Two articles published in this week’s COPD special edition of The Lancet report that the drug roflumilast improves lung function and reduces exacerbations in patients with chronic obstructive pulmonary disease (COPD) who have chronic respiratory symptoms and are at greater risk of exacerbations. Roflumilast is an oral, once a day anti-inflammatory agent. The effect of this drug persists even when it is added to conventional treatment with inhaled long-acting bronchodilators. Therefore, roflumilast therapy could potentially become an essential treatment for these patients.
A key factor in the progress of COPD is chronic inflammation. Current treatment options avoid the clinical symptoms of COPD. But they have little effect on the underlying inflammatory processes linked with COPD. Furthermore, they do not stop the progression of the disease. Roflumilast belongs to a new class of anti-inflammatory drugs called phosphodiesterase 4 (PDE4) inhibitors. Earlier studies have proven that it can improve lung function and reduce the rate of exacerbations in some patients with moderate-to-severe COPD.
Leonardo Fabbri from the University of Modena and Reggio Emilia, Modena, Italy, and Klaus Rabe from Leiden University Medical Centre, Netherlands and colleagues set out to further investigate the potential of this new therapeutic strategy. They report the results of four randomised trials to examine the use of roflumilast in different subsets of patients with COPD.
Leonardo Fabbri and his team conducted two trials with identical design in two different populations. The results are reported in the first article. They investigated whether roflumilast would improve lung function and reduce the number of exacerbations requiring treatment with corticosteroids in patients with severe to very severe COPD who had symptoms of chronic bronchitis and a history of exacerbations. A total of 1,537 patients were randomly assigned to oral roflumilast and 1,554 to placebo, for a period of one year.
In general, roflumilast improved lung function and reduced the frequency of exacerbations. The effect persisted regardless of the patient’s smoking status and use of other medication, such as long-acting ß2 agonists. Lung function is determined by the forced expiratory volume (FEV) in one second and the greatest volume of air that can be breathed out in the first second of a large breath. It increased by 48mL in the roflumilast group compared with placebo. The rate of exacerbations that were moderate or severe per patient per year was 17 percent lower in the roflumilast treated group compared to the placebo group. On the other hand, adverse events were more frequent in patients treated with roflumilast (67 percent) than with placebo (62 percent).
The authors explain: “These results suggest that different subsets of patients exist within the broad range of COPD…and that targeted specific therapies could improve disease management.”
In the second article, Klaus Rabe and collaborators conducted two trials. They assessed whether roflumilast has a favourable effect when added to standard treatment with long-acting bronchodilators (ß2 agonist salmeterol and the inhaled antimuscarinic tiotropium). A total of 1,677 patients older than 40 years participated. They all had moderate-to-severe COPD and were randomly assigned to oral roflumilast or placebo once a day for 24 weeks in addition to salmeterol or tiotropium.
Results indicated that roflumilast added improvement in lung function in patients already receiving salmeterol or tiotropium. Roflumilast consistently improved the average FEV by 49mL in patients treated with salmeterol, and 80mL in patients given tiotropium, compared with placebo. Also, roflumilast improved respiratory symptoms. However, it was linked with more adverse events including nausea, diarrhoea, and weight loss.
In view of the findings, the authors suggest that roflumilast could turn into an essential treatment in patients with moderate-to-severe COPD who are already being treated with long-acting bronchodilators.
In an associated note, Paul O’Byrne and Gail Gauvreau from McMaster University Medical Center in Canada observe: “Reduction in mortality remains the holy grail in COPD therapy and the anti-inflammatory properties of phosphodiesterase-4 inhibitors, when added to conventional treatment, might further enhance this goal.”
“Roflumilast in symptomatic chronic obstructive pulmonary disease: two randomised clinical trials”
Peter M A Calverley, Klaus F Rabe, Udo-Michael Goehring, Søren Kristiansen, Leonardo M Fabbri, Fernando J Martinez, for the M2-124 and M2-125 study groups
Lancet 2009; 374: 685-94
The Lancet
Written by Stephanie Brunner (B.A.)