The trials – published in the same issue of The Lancet – involved more than 4500 patients in ten countries. Two of the trials examined the effects of roflumilast after 12 months, whilst each of the other two trials had a follow-up period of six months. All participants were aged over 40 years and each received either 500 micrograms of roflumilast per day, or placebo.
The 12-month trials enrolled a total of 3091 patients with severely reduced airflow, bronchitic symptoms and a history of exacerbations. Pooled data showed that prebronchodilator FEV1 (forced expiratory volume in one second) increased by 48ml in those who received roflumilast compared with those who were given placebo. Furthermore, patients in the roflumilast group experienced 17% fewer moderate or severe exacerbations than those in the placebo group.1
The shorter trials tested roflumilast in 1676 patients with moderate-to-severe COPD who had impaired lung function despite bronchodilatory treatment. Compared with placebo, roflumilast improved prebronchodilator FEV1 by an average of 49ml in individuals already receiving salmeterol. The improvement was even greater in patients receiving tiotropium-an average of 80ml.2
Adverse effects associated with roflumilast included nausea, diarrhoea and weight loss.
Roflumilast – currently under development by Nycomed – is a phosphodiesterase 4 enzyme inhibitor, targeting cells and mediators in the body believed to be important in the COPD disease process. If approved, roflumilast would be the first oral anti-inflammatory treatment for COPD.
"COPD can devastate people's lives and exacerbations can be extremely frightening, so a novel tablet like roflumilast is really exciting for those of us treating patients. Roflumilast acts differently to bronchodilators as it acts on the underlying condition, not primarily impacting on everyday symptoms," says Peter Calverley, Professor of Respiratory Medicine at the University of Liverpool, UK, lead author of two of the studies.
Nycomed submitted an application for approval to market roflumilast to the European Medicines Agency earlier this year.
NICE guidance on COPD
- Calverley PMA et al. Lancet 2009: 374; 685-94.
- Fabbri LM et al. Lancet 2009: 374; 695-703.