Differential Outcomes Following 4 Weeks of Aclidinium/Formoterol in Patients with COPD: A Reanalysis of the ACTIVATE Study

M. Koopman*, F.M.E. Franssen, S. Gaffron, H. Watz, T. Troosters, J. Garcia-Aymerich, P. Paggiaro, E. Molins, M. Moya, L. van Burk, D. Maier, E.G. Gil, E.F.M. Wouters, L.E.G.W. Vanfleteren, M.A. Spruit

*Corresponding author for this work

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Rationale: It is difficult to predict the effects of long-acting bronchodilators (LABD) on lung function, exercise capacity and physical activity in patients with chronic obstructive pulmonary disease (COPD). Therefore, the multidimensional response to LABD was profiled in COPD patients participating in the ACTIVATE study and randomized to LABD.Methods: In the ACTIVATE study, patients were randomized to aclidinium bromide/formoterol fumarate ( AB/FF) or placebo for four weeks. The primary outcomes included (1) lung function as measured by functional residual capacity (FRC), residual volume (RV), and spirometric outcomes; (2) exercise performance as measured by a constant work rate cycle ergometry test (CWRT); and (3) physical activity (PA) using an activity monitor. Self-organizing maps (SOMs) were used to create an ordered representation of the patients who were randomly assigned to four weeks of AB/FF and cluster them into different outcome groups.Results: A total of 250 patients were randomized to AB/FF (n = 126) or placebo (n = 124). Patients in the AB/FF group (39.6% women) had moderate-to-severe COPD, static hyperinflation (FRC: 151.4 (27.7)% predicted) and preserved exercise capacity. Six clusters with differential outcomes were identified. Patients in clusters 1 and 2 had significant improvements in lung function compared to the remaining AB/FF-treated patients. Patients in clusters 1 and 3 had significant improvements in CWRT time, and patients in clusters 2, 3 and 6 had significant improvements in PA compared to the remaining AB/FF-treated patients.Conclusion: Individual responses to 4 weeks of AB/FF-treatment in COPD are differential and the degree of change differs across domains of lung function, exercise capacity and PA. These results indicate that clinical response to LABD therapy is difficult to predict and is non-linear, and show doctors that it is important to look at multiple outcomes simultaneously when evaluating the clinical response to LABD therapy.
Original languageEnglish
Pages (from-to)517-533
Number of pages17
JournalInternational journal of chronic obstructive pulmonary disease
Publication statusPublished - 2022


  • COPD
  • hyperinflation
  • physical activity

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