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

<b>Background:</b> 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. <b>Methods</b>: 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. <b>Results:</b> 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 (<i>p</i> = 0.0001). Group A MITT package use was lower than in SITT patients in 2019 (9.31 ± 2.71, <i>p</i> = 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 (<i>p</i> = 0.270), whereas LAMA package use (9.1 ± 5) was lower (<i>p</i> = 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 (<i>p</i> = 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], <i>p</i> = 0.046; Group A/MITT/2019 vs. Group B/SITT/2019, OR: 1.650 [0.973-3.153], <i>p</i> = 0.056; Group C/MITT/2020 vs. Group B/SITT/2019, OR: 1.908 [1.018-3.577], <i>p</i> = 0.044). <b>Conclusions:</b> 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.