CHEST publication highlights efficacy of Daxas® (roflumilast) in the COPD frequent exacerbator phenotype

Treatment with roflumilast, an orally-administered highly selective phosphodiesterase 4 (PDE4) inhibitor, can help to shift chronic obstructive pulmonary disease (COPD) patients from the frequent to the more stable infrequent exacerbator state, according to a new data analysis published in CHEST.

The Global Initiative for Chronic Obstructive Lung Disease (GOLD) recently introduced a new system for assessing COPD, including exacerbation history as a key indicator of future risk. Patients who have a history of two or more exacerbations are classified as a high-risk subgroup, who require interventions with the potential of reducing exacerbation frequency.

Roflumilast is approved for severe COPD associated with chronic bronchitis and a history of frequent exacerbations. This post-hoc analysis pooled data from two one-year, placebo controlled, roflumilast (500 mcg once daily) studies in 3,091 symptomatic COPD patients with severe airflow obstruction.

The classification of exacerbator frequency status was based on definitions used in the Evaluation of COPD Longitudinally to Identify Predictive Surrogate Endpoints (ECLIPSE) study and the GOLD 2011 update.The ECLIPSE study showed that the majority of patients defined as frequent exacerbators at the start of the study remained in their respective phenotypic groups after one year of study, supporting the observation that this phenotype is relatively stable over time. Given the link between frequent exacerbations and increased inflammation, the authors hypothesised that the anti-inflammatory roflumilast would have a specific effect in patients with the frequent exacerbator phenotype.

The analysis showed that in frequent exacerbators  one year treatment with roflumilast reduced the risk of remaining a frequent exacerbator by 20% as compared to placebo (Risk ratio 0.799, p = 0.0148). In addition, one year treatment with roflumilast in infrequent exacerbators reduced the risk of becoming a frequent exacerbator by 23% (Risk ratio 0.768, p = 0.0018). This effect was independent of concomitant long-acting β2-agonists or previous inhaled corticosteroid treatment and was applicable for both moderate to severe exacerbations and severe exacerbations alone.

“The results of our analysis are important because for the first time they show that the anti-inflammatory effects of roflumilast in reducing exacerbations can have a stabilising effect on COPD, and this is clinically significant for both patients and clinicians,” commented lead study author Professor Jadwiga Wedzicha, Professor of Respiratory Medicine at University College London Medical School, London, UK. “Interventions that reduce exacerbation frequency, such as roflumilast, can contribute to ‘future risk reduction’ regardless of any effect they may or may not have on current symptoms.”

The frequent exacerbator phenotype has been proven to be associated with an accelerated decline in lung function, reduced physical activity, poorer quality of life and an increased risk of mortality. This makes the identification of patients at risk and the prevention of frequent exacerbations a logical focus for management strategies and research.

“Data such as these demonstrate the positive effects pharmacological interventions, like roflumilast, can have on the exacerbation frequency status in this high-risk subgroup of patients,” commented Ulrich Thienel, Vice President and Therapeutic Area Leader Immunology and Respiratory, Takeda.


Wedzicha, J.A. et al. (2012) Efficacy Of Roflumilast In The Chronic Obstructive Pulmonary Disease Frequent Exacerbator Phenotype. CHEST.doi:10.1378/chest.12–148

Global Strategy for the Diagnosis, Management and Prevention of COPD, Global Initiative for Chronic Obstructive Lung Disease (GOLD) 2011.

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