Researchers at Sichuan University in China conducted a study to clarify the controversial therapeutic effects of roflumilast in patients with moderate-to-severe chronic obstructive pulmonary disease (COPD). The team found that roflumilast led to improved lung function and reduction of acute exacerbations and can be considered a valid alternative therapy in patients with COPD.
The research article, “Can roflumilast, a phosphodiesterase-4 inhibitor, improve clinical outcomes in patients with moderate-to-severe chronic obstructive pulmonary disease? A meta-analysis,” was published in the journal Respiratory Research.
Roflumilast is a novel selective inhibitor of phosphodiesterase-4 (PDE4), a vital enzyme in the metabolism of cyclic adenosine monophosphate (cAMP), and whose inhibition can inactivate immune and inflammatory cells. Combination treatment of a PDE4 inhibitor and a long-acting bronchodilator can be considered an alternative therapeutic approach in patients with severe COPD, according to recommendations by the Global Initiative for Chronic Obstructive Lung Disease (GLOD) guidelines.
However, different clinical trials reported conflicting results on the efficacy of roflumilast, and as a result, the accurate role of roflumilast in the treatment of patients with COPD remains controversial.
The research team analyzed all published randomized controlled trials assessing roflumilast that included clinical measurements, such as forced expiratory volume in one second (FEV1), forced vital capacity (FVC), transition dyspnea index (TDI), St George’s Respiratory Questionnaire (SGRQ), and the incidence of COPD exacerbations and adverse events to see whether roflumilast was effective and safe.
The clinical trial information was obtained through a computer search spanning the years 1946 through November 2015. Researchers used the databases Pubmed, Embase, Medline, Cochrane Central Register of Controlled Trials (CENTRAL), ISI Web of Science, and American College of Physician (ACP).
Results of the pooled analyses indicated that treatment with roflumilast resulted in significant improvements in pre- and post-bronchodilator FEV1, significant alleviation of dyspnea, and a decrease in acute exacerbations. However, researchers emphasized that roflumilast significantly increased the incidence of adverse events compared with a placebo.
“Roflumilast can be considered as an alternative therapy in selective patients with moderate-to-severe COPD due to the effect of lung function improvement, dyspnea alleviation, and acute exacerbation decrease, but increase of risk of adverse events. More large studies are needed, particularly with different follow-up and treatment duration, to further determine the role of roflumilast, including cost-effectiveness and time-to-survive, in patients with moderate-to-severe COPD,” the research team wrote in their article.