Effect of Roflumilast and Inhaled Corticosteroid/Long-Acting β₂-Agonist on Chronic Obstructive Pulmonary Disease Exacerbations (RE²SPOND). A Randomized Clinical Trial

Abstract

Roflumilast failed to statistically significantly reduce moderate and/or severe exacerbations in the overall population. Roflumilast improved lung function and reduced exacerbations in participants with frequent exacerbations and/or hospitalization history. The safety profile of roflumilast was consistent with that of previous studies. Clinical trial registered with www.clinicaltrials.gov (NCT01443845).

Update in Chronic Obstructive Pulmonary Disease 2014

“…However, post hoc analysis did show a 39% reduction in exacerbation frequency with Roflumilast use, relative to placebo, among those who had experienced three or more exacerbation within the previous year (P=0.03) (Figure 1), supporting the results of the earlier published Roflumilast and Exacerbations in patients receiving Appropriate Combination Therapy (REACT) study (8). Those with very frequent exacerbations, who perhaps should be considered "super-exacerbators" (9), may therefore obtain particular benefit, perhaps because they have enhanced airway inflammation which responds to Roflumilast (9).…”

“…This study investigated the effect on exacerbation rate of adding Roflumilast to standard COPD care (8) enrolling patients with at least severe grade COPD, chronic bronchitis and two or more exacerbations within the preceding year. Roflumilast is a phosphodiesterase-4 inhibitor, known to reduce both neutrophilic and eosinophilic inflammation, which is already licensed for use in COPD patients with chronic bronchitis and FEV 1 <50% predicted.…”

Chronic Obstructive Pulmonary Disease: Lessons from the Important Treatment Trials

“…When prospectively tested in this subgroup of patients, the drug did prevent exacerbations 10 but only when this finding was confirmed in patients with very frequent exacerbations or a high risk of being hospitalised and who also took LABA/ICS and LAMA, was it possible to finally establish a treatment group where the intrusive side effects of treatment produced clinically important benefits 30,31 .…”

Roles of roflumilast, a selective phosphodiesterase 4 inhibitor, in airway diseases

“…Data from a series of 52-week-placebo trials of combined treatment with roflumilast and ICS-LABA or roflumilast and ICS-LABA-LAMA in severe COPD patients who experienced chronic bronchitis and frequent exacerbation were recently published. Adding roflumilast to ICS-LABA or ICS-LABA-LAMA resulted in a significant reduction of moderate to severe COPD exacerbation (58,59). In addition, the effect of roflumilast was more pronounced with increasing severity of exacerbation.…”