In Reply

The Pharmacological Treatment of Chronic Obstructive Pulmonary Disease by Prof. Dr. med. Adrian Gillissen, Prof. Dr. med. Peter Haidl, Prof. Dr. med. Martin Kohlhäufl, Prof. Dr. med. Dr. rer. nat. Klaus Kroegel, Dr. med. Thomas Voshaar, and PD Dr. med. Christian Gessner in issue 18/2016

The REACT study, which evaluated the efficacy of roflumilast given together with LABA and LAMA and had as its primary endpoint reduction of moderate and severe exacerbations of chronic obstructive pulmonary disease (COPD) per patient and year, yielded the following results (1):

In the intention to treat population the reduction in the COPD exacerbation rate versus placebo was 13.2% with Poisson regression analysis, corresponding to a risk rate reduction of 0.868 ([95% CI 0.753; 1.002], p = 0.0529), and 14.2% with binomial regression analysis, corresponding to a risk rate reduction of 0.858 ([0.740; 0.995], p = 0.0424). The analyses of the per-protocol population were even more favorable. Moreover, the rate of severe COPD exacerbations (secondary endpoint parameter) went down by more than 20% and lung function parameters improved. On the other hand, roflumilast did not change the CAT score. Adverse effects were reported in 67% of the roflumilast group and 59% of the placebo group. The most frequently occurring adverse effects were COPD exacerbations, diarrhea, and weight loss. The conflicts of interest were stated in the respective studies.

The number needed to treat (NNT) has been supplied in various publications on roflumilast (2, 3). In the study by Bateman et al., for example, the NNT to avoid one exacerbation per patient and year was 3.2 (3). The NNT in the REACT study is most likely higher because roflumilast was used in a cohort of COPD patients in whom other treatments had failed. The Global Initiative for Chronic Obstructive Lung Disease (GOLD) recommends the use of roflumilast as an additional measure to lower the elevated exacerbation rate in patients with chronic bronchitis and severe or extremely severe COPD whose disease was not sufficiently controlled by their previous medication (evidence recommendation grade B). Our review focused principally on the ICS evaluation of treatment for COPD, hence the reference to the GOLD recommendation with regard to roflumilast (1, 4).

DOI: 10.3238/arztebl.2016.0692b

Prof. Adrian Gillissen

Kreiskliniken Reutlingen

Conflict of interest statement

Prof. Gillissen has acted as a paid consultant for Chiesi, Teva, Elpen, and Berlin-Chemie. He has received reimbursement of congress attendance fees from Chiesi and Teva, and has had travel costs paid by Chiesi, Teva, Boehringer Ingelheim, Elpen, Almirall, and Berlin-Chemie. He has been paid for giving lectures by AstraZeneca, Elpen, Chiesi, Boehringer Ingelheim, and Berlin-Chemie.

References

1. Martinez FJ, Calverley PM, Goehring UM, Brose M, Fabbri LM, Rabe KF: Effect of roflumilast on exacerbations in patients with severe chronic obstructive pulmonary disease uncontrolled by combination therapy (REACT): a multicentre randomised controlled trial. Lancet 2015; 385: 857–66

2. Global Initiative for Chronic Obstructive Lung Disease: Global strategy for the diagnosis, management and prevention of COPD. Revised 2016; www.goldcopd.org (last accessed on 14 July 2016)

3. Bateman ED, Rabe KF, Calverley PM, et al.: Roflumilast with long-acting beta-2-agonists for COPD: influence of exacerbation history. Eur Respir J 2011; 38: 553–60

4. Gillissen A, Haidl P, Kohlhäufl M, Kroegel K, Voshaar T, Gessner C: The pharmacological treatment of chronic obstructive pulmonary disease. Dtsch Arztebl Int 2016; 113: 311–6