COPD is a leading cause of mortality in the US, and COPD exacerbations increase mortality risk, hospitalizations, and healthcare costs, accelerate disease progression, and decrease quality of life. Exacerbations increase in frequency with more severe COPD and a history of exacerbations predicts risk of future exacerbations. Therefore, in patients with severe COPD and a history of exacerbations, prescribing treatments at discharge to reduce exacerbation rates could be of great benefit. Roflumilast, an oral, oncedaily, selective phosphodiesterase4 inhibitor approved for patients with severe COPD associated with chronic bronchitis and a history of exacerbations, reduces the risk of experiencing COPD exacerbations. Here, data are presented from key trials evaluating the efficacy and safety of roflumilast 500mg (ROF) for COPD treatment.
Six phase 3 roflumilast trials (3 pairs of similar studies) evaluated exacerbation rates and lung function changes in COPD patients. M2111/112 were 1year trials in severetovery severe patients allowed concomitant ICS use. M2124/125 were 1year trials in severetovery severe patients with a history of exacerbations and chronic bronchitis allowing concomitant LABA use. Two 6month studies assessed moderatetosevere patients treated concomitantly with salmeterol (SAL; M2127) or tiotropium (TIO; M2128). A pool of 14 phase 23 trials (n=5766 ROF; n=5491 placebo [PBO]) evaluated adverse event (AE) frequency.
In M2111/112 (n=1327 ROF; n=1359 PBO), the moderate/severe exacerbation rate was 14.3% lower with roflumilast vs placebo (P=0.0257). Among a subset of patients with chronic bronchitis, the rate was 26.2% lower (P=0.0010) with roflumilast. In M2124/125 (n=1537 ROF; n=1554 PBO) the rate was 16.9% lower (P=0.0003) with roflumilast and the median time to first exacerbation was delayed by 67 days vs placebo (303 days ROF vs 236 days PBO; hazard ratio 0.886, P=0.0185). Among patients treated concomitantly with a LABA, the rate of exacerbations was reduced by 20.7% (P=0.0011) for roflumilast vs placebo. Prebronchodilator FEV1 increased with roflumilast over placebo by 51mL (P<0.0001) in M2111/112, 48mL (P<0.0001) in M2124/125, 49mL (P<0.0001) in M2127 (n=456 ROF+SAL; n=463 PBO+SAL), and 80mL (P<0.0001) in M2128 (n=365 ROF+TIO; n=364 PBO+TIO). The most commonly reported AEs with roflumilast (=2% and >placebo) were diarrhea, weight decrease, nausea, headache, back pain, influenza, insomnia, dizziness, and decreased appetite.
The safety and efficacy of roflumilast has been shown in a variety of COPD studies, and is independent of concomitant therapy with either ICS, LABAs, or LAMAs. Roflumilast is a beneficial treatment for patients with severe COPD taking concomitant COPD medications, as patients may experience fewer exacerbations.
To cite this abstract:Mosberg H, Dransfield M, Hanania N, Rowe P, Jennings P, Goehring U. An Evaluation of the Safety and Efficacy of Roflumilast for the Treatment of Chronic Obstructive Pulmonary Disease. Abstract published at Hospital Medicine 2012, April 1-4, San Diego, Calif. Abstract 97671. Journal of Hospital Medicine. 2012; 7 (suppl 2). https://www.shmabstracts.com/abstract/an-evaluation-of-the-safety-and-efficacy-of-roflumilast-for-the-treatment-of-chronic-obstructive-pulmonary-disease/. Accessed March 31, 2020.