Study Identifies COPD Patient Subgroup Who Benefit Most From Roflumilast

Alison Rodriguez

A recent study aimed to identify the characteristics of patients who demonstrate the greatest risk reduction of exacerbations with roflumilast, which is used to treat chronic obstructive pulmonary disease (COPD). The study found that the medication is most successful in patients with prior hospitalization for exacerbation, greater exacerbation frequency, and higher baseline blood eosinophil count. 

The researchers analyzed data from the REACT and RE2SPOND studies in order to identify the rate of moderate or severe exacerbations per patient per year. Both studies were randomized, double-blind, placebo-controlled studies that evaluated the efficacy of roflumilast in treating COPD exacerbations.

In the overall intention-to-treat population (n = 4287), roflumilast reduced moderate or severe exacerbations by 12.3% (rate ratio, 0.88, 95% confidence interval, 0.80–0.97; P = .0086) and severe exacerbations by 16.1% (0.84; 0.71–0.99; P= .0409) versus placebo. The reduction in moderate or severe exacerbations with roflumilast was most pronounced in patients who had been hospitalized for an exacerbation in the prior year (0.74; 0.63–0.88; P= .0005); had more than 2 exacerbations in the prior year (0.79; 0.65–0.96; P = .0160); or had baseline eosinophils >150 cells/ml (0.81; 0.71–0.93; P = .0020), >150 to 300 cells/ml (0.84; 0.71–0.98; P= .0282), or >300 cells/ml (0.77; 0.61–0.97; P= .0264).

Similar subgroup results were noted for severe exacerbations. In patients with prior hospitalization and higher baseline blood eosinophil concentrations, roflumilast reduced moderate or severe exacerbations by 34.5% at >150 cells/ml (0.65; 0.52–0.82; P = 0.0003) and 42.7% at >300 cells/ml (0.57; 0.37–0.88; P= 0.0111) versus placebo.

The studies evaluated roflumilast when added to inhaled corticosteroid (ICS) plus a long-acting beta-agonist (LABA), with or without a long-acting muscarinic antagonist (LAMA), in patients with severe to very severe COPD with chronic bronchitis and a history of  or more exacerbations,” noted the authors. “These studies suggested that certain baseline variables may identify distinct COPD phenotypes that may derive greater benefit from roflumilast.”

Roflumilast reduced moderate to severe exacerbations by 12.3% and severe exacerbations by 16.1%, compared to placebo. The decrease in moderate or severe exacerbations was most prominent in patients who had previously been hospitalized for an exacerbation within the prior year, had more than 2 exacerbations within the prior year, or high eosinophils counts.

Many patients with COPD continue to suffer exacerbations and recurrent hospitalizations despite treatment with LAMA/LABA/ICS. Roflumilast is a selective phosphodiesterase-4 (PDE4) inhibitor recommended for maintenance treatment of COPD in patients with post-bronchodilator FEV1, 50% predicted, associated with chronic bronchitis and a history of exacerbations, as an add-on treatment.

“The results of this prespecified pooled analysis confirm the benefit of roflumilast in decreasing exacerbations, particularly in patients with prior hospitalizations and higher baseline blood eosinophil count,” concluded the researchers. “Clinical trials have shown that roflumilast as an add-on to dual or triple inhaled therapy leads to fewer exacerbations in patients with severe COPD associated with chronic bronchitis and frequent exacerbations. Because the systemic availability of roflumilast results in more side effects than inhaled treatments, it is important to better define the most responsive patient subgroup.”

The authors suggest that these results may help identify a subgroup of efficacy for roflumilast may contribute to a shift to more personalized therapy for patients with COPD.

Roflumilast is sold under the name Daliresp. It is not a bronchodilator and is not indicated for the relief of acute bronchospasm.

Martinez, FJ, Rabe, KF, Calverley PMA, et al. Determinants of response to roflumilast in severe chronic obstructive pulmonary disease. Am J Respir Crit Care Med. 2018;198(10):1268-1278. doi: 10.1164/rccm.201712-2493OC.
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