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Does Roflumilast Reduce COPD Exacerbations?

Am J Respir Crit Care Med; 2016 Sep 1; Martinez, et al

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While roflumilast failed to statistically reduce moderate and/or severe exacerbations in the overall population, it did improve lung function and reduced exacerbations in individuals with frequent exacerbations and/or hospitalization history, a recent study found. In this 52-week, phase 4, double-blind, controlled RE(2)SPOND trial, participants aged ≥40 years with severe/very severe COPD , chronic bronchitis, 2 or more exacerbations and/or hospitalizations in the previous year, and receiving inhaled corticosteroid/long-acting β2-agonist with or without LAMA daily for 3 or more months were equally randomized to once-daily roflumilast, 500 μg (n=1,178), or placebo (n=1,176). Researchers found:

• Rate of moderate or severe exacerbations per patient year was reduced by 8.5% with roflumilast vs placebo; however, the between-group difference was not statistically significant.

• Conversely, roflumilast improved lung function, and significantly reduced the rate of moderate or severe exacerbations in participants with a history of >3 exacerbations and/or ≥1 hospitalizations in the prior year.

• Adverse event-related discontinuations occurred in 11.7% roflumilast-treated and 5.4% placebo-treated participants.

• Deaths occurred in 2.5% roflumilast vs 2.1% placebo participants.

Citation: Martinez FJ, Rabe KF, Sethi S, et al. Effect of roflumilast and inhaled corticosteroid/long-acting β2-agonist on chronic obstructive pulmonary disease exacerbations (RE(2)SPOND). A randomized clinical trial. Am J Respir Crit Care Med. 2016;194(5):559-67. doi:10.1164/rccm.201607-1349OC.

Commentary: Roflumilast (Daliresp) is a selective PDE-4 inhibitor, given as a single 500 mg tablet daily, which is FDA approved to decrease the rate of exacerbations in patients with severe COPD associated with chronic bronchitis and a history of exacerbation.1 Entry to the registration trials required an FEV1 ≤50% predicted and looked at exacerbations as an endpoint. In those trials, patients with COPD and chronic bronchitis who had an exacerbation in the last year had a significant reduction in the rate of moderate or severe exacerbations compared to placebo. In the RE(2)SPOND trial reviewed here, the effect of roflumilast on exacerbations did not reach statistical significance. It did, however, show a significant reduction in moderate or severe exacerbations in the more severe subgroup who had a history of >3 exacerbations and/or ≥1 hospitalizations in the prior year, suggesting that roflumilast may have its most important place in the treatment of patients with severe COPD and chronic bronchitis who have frequent exacerbations. —Neil Skolnik, MD

1. Daliresp [package insert]. Wilmington, DE: AstraZeneca Pharmaceuticals, 2016. http://www.azpicentral.com/daliresp/pi_daliresp.pdf#page=1. Accessed October 17, 2016.

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