ROFLUMILAST (DALIRESP®)















REACT trial - Roflumilast vs Placebo in Severe COPD, Lancet (2013) [PubMed abstract]
  • The REACT trial enrolled 1945 patients with severe COPD
Main inclusion criteria
  • Smoking history at least 20 pack-year
  • Diagnosis of COPD
  • FEV1/FVC ratio < 0.70
  • FEV1 ≤ 50% of predicted
  • History of ≥ 2 exacerbations in the previous year
  • Using ICS + LABA for 12 months prior to enrollment
Main exclusion criteria
  • Diagnosis of asthma or other major lung disease
Baseline characteristics
  • Average age 65 years
  • Using long-acting muscarinic antagonist - 70%
  • Average postbronchodilator FEV1/FVC - 40%
  • Current smoker - 43%
Randomized treatment groups
  • Group 1 (969 patients) - Roflumilast 500 mcg once daily
  • Group 2 (966 patients) - Placebo once daily
  • All patients continued with ICS + LABA therapy. Patients already taking a LAMA (70%) were allowed to continue it.
  • If a patient had an exacerbation that needed additional treatment during the study, the investigator could give them up to 40 mg prednisolone, administered systemically, per day for 7 – 14 days
  • The following treatments were not allowed: oral and parenteral glucocorticosteroids (except to treat acute exacerbations); long-acting beta agonist or inhaled corticosteroid monotherapy; short-acting muscarinic antagonists; any short-acting beta agonists (with the exception of salbutamol) or oral beta agonists
Primary outcome: Rate of moderate-to-severe COPD exacerbations per patient per year. Moderate exacerbations were defined as those that needed treatment with oral or parenteral glucocorticosteroids (with or without antibiotics), and severe exacerbations were defined as those that needed hospital admission, led to death, or both. Patients were treated and followed-up for one year.
Results

Duration: 1 year
Outcome Roflumilast Placebo Comparisons
Primary outcome (events/patient/year) 0.805 0.927 RR 0.87, 95%CI [0.753 - 1.002], p=0.0529
Median time to first exacerbation 103.5 days 111.5 days HR 0.92, 95%CI [0.800 - 1.054], p=0.22
Change in postbronchodilator FEV1 +52 ml -4 ml p<0.0001
Discontinuation due to adverse event 11% 5% N/A
Diarrhea 10% 4% N/A
Weight loss 9% 3% N/A
Nausea 6% 2% N/A

Findings: Our findings suggest that roflumilast reduces exacerbations and hospital admissions in patients with severe chronic obstructive pulmonary disease and chronic bronchitis who are at risk of frequent and severe exacerbations despite inhaled corticosteroid and long-acting β2 agonist therapy, even in combination with tiotropium.




  • Reference: Manufacturer's PI
Side effect Roflumilast 500 mcg once daily
(N=4438)		 Placebo once daily
(N=4192)
Diarrhea 9.5% 2.7%
Weight decrease 7.5% 2.1%
Nausea 4.7% 1.4%
Headache 4.4% 2.1%
Back pain 3.2% 2.2%
Influenza 2.8% 2.7%
Insomnia 2.4% 1.0%
Dizziness 2.1% 1.1%
Decreased appetite 2.1% 0.4%