Roflumilast, an oral, once a day anti-inflammatory agent, 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. The effect persists even when roflumilast is added to conventional treatment with inhaled long-acting bronchodilators. Thus, roflumilast therapy has the potential to become an important treatment for these patients. These are the conclusions of two Articles published in this week's COPD special edition of the Lancet.
Chronic inflammation is a key factor in the development of COPD. However, current treatment options which prevent the clinical symptoms of COPD have little effect on the underlying inflammatory processes associated with COPD, and do not reduce the progression of the disease. Previous studies have shown that roflumilast—one of a new class of anti-inflammatory drugs called phosphodiesterase 4 (PDE4) inhibitors—can improve lung function and reduce the rate of exacerbations in some patients with moderate-to-severe COPD.
To further investigate the potential of this new therapeutic strategy, Leonardo Fabbri from the University of Modena and Reggio Emilia, Modena, Italy, and Klaus Rabe from Leiden University Medical Centre, Netherlands and colleagues report the results of four randomised trials to examine the use of roflumilast in different subsets of patients with COPD.
In the first Article, Leonardo Fabbri and colleagues conducted two trials with identical design in two different populations to investigate 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. Patients were randomly assigned to oral roflumilast (1537) or placebo (1554) for 1 year.
Overall, roflumilast improved lung function and reduced the frequency of exacerbations regardless of the patient's smoking status and use of other medication, such as long-acting ß2 agonists. Lung function (determined by FEV1*) 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% lower in the roflumilast treated group compared to those given placebo. However, adverse events were more common in patients treated with roflumilast (67%) than with placebo (62%).
The authors say: "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 colleagues conducted two trials to examine whether roflumilast has a beneficial effect when added to standard treatment with long-acting bronchodilators (ß2 agonist salmeterol and the inhaled antimuscarinic tiotropium). In total, 1677 patients older than 40 years with moderate-to-severe COPD were randomly assigned to oral roflumilast or placebo once a day for 24 weeks in addition to salmeterol or tiotropium.
Findings showed that roflumilast further improved lung function in patients already receiving salmeterol or tiotropium. Compared with placebo, roflumilast consistently improved mean FEV1 by 49mL in patients treated with salmeterol, and 80mL in patients given tiotropium. In addition, roflumilast improved respiratory symptoms, but was also associated with more adverse events including nausea, diarrhoea, and weight loss.
The authors suggest that roflumilast could become an important treatment in patients with moderate-to-severe COPD who are already being treated with long-acting bronchodilators.
In an accompanying Comment, Paul O'Byrne and Gail Gauvreau from McMaster University Medical Center in Canada say: "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."
Professor Leonardo Fabbri, University of Modena and Reggio Emilia, Modena, Italy T) +39 3482945522 / +39 (0)59 4222 198 E) Leonardo.fabbri@unimore.it
Professor Klaus Rabe, Leiden University Medical Centre, Leiden, Netherlands. T) +31 (0)71 526 2950 E) k.f.rabe@lumc.nl
Dr Paul O'Byrne, McMaster University Medical Center, Ontario, Canada.T) +1 9055 212 100 Ext. 76373 E) obyrnep@mcmaster.ca
For full Article and Comment, see: http://press.thelancet.com/copdrof.pdf
Notes to editors: *FEV1 = the forced expiratory volume in one second, which is the greatest volume of air that can be breathed out in the first second of a large breath.
Journal
The Lancet