0
Correspondence |

ResponseResponse FREE TO VIEW

Jason Rho, MD; Nancy Ho, MD; Vinay Prasad, MD
Author and Funding Information

From the Division of Pulmonology and Critical Care (Dr Rho), Department of Medicine, University of Texas Southwestern; and National Institute of Diabetes and Digestive and Kidney Diseases (Dr Ho) and Medical Oncology Branch (Dr Prasad), National Cancer Institute, National Institutes of Health.

CORRESPONDENCE TO: Vinay Prasad, MD, Medical Oncology Branch, National Cancer Institute, National Institutes of Health, 10 Center Dr, 10/12N226, Bethesda, MD 20892; e-mail: vinayak.prasad@nih.gov


FINANCIAL/NONFINANCIAL DISCLOSURES: The authors have reported to CHEST that no potential conflicts of interest exist with any companies/organizations whose products or services may be discussed in this article.

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


Chest. 2015;148(1):e31-e32. doi:10.1378/chest.15-0837
Text Size: A A A
Published online
To the Editor:

We thank Dr Worndl and colleagues for their letter in response to our article,1 which argued that industry-sponsored trials for roflumilast had been inadequately designed to best answer patient-centered questions as part of a Point and Counterpoint editorial debate.1,2 Dr Worndl and colleagues raise an important point: The real-world side effects of roflumilast far exceed those seen in pivotal randomized trials. In their own analysis, they note that 84% of patients with moderate to severe COPD discontinued the drug. This number far exceeds the percentages quoted in randomized trials.

Other independent groups have noted similar inflated real-world rates of roflumilast discontinuation. A retrospective analysis of two hospitals in Barcelona, Spain, found that among 55 consecutive patients prescribed roflumilast according to local guidelines, 11 patients (20%) discontinued the drug within 12 weeks of starting it, and another 16 patients (29%) discontinued between 12 and 52 weeks.3 Altogether, just less than one-half of participants took the drug for < 1 year. Sixty-nine percent of participants experienced side effects in this study, with nausea, diarrhea, and weight loss commonly reported. Weight loss was greater in those who withdrew from treatment than in those who remained on therapy.

In a recent randomized study of roflumilast, the sponsor stopped providing participants with the drug at the end of 52 weeks, although the drug remained available commercially. Interestingly, only 6% and 7% of patients assigned to roflumilast or placebo, respectively, opted to take the medication in the poststudy period.4

Finally, others have noted that there are several discrepancies between the reporting of events in publications of pivotal trials and those that appear in the US Food and Drug Administration’s independent tallying of the same safety data.5 For instance, trial publications do not make it clear that 12 cases of diarrhea among users of roflumilast were so intractable that they required hospitalization.6 Moreover, rates of psychiatric disturbances, such as increased suicidality, were noted solely by the Food and Drug Administration. In a more recent randomized trial of roflumilast, a history of depression with suicidal ideation or behavior is listed as exclusion criteria.4

Although larger studies are needed to provide better estimates of the real-world tolerability of roflumilast, thus far, the preliminary evidence appears unfavorable and is a marked departure from the randomized trials submitted for the drug’s approval. Ironically, it may be these smaller, nonindustry-sponsored studies that shed further light onto the true impact of the severity of the side effects of roflumilast.

References

Rho J, Ho N, Prasad V. Counterpoint: were industry-sponsored roflumilast trials appropriate? No. Chest. 2014;145(5):939-942. [CrossRef] [PubMed]
 
Suissa S, Rabe KF. Point: were industry-sponsored roflumilast trials appropriate? Yes. Chest. 2014;145(5):937-939. [CrossRef] [PubMed]
 
Muñoz-Esquerre M, Diez-Ferrer M, Montón C, et al. Roflumilast added to triple therapy in patients with severe COPD: a real life study. Pulm Pharmacol Ther. 2015;30:16-21. [CrossRef] [PubMed]
 
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(9971):857-866. [CrossRef] [PubMed]
 
Gupta S. Side-effects of roflumilast. Lancet. 2012;379(9817):710-711. [CrossRef] [PubMed]
 
Center for Drug Evaluation and Research. Application number 022522Orig1s000: medical review(s). Food and Drug Administration website. http://www.accessdata.fda.gov/drugsatfda_docs/nda/2011/022522Orig1s000MedR.pdf. Accessed April 4, 2015.
 

Figures

Tables

References

Rho J, Ho N, Prasad V. Counterpoint: were industry-sponsored roflumilast trials appropriate? No. Chest. 2014;145(5):939-942. [CrossRef] [PubMed]
 
Suissa S, Rabe KF. Point: were industry-sponsored roflumilast trials appropriate? Yes. Chest. 2014;145(5):937-939. [CrossRef] [PubMed]
 
Muñoz-Esquerre M, Diez-Ferrer M, Montón C, et al. Roflumilast added to triple therapy in patients with severe COPD: a real life study. Pulm Pharmacol Ther. 2015;30:16-21. [CrossRef] [PubMed]
 
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(9971):857-866. [CrossRef] [PubMed]
 
Gupta S. Side-effects of roflumilast. Lancet. 2012;379(9817):710-711. [CrossRef] [PubMed]
 
Center for Drug Evaluation and Research. Application number 022522Orig1s000: medical review(s). Food and Drug Administration website. http://www.accessdata.fda.gov/drugsatfda_docs/nda/2011/022522Orig1s000MedR.pdf. Accessed April 4, 2015.
 
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.

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