shifted to SITT in 2020 (p = 0.0001). Group A MITT package use was lower than in SITT patients in 2019 (9.31 ± 2.71, p = 0.0001; Group B). Throughout 2020, Group C (10.3 ± 6.1 packs) adherence to ICS/LABA was similar to SITT adherence in Group A (p = 0.270), whereas LAMA package use (9.1 ± 5) was lower (p = 0.0038). Patients using systemic corticosteroids/antibiotics were fewer in SITT in 2020, compared to the MITT results in 2019. Subjects with fewer ERV/Hs were observed with SITT rather than with MITT. Particularly, 13.8% of patients needed ≥2 ERV/Hs when treated with SITT, whereas 19.2% needed ≥2 ERV/Hs with MITT in 2019 (p = 0.08). Multivariate analysis, adjusted for all confounding factors including treatment adherence, showed that MITT (vs. SITT) can have an increased risk of at least one ERV/H (subjects receiving MITT during 2019 passing to SITT in 2020, OR: 1.718 [1.010-2.924], p = 0.046; Group A/MITT/2019 vs. Group B/SITT/2019, OR: 1.650 [0.973-3.153], p = 0.056; Group C/MITT/2020 vs. Group B/SITT/2019, OR: 1.908 [1.018-3.577], p = 0.044). Conclusions: SITT therapy may promote treatment adherence more effectively, therefore, reducing COPD exacerbations better than MITT. A possible synergistic effect of ICS/LABA/LAMA intake with a single device might be another cause of SITT's greater efficacy.

Keywords: COPD; antibiotics; exacerbations; multiple inhalers; oral corticosteroids; short-acting beta2 agonists; single inhaler; triple therapy.

Figure 1

Study protocol. Patients treated with triple therapy with multiple devices (MITT) and with triple therapy with single devices (SITT). Inhaled corticosteroids (ICS), long-acting β2 agonist (LABA) and long-acting muscarinic antagonist (LAMA). SITT: ICS/LABA/LAMA (single inhaler); MITT: ICS/LABA + LAMA (triple therapy consisting of two devices, one for ICS/LABA and the other for LAMA).

Figure 2

Adherence (number of packages/year) observed in the different groups treated with triple therapy with multiple devices (MITT) and with triple therapy with single devices (SITT) in 2019 or 2020.

Figure 3

Percentages of subjects who had had at least one prescription of systemic corticosteroids, antibiotics, SABA (short-acting β2-agonist), and antifungal packages during 2019 and 2020 in the various groups considered.

Figure 4

Percentages of subjects who had one or at least two emergency department visits/hospitalizations during one year of MITT or SITT therapy (2019 or 2020) in the various groups considered.

Figure 5

Logistic regression models that compared the effects (on different outcomes) of the treatment with triple therapy with multiple inhalers performed in 2019 and triple therapy with single inhalers prescribed in 2020 in the same subjects (Group A); The figure shows the odds ratios with a 95% confidence interval (OR [95% CI]).

Figure 6

Logistic regression models that compared the effects (on different outcomes) of the treatment with triple therapy with multiple inhalers prescribed in Group A in 2019 and triple therapy with single inhalers in Group B in 2019; The figure shows the odds ratios with a 95% confidence interval (OR [95% CI]).

Figure 7

Logistic regression models that compared the effects (on different outcomes) of the treatment with triple therapy with single inhalers prescribed in Group B in 2019 and triple therapy with multiple inhalers in Group C in 2020; The figure shows the odds ratios with a 95% confidence interval (OR [95% CI]).