Reduced risk of clinically important deteriorations by ICS in COPD is eosinophil dependent: a pooled post-hoc analysis

Abstract

Background: Clinically Important Deterioration (CID) is a novel composite measure to assess treatment effect in chronic obstructive pulmonary disease (COPD). We examined the performance and utility of CID in assessing the effect of inhaled corticosteroids (ICS) in COPD. Methods: This post-hoc analysis of four budesonide/formoterol (BUD/FORM) studies comprised 3576 symptomatic moderate-to-very-severe COPD patients with a history of exacerbation. Analysis of time to first CID event (exacerbation, deterioration in forced expiratory volume in 1 second [FEV 1 ] or worsening St George's Respiratory Questionnaire [SGRQ] score) was completed using Cox proportional hazards models. Results: The proportion of patients with ≥1 CID in the four studies ranged between 63 and 77% and 69-84% with BUD/FORM and FORM, respectively, with an average 25% reduced risk of CID with BUD/FORM. All components contributed to the CID event rate. Experiencing a CID during the first 3 months was associated with poorer outcomes (lung function, quality of life, symptoms and reliever use) and increased risk of later CID events. The effect of BUD/FORM versus FORM in reducing CID risk was positively associated with the blood eosinophil count. Conclusions: Our findings suggest that BUD/FORM offers protective effects for CID events compared with FORM alone, with the magnitude of the effect dependent on patients' eosinophil levels. CID may be an important tool for evaluation of treatment effect in a complex, multifaceted, and progressive disease like COPD, and a valuable tool to allow for shorter and smaller future outcome predictive trials in early drug development.

Modified and simplified clinically important deterioration: multidimensional indices of short-term disease trajectory to predict future exacerbations in patients with chronic obstructive pulmonary disease

“… 11 Until now, there were no prospective studies conducted to validate the predictive value of CID, though several studies had used this composite index as outcome or endpoint. 12 , 13 , 25 , 26 To make the CID model more practical in clinical application, we replaced SGRQ with the CAT questionnaire, since CAT and the change of CAT had close correlation to SGRQ. 16 Then we assessed the predictive capacity of CID-C for future exacerbation.…”

“… 11 Some researchers also set up the first time to CID over 6 months or the CID status at the sixth month as the endpoint of their studies to assess and quantify individual levels of disease deterioration. 12 , 13 However, none of those studies were prospectively designed to assess the prediction value of CID for COPD outcomes.…”

Einbeziehung von Komorbiditäten und phänotypbasierter Medizin beim patientenzentrierten COPD-Management

“…Verschiedene Studien haben die mögliche Bedeutung der Eosinophilen im Blut bei der Auswahl von Patienten für bestimmte Behandlungen [26, 27, 28, 29] mit biologischem Hintergrund unterstrichen [30]. Allerdings ist die Zahl der Eosinophilen im Blut nicht spezifisch, da sie eine schwache Korrelation mit der eosinophilen Entzündung aufweist und die Eosinophilie bei COPD-Patienten andere Ursachen haben kann [31, 32, 33].…”

Integrating Comorbidities and Phenotype-Based Medicine in Patient-Centered Medicine in COPD

“…Different studies have highlighted the potential role of blood eosinophils in patient selection for specific treatments [ 26 , 27 , 28 , 29 ] with a biological background [ 30 ]. However, the blood eosinophil count is nonspecific, since it has a weak correlation with eosinophilic inflammation and there are other causes of eosinophilia in COPD patients [ 31 , 32 , 33 ].…”