Treatment response in COPD – does FEV1 say it all? An analysis of the CRYSTAL trial

Rationale Improvements in FEV₁ correlate with patient-related outcomes (PROs) at a population level (Donohue et al. Pulm Pharm Ther. 2018). However, the association of clinically relevant changes in PROs with changes in FEV₁ in individual patients have seldom been investigated.

Methods CRYSTAL, a 12-week, prospective, randomised, pragmatic trial, evaluated the effect of indacaterol/glycopyrronium (IND/GLY) or GLY after direct switch from previous treatments in moderate COPD patients. Lung function (FEV₁), COPD assessment test (CAT), clinical COPD questionnaire (CCQ) and Transitional Dyspnoea Index (TDI) were evaluated after 12 weeks vs. baseline.

Results Of 4324 patients 2774 (64.2%) were classified as responders by TDI, CAT or CCQ with 1365, 826 and 583 patients responding according to 1, 2 or all 3 PROs respectively. In comparison, 3235 patients (74.8%) were considered responders when combining TDI, CAT, CCQ and FEV₁ and 1555 patients (36%) responded to PROs only (≥ 1) but not to FEV₁. Out of 1680 responders to FEV₁, 1219 (72.6%) patients demonstrated a combined response (FEV₁ and ≥ 1 PRO), and 461 (27.4%) showed only a response in FEV₁. There was little overlap between responders to TDI, CAT, CCQ and FEV₁ ([Fig. 1]).

Conclusions Improvements in lung function do not always translate into improvements in PROs in individual patients. PROs are not interchangeable and hence the definition of treatment success depends on the PRO used.