Long-acting β2-agonist step-off in patients with controlled asthma: Systematic review with meta-analysis

Jan L. Brozek, Monica Kraft, Jerry A. Krishnan, Michelle M. Cloutier, Stephen C. Lazarus, James T. Li, Nancy Santesso, Robert C. Strunk, Thomas B. Casale

Research output: Contribution to journalReview article

55 Citations (Scopus)

Abstract

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 articleswere 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.

Original languageEnglish (US)
Pages (from-to)1365-1375
Number of pages11
JournalArchives of internal medicine
Volume172
Issue number18
DOIs
StatePublished - Oct 8 2012
Externally publishedYes

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Meta-Analysis
Asthma
Adrenal Cortex Hormones
Therapeutics
Information Storage and Retrieval
United States Food and Drug Administration
MEDLINE
Registries
Randomized Controlled Trials
Odds Ratio
Quality of Life
Clinical Trials
Databases
Safety

ASJC Scopus subject areas

  • Internal Medicine

Cite this

Long-acting β2-agonist step-off in patients with controlled asthma : Systematic review with meta-analysis. / Brozek, Jan L.; Kraft, Monica; Krishnan, Jerry A.; Cloutier, Michelle M.; Lazarus, Stephen C.; Li, James T.; Santesso, Nancy; Strunk, Robert C.; Casale, Thomas B.

In: Archives of internal medicine, Vol. 172, No. 18, 08.10.2012, p. 1365-1375.

Research output: Contribution to journalReview article

Brozek, JL, Kraft, M, Krishnan, JA, Cloutier, MM, Lazarus, SC, Li, JT, Santesso, N, Strunk, RC & Casale, TB 2012, 'Long-acting β2-agonist step-off in patients with controlled asthma: Systematic review with meta-analysis', Archives of internal medicine, vol. 172, no. 18, pp. 1365-1375. https://doi.org/10.1001/archinternmed.2012.3250
Brozek, Jan L. ; Kraft, Monica ; Krishnan, Jerry A. ; Cloutier, Michelle M. ; Lazarus, Stephen C. ; Li, James T. ; Santesso, Nancy ; Strunk, Robert C. ; Casale, Thomas B. / Long-acting β2-agonist step-off in patients with controlled asthma : Systematic review with meta-analysis. In: Archives of internal medicine. 2012 ; Vol. 172, No. 18. pp. 1365-1375.
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abstract = "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 articleswere 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.",
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AU - Krishnan, Jerry A.

AU - Cloutier, Michelle M.

AU - Lazarus, Stephen C.

AU - Li, James T.

AU - Santesso, Nancy

AU - Strunk, Robert C.

AU - Casale, Thomas B.

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N2 - 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 articleswere 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.

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