Long-Acting β 2 -Agonist Step-off in Patients With Controlled Asthma Systematic Review With Meta-analysis β 2 -Agonist Step-off in Controlled Asthma

Brozek JL, Kraft M, Krishnan JA, et al. — Mon, 08 Oct 2012 00:00:00 GMT

Background

Because of concerns about the safety of long-acting β₂-agonist (LABA) use in patients with asthma, withdrawal of the LABA is recommended by the US Food and Drug Administration once asthma is controlled by combination therapy with a LABA and inhaled corticosteroid (ICS).

Objective

To perform a systematic review and meta-analysis assessing evidence supporting the discontinuation of LABA therapy once asthma control has been achieved with a combination of ICS and LABA.

Data Sources

MEDLINE, EMBASE, and Cochrane Central Register of Controlled Trials databases were searched (through August 2010), references of identified studies and selected narrative review articles were evaluated, registries of clinical trials were reviewed, and manufacturers of LABAs were contacted.

Study Selection

Randomized controlled trials of discontinuation of LABA therapy in patients with asthma controlled with a combination of ICS and LABA.

Data Extraction

Two reviewers independently screened each title and abstract in the initial searches and then the full text of each nominated article to extract data for analyses.

Results

Of 1492 screened articles, only 5 trials involving patients aged 15 years or older fulfilled a priori–specified inclusion criteria. Results did not favor the LABA step-off approach compared with no change in treatment. The LABA step-off regimen increased asthma impairment, with worse Asthma Quality of Life Questionnaire score (mean difference [95% CI], 0.32 [0.14-0.51] points lower); worse Asthma Control Questionnaire score (0.24 [0.13-0.35] points higher); fewer symptom-free days (9.15% [1.62%-16.69%] less); and greater risk of withdrawal from study resulting from lack of efficacy or loss of asthma control (risk ratio, 3.27 [2.16-4.96]). Risk of exacerbations and deaths after LABA step-off were not evaluable because of the small number of events and short duration of follow-up.

Conclusions

Evidence suggests that discontinuing LABA therapy in adults and older children with asthma controlled with a combination of ICSs and LABAs results in increased asthma-associated impairment. Additional trials measuring all long-term patient-important outcomes are needed.

Black Clouds and Black Boxes Comment on “Long-Acting β 2 -Agonist Step-off in Patients With Controlled Asthma” Black Clouds and Black Boxes

Chan CM, Shorr AF. — Mon, 08 Oct 2012 00:00:00 GMT

For more than a decade, black clouds have surrounded the safety of long-acting β₂-agonists (LABAs) for asthma. Several studies indicate that these agents are associated with an increased risk for asthma-related morbidity and mortality. Although these trials were flawed and the absolute increase in mortality risk with LABAs was small, it persisted in multiple analyses. Thus, there is consensus that these agents have no role as monotherapy in asthma. Qualms remain, however, about their use in combination with inhaled corticosteroids (ICSs). Despite performing their own meta-analysis illustrating that coadministration of ICSs and LABAs essentially eliminated the enhanced risk related to LABA exposure, the US Food and Drug Administration (FDA) instituted a black box warning on LABAs. The warning states that LABAs, when given with ICSs, should be discontinued as soon as asthma control is achieved. The authors of the third Expert Panel Report of the National Asthma Education and Prevention Program guidelines interpreted the data differently and did not endorse such an approach. 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.

JAMA Internal Medicine: Asthma Topic Collection

Long-Acting β 2 -Agonist Step-off in Patients With Controlled Asthma Systematic Review With Meta-analysis β 2 -Agonist Step-off in Controlled Asthma

Black Clouds and Black Boxes Comment on “Long-Acting β 2 -Agonist Step-off in Patients With Controlled Asthma” Black Clouds and Black Boxes