When used concomitantly with inhaled corticosteroids, roflumilast—the phosphodiesterase (PDE) 4 inhibitor currently under review by the US Food and Drug Administration—further improves lung function, reduces the rate of exacerbations, and has an additive therapeutic effect in patients with chronic obstructive pulmonary disease (COPD), said Stephen I. Rennard, MD, Professor of Internal Medicine, Division of Pulmonary, Critical Care, Sleep & Allergy, University of Nebraska, Omaha. He and his colleagues assessed data from 2 trials in the roflumilast development program that allowed for concurrent inhaled corticosteroid use.
Roflumilast Reduces Exacerbations
Of the 2686 patients enrolled in the 2 studies, roflumilast was used with inhaled corticosteroids in 1622 patients. Prebronchodilator forced expiratory volume in 1 second (FEV1) levels improved by 53 mL compared with placebo in the group receiving roflumilast plus inhaled corticosteroids, and by 49 mL compared with placebo in those not using inhaled corticosteroids.
Roflumilast was better at reducing exacerbations in patients who were also taking inhaled corticosteroids. The mean rate of COPD exacerbations was reduced by 19% with roflumilast compared with placebo with concomitant inhaled corticosteroid use, and by 8% without inhaled corticosteroids.
Dr Rennard said that concurrent treatment with inhaled corticosteroids identified patients who had more exacerbations and worse lung function at study entry. These patients also were more responsive to roflumilast, which suggests potential synergy of the 2 medication classes.
Useful Addition to COPD Armamentarium
A separate pooled analysis of 2 placebo-controlled clinical trials of roflumilast in 3091 patients with COPD demonstrated that roflumilast improved lung function in patients with or without use of an inhaled corticosteroid pretreatment, reported Andrew McIvor, MD, MSc, Firestone Institute for Respiratory Health at McMaster University, Canada.
“This analysis looked at patients who were pretreated with inhaled steroids,” he said. “Sometimes, when inhaled steroids are withdrawn, you see an increase in the exacerbation rate.”
Among the patients randomized to roflumilast who were pretreated with inhaled corticosteroids, prebronchodilator FEV1 increased by 37 mL over 52 weeks compared with a decline of 10 mL in the placebo groups.
Similar benefits with roflumilast treatment compared with placebo were observed in patients who were not treated with inhaled corticosteroids.
“I certainly feel that it [roflumilast] will be a very useful addition to the armamentarium of our patients. It’s very effective, and over 90% of patients have no problem with it. With PDE 4 inhibitors, some patients will get gastrointestinal intolerance, but there’s no need to monitor blood levels and there are no drug–drug interactions,” Dr McIvor said.
“Our study showed that roflumilast acted as an anti-inflammatory agent, perhaps with a different mode of action,” he continued. “I’m not saying that we’re going to stop Advair [fluticasone/ salmeterol] in our patients, but we might be able to reduce the dose from Advair 500/50 to Advair 100/50, and use roflumilast, because it’s tackling a different aspect. Patients are still having exacerbations with triple therapy, so roflumilast perhaps meets an unmet need.”