0
Correspondence |

ResponseResponse FREE TO VIEW

Jadwiga A. Wedzicha, MD; Klaus F. Rabe, MD; Fernando J. Martinez, MD; Dirk Bredenbröker, MD; Manja Brose, MS; Udo-Michael Goehring, MD; Peter M. A. Calverley, MD
Author and Funding Information

From the Centre of Respiratory Medicine (Dr Wedzicha), University College London, Royal Free Campus; Krakenhaus Grosshansdorf (Dr Rabe), Center for Pulmonology and Thoracic Surgery; Department of Internal Medicine (Dr Martinez), University of Michigan Medical Center; Department of Respiratory Medicine (Drs Bredenbröker and Goehring), Nycomed: a Takeda Company; Department of Analytical Science (Ms Brose), Takeda Pharmaceuticals International GmbH; and University of Liverpool (Dr Calverley).

Correspondence to: Jadwiga A. Wedzicha, MD, Centre for Respiratory Medicine, University College London, Royal Free Campus, London, NW3 2PF, England; e-mail: j.wedzicha@ucl.ac.uk


Financial/nonfinancial disclosures: The authors have reported to CHEST the following conflicts of interest: Dr Wedzicha has received honoraria for lectures and/or for serving on advisory boards from Nycomed: a Takeda Company, GlaxoSmithKline plc, Boehringer-Ingelheim GmbH, Pfizer Inc, Novartis AG, Bayer AG, Chiesi Ltd, Almirall, and Vectura Group plc and has obtained research grant funding for her department from Nycomed: a Takeda Company, GlaxoSmithKline plc, Chiesi Ltd, and Novartis AG. Dr Rabe has provided legal consultation services or expert witness testimony to AstraZeneca, Chiesi Ltd, Novartis AG, Merck Sharp & Dohme Corp, and GlaxoSmithKline plc. He has also received research funding from Altana Pharma AG, Novartis AG, AstraZeneca, Merck Sharp & Dohme Corp, and Nycomed: a Takeda Company. Drs Bredenbröker and Goehring and Ms Brose are employees of the study sponsor. Dr Martinez has participated on advisory boards in COPD development for Actelion Pharmaceuticals Ltd; Almirall; American Institutes for Research; AstraZeneca; Bayer AG; BoomCom, Inc; Forest Laboratories, Inc; GlaxoSmithKline plc; Ikaria; Janssen Pharmaceuticals, Inc; MedImmune; Merck; Novartis AG; Nycomed: a Takeda Company; Pearl Therapeutics; Pfizer Inc; and Bayer HealthCare (formerly Schering AG). He has been a member of the steering committee for COPD studies sponsored by GlaxoSmithKline plc; Forest Laboratories, Inc; MPex, Pharmaceuticals, Inc; and Nycomed: a Takeda Company. He has participated in Food and Drug Administration mock panels for Boehringer-Ingelheim GmbH and Forest Laboratories, Inc. The University of Michigan has received funds from Boehringer-Ingelheim GmbH for a COPD study. Dr Martinez has served on speakers’ bureaus or in continuing medical education activities sponsored by the American College of Chest Physicians; the American Lung Association; Almirall; AstraZeneca; William Beaumont Hospital; Boehringer-Ingelheim GmbH; the Center for Health Care Education; CME Incite; ePocrates; Forest Laboratories, Inc; the France Foundation; GlaxoSmithKline plc; Lovelace Foundation; MedEd; National Association for Continuing Education; Nycomed: a Takeda Company; Potomac Pharma Inc; Prescott Pharmaceuticals; Sanofi-Aventis; St. Luke’s Hospital; and UpToDate and has received royalties from Associates in Medical Marketing and Castle Connolly. Dr Calverley has served on the scientific advisory boards of AstraZeneca, Boehringer-Ingelheim GmbH, GlaxoSmithKline plc, Novartis AG, and Nycomed: a Takeda Company and has received research funding from AstraZeneca, Boehringer-Ingelheim GmbH, GlaxoSmithKline plc, and Nycomed: a Takeda Company.

Reproduction of this article is prohibited without written permission from the American College of Chest Physicians. See online for more details.


Chest. 2014;145(2):428. doi:10.1378/chest.13-2535
Text Size: A A A
Published online
To the Editor:

We would like to thank Dr Coyle for his interest in our recent article in CHEST.1 We apologize that the sentence included in the abstract, stating that the reduction in severe exacerbations leading to hospitalization/death was similar between subgroups, lacked clarity.

We presented pooled post hoc data on the effects of a 1-year treatment with roflumilast or placebo on exacerbation frequency in subsets of patients with either frequent (two or more) or infrequent (only one) exacerbations in the previous year (year 0). Among frequent exacerbators, roflumilast significantly lowered the risk for those remaining in the frequent exacerbator group by 20% compared with placebo (risk ratio [RR], 0.799; P = .0148). When looking at the proportion of patients with frequent severe exacerbations (two or more) at year 1 in the subgroup of frequent exacerbators, the risk reduction with roflumilast vs placebo was 46.6%; however, the effect missed statistical significance (RR, 0.534; 95% CI, 0.28-1.00; P = .0516). The wide CI is mainly attributable to the small subgroup experiencing severe COPD exacerbations, that is, 3.4% (roflumilast) and 6.5% (placebo) of the frequent exacerbator subgroup. Similarly, the 18% reduction of severe COPD exacerbations observed with roflumilast vs placebo in two 1-year studies failed to meet statistical significance (RR, 0.82; 95% CI, 0.63-1.06; P = .1334).2

Bateman et al3 investigated the effects of roflumilast on the number of hospitalizations resulting from severe COPD exacerbations based on data from the same two 1-year trials using negative binomial regression analysis. Because of the small number of severe COPD exacerbations (annual rate per patient, 0.16 and 0.126 for placebo and roflumilast, respectively), this statistical analysis is considered more appropriate than the Poisson regression model presented in the article by Calverley et al.2 Compared with placebo, roflumilast decreased the rate of hospitalizations resulting from severe COPD exacerbations by −21.6% (RR, 0.784; 95% CI, 0.619-0.993; P = .0439).

In conclusion, data suggest a consistent trend with borderline statistical significance in the reduction of severe COPD exacerbations with roflumilast vs placebo in patients with severe to very severe COPD. We express our sincerest respect to Dr Coyle for having initiated this discussion.

References

Wedzicha JA, Rabe KF, Martinez FJ, et al. Efficacy of roflumilast in the COPD frequent exacerbator phenotype. Chest. 2013;143(5):1302-1311. [CrossRef] [PubMed]
 
Calverley PM, Rabe KF, Goehring UM, Kristiansen S, Fabbri LM, Martinez FJ; M2-124 and M2-125 Study Groups. Roflumilast in symptomatic chronic obstructive pulmonary disease: two randomised clinical trials. Lancet. 2009;374(9691):685-694. [CrossRef] [PubMed]
 
Bateman ED, Jardim J, Goehring U-M, Brose M, Calverley PMA. Effect of roflumilast on hospitalizations in COPD patients. Eur Respir J. 2012;40(suppl 56):374s.
 

Figures

Tables

References

Wedzicha JA, Rabe KF, Martinez FJ, et al. Efficacy of roflumilast in the COPD frequent exacerbator phenotype. Chest. 2013;143(5):1302-1311. [CrossRef] [PubMed]
 
Calverley PM, Rabe KF, Goehring UM, Kristiansen S, Fabbri LM, Martinez FJ; M2-124 and M2-125 Study Groups. Roflumilast in symptomatic chronic obstructive pulmonary disease: two randomised clinical trials. Lancet. 2009;374(9691):685-694. [CrossRef] [PubMed]
 
Bateman ED, Jardim J, Goehring U-M, Brose M, Calverley PMA. Effect of roflumilast on hospitalizations in COPD patients. Eur Respir J. 2012;40(suppl 56):374s.
 
NOTE:
Citing articles are presented as examples only. In non-demo SCM6 implementation, integration with CrossRef’s "Cited By" API will populate this tab (http://www.crossref.org/citedby.html).

Some tools below are only available to our subscribers or users with an online account.

Related Content

Customize your page view by dragging & repositioning the boxes below.

  • CHEST Journal
    Print ISSN: 0012-3692
    Online ISSN: 1931-3543