Study Reviews Discontinuation of LABA Therapy in Patients with Asthma

CHICAGO – A review of five clinical trials suggests that discontinuing long-acting β2-agonist (LABA) therapy in adults and older children with asthma controlled with a combination of inhaled corticosteroids and LABAs may be associated with increased asthma-related impairment, according to a report published Online First by Archives of Internal Medicine, a JAMA Network publication.

The U.S. Food and Drug Administration has recommended that once asthma is controlled by a combination therapy of a LABA and inhaled corticosteroid (ICS) that LABA be withdrawn because of safety concerns, according to the study background.

Jan L. Brozek, M.D., Ph.D., ofMcMaster University,Ontario,Canada, and colleagues conducted a review and meta-analysis to assess the evidence supporting the discontinuation of LABAs once asthma control is achieved. The authors note a scarcity of studies evaluating the issue.

“The results of the available studies suggest that discontinuation of LABAs compared with continued use of LABAs and ICSs increases the risk of loss of asthma control in adults,” the authors comment. “However, there is uncertainty about estimated effects because of the risk of bias in the included studies, imprecision of the estimates and indirectness of the evidence.”

A LABA step-off regimen appeared to increase asthma impairment with worse Asthma Quality of Life Questionnaire score; worse Asthma Control Questionnaire score; and fewer symptom-free days, according to study results.

Researchers note there is an FDA mandate for LABA safety studies by manufacturers of these agents but the results of those studies will not be available for about five years.

“In the interim, the consistent trends that we identified for many asthma impairment factors, some of which were statistically significant, favor the continued use of LABAs. Thus, in contrast to FDA recommendations of stepping off LABA therapy when asthma is controlled, our analysis supports the continued use of LABAs to maintain asthma control,” the authors conclude. “Although our results indicate that LABA step-off will, on average, lead to worsening of asthma control, it is possible that step-off can be safe in a subset of patients.”

(Arch Intern Med. Published online August 27, 2012. doi:10.1001/archinternmed.2012.3250. Available pre-embargo to the media at http://media.jamanetwork.com.)

Editor’s Note: Authors and institutions made disclosures regarding grants, stock ownership, funding, staff support and consultation. Please see the article for additional information, including other authors, author contributions and affiliations, financial disclosures, funding and support, etc.

Commentary: Black Clouds and Black Boxes

In a commentary, Chee M. Chan, M.D., M.P.H., and Andrew F. Shorr, M.D., M.P.H., ofMedStar Washington Hospital Center,Washington, D.C., write: “With more than 25 million Americans having asthma, clinicians are left facing the quandary of how to manage these patients, many of whom receive suboptimal control with ICSs alone.”

“The history of LABAs serves as a case study for precisely how not to make public policy for complicated diseases. … The essential question remains: will regulatory authorities ever consider reevaluating their recommendations as the evidence evolves?” they continue.

‘We hope that this meta-analysis helps to lift some of the black clouds in the debate surrounding LABAs. Similarly, physicians must now reevaluate the contents of the black box for LABAs, particularly in individuals whose asthma is well controlled with combination LABA and ICS [inhaled corticosteroid] therapy,” they conclude.

(Arch Intern Med. Published online August 27, 2012. doi:10.1001/archinternmed.2012.3650. Available pre-embargo to the media at http://media.jamanetwork.com.)

Editor’s Note: Please see the article for additional information, including other authors, author contributions and affiliations, financial disclosures, funding and support, etc.

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For more information, contact JAMA Network Media Relations at 312-464-JAMA (5262) or email mediarelations@jamanetwork.org.
 

Media Advisory: To contact corresponding author Thomas B. Casale, M.D., call Deborah Daley at 402-280-1786 or email deborahdaley@creighton.edu. To contact corresponding commentary author Andrew F. Shorr, M.D., M.P.H., call So Young Pak at 202-877-2748 or email soyoung.pak@medstar.net.

Posted: August 2012

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