1. Roflumilast in aggiunta ai corticosteroidi inalatori1

2. Gli studi M2-111 e M2-112 R VE Treatment 52 weeks Visit 0 Follow-up
Placebo o.d.
Roflumilast 500µg o.d.
Follow-up
30 days
Treatment
52 weeks R VE
Visit 0
Follow-up
Baseline
4 weeks
Placebo o.d.
Speaker notes
In a randomized, placebo-controlled, double-blind, parallel-group trial, 1513 patients with COPD (post-bronchodilator FEV1 ≤50% predicted; post-bronchodilator FEV1:FVC ratio ≤70%) were randomized to roflumilast or placebo once daily for 1 year.
In these studies, patients were allowed to continue treatment with inhaled corticosteroids (ICS, ≤2000µg beclomethasone dipropionate or equivalent) if taken on a regular basis at a constant daily dose for at least 3 months prior to study entry. About 60% of patients concomitantly received ICS during the studies.
References
Calverley PMA, Sanchez-Toril F, McIvor A, et al. Effect of 1-year treatment with roflumilast in severe chronic obstructive pulmonary disease. Am J Respir Crit Care Med 2007;176:154–161.
Rennard SI, Calverley PMA, Goehring, UM, et al. Exacerbation reduction by roflumilast – the importance of defining different subsets of patients with COPD.Respiratory Research 2011;12:18.
Allowed concomitant medication: ICSs (≤2000µg BDP or equivalent)
Approximately 60% of all patients were on ICS treatment
R = randomization
VE = Visit end
o.d. = once daily
ICS = Inhaled corticosteroids
BDP = Beclomethasone dipropionate
Calverley PMA, Sanchez-Toril F, McIvor A, et al. Am J Respir Crit Care Med 2007;176: 2 2

3. Studi M2-111 e M2-112: analisi del sottogruppo di pazienti trattati con ICS
Speaker notes
In the pooled analysis of M2-111 and M2-112, 1622 patients were taking concomitant Inhaled corticosteroids.
Patient baseline characteristics were similar in both groups.
The ICS-treated patients had slightly more severe COPD, indicated by lower lung function. This may be partially explained by the fact that concomitant ICS treatment selects for patients with a more advanced stage of the disease.
Reference
Rennard SI, Calverley PMA, Goehring, UM, et al. Exacerbation reduction by roflumilast – the importance of defining different subsets of patients with COPD. Respiratory Research 2011;12:18.
Data are expressed as mean (SD), unless otherwise stated
FEV1 = Forced expiratory volume in 1 second
FVC = Forced vital capacity
Rennard SI, Calverley PMA, Goehring UM, et al. Respiratory Research 2011; 12: 18. 3

4. Roflumilast e ICS: riduzione del tasso di riacutizzazioni
M2-111 and M2-112 pooled post hoc analysis
Speaker notes
In the pooled analysis of studies M2-111 and M2-112, roflumilast reduced the rate of moderate or severe exacerbations by 18.8% in patients with concomitant ICS.
This supports that the anti-inflammatory mechanism of roflumilast is different to that of ICS.
The trend for a higher benefit in patients on ICS may be partially explained by the fact that concomitant ICS treatment selects for patients with a more advanced stage of COPD. These patients are at a higher risk of exacerbation, indicated by the higher exacerbation rate in the placebo group in ICS-treated patients versus non ICS-treated patients (0.89 versus 0.46) and thus, treatment effects on exacerbations are easier to demonstrate in these patients.
Reference
Rennard SI, Calverley PMA, Goehring, UM, et al. Exacerbation reduction by roflumilast – the importance of defining different subsets of patients with COPD. Respiratory Research 2011;12:18.
ICS = Inhaled corticosteroids
Rennard SI, Calverley PMA, Goehring UM, et al. Respiratory Research 2011; 12: 18. 4

5. Roflumilast e ICS: maggiore riduzione delle riacutizzazioni nei pazienti con bronchite cronica
M2-111 and M2-112 pooled post hoc analysis of sub-group with chronic bronchitis +/- ICS
Speaker notes
In patients with severe COPD associated with chronic bronchitis, roflumilast reduced the rate of moderate or severe exacerbations compared with placebo in patients taking concomitant ICS by -30.2%
Reference
Rennard SI, Calverley PMA, Goehring, UM, et al. Exacerbation reduction by roflumilast – the importance of defining different subsets of patients with COPD. Respiratory Research 2011;12:18.
ICS = Inhaled corticosteroids
Rennard SI, Calverley PMA, Goehring UM, et al. Respiratory Research 2011; 12: 18. 5

6. Concetti chiave
Early clinical studies conducted in a broad patient population suggested clear potential for roflumilast as a treatment for COPD
Post hoc analyses indicated that the greatest benefits were seen in patients with severe COPD associated with chronic bronchitis
Pivotal phase III studies confirmed the efficacy of roflumilast in this patient population, demonstrating improved lung function and reduced exacerbation rate when added to maintenance therapy with bronchodilators or ICS 6