Treatment response in COPD: does FEV1 say it all? A post hoc analysis of the CRYSTAL study

Konstantinos Kostikas; Timm Greulich; Alexander J Mackay; Nadine S Lossi; Maryam Aalamian-Mattheis; Xavier Nunez; Veronica A Pagano; Francesco Patalano; Andreas Clemens; Claus F Vogelmeier

doi:10.1183/23120541.00243-2018

Treatment response in COPD: does FEV₁ say it all? A post hoc analysis of the CRYSTAL study

ERJ Open Res. 2019 Feb 25;5(1):00243-2018. doi: 10.1183/23120541.00243-2018. eCollection 2019 Feb.

Authors

Affiliations

¹ Respiratory Medicine Dept, University of Ioannina, Ioannina, Greece.
² Dept of Medicine, Pulmonary and Critical Care Medicine, University Medical Center Giessen and Marburg, Philipps-Universität Marburg, Member of the German Center for Lung Research (DZL), Giessen, Germany.
³ Airways Disease Section, National Heart and Lung Institute, Imperial College London, London, UK.
⁴ Novartis Pharma GmbH, Nuremberg, Germany.
⁵ Novartis Pharma AG, Basel, Switzerland.
⁶ TFS Develop, Barcelona, Spain.
⁷ Dept of Cardiology and Angiology I, Heart Center Freiburg University, Faculty of Medicine, University of Freiburg, Freiburg, Germany.
⁸ These two authors contributed equally to this work.

Abstract

The association between clinically relevant changes in patient-reported outcomes (PROs) and forced expiratory volume in 1 s (FEV₁) in patients with chronic obstructive pulmonary disease (COPD) has rarely been investigated. Using CRYSTAL, a 12-week open-label study in symptomatic, nonfrequently exacerbating patients with moderate COPD, we assessed at baseline the correlations between several PROs (Baseline Dyspnoea Index, modified Medical Research Council dyspnoea scale, COPD Assessment Test (CAT) and Clinical COPD Questionnaire (CCQ)), and between FEV₁ and PROs. Associations between clinically relevant responses in FEV₁, CAT, CCQ and Transition Dyspnoea Index (TDI) at week 12 were also assessed. Using data from 4324 patients, a strong correlation was observed between CAT and CCQ (r_s=0.793) at baseline, with moderate or weak correlations between other PROs, and no correlation between FEV₁ and any PRO. At week 12, 2774 (64.2%) patients were responders regarding TDI, CAT or CCQ, with 583 (13.5%) responding using all three measures. In comparison, 3235 (74.8%) were responders regarding FEV₁, TDI, CAT or CCQ, with 307 (7.1%) responding concerning all four parameters. Increases in lung function were accompanied by clinically relevant improvements of PROs in a minority of patients. Our results also suggest that PROs are not interchangeable. Thus, the observed treatment success in a clinical trial may depend on the selected parameters.