TY - JOUR T1 - Long-acting β2-agonist step-off in patients with controlled asthma: Systematic review with meta-analysis AU - Brozek JL, Kraft M, Krishnan JA, et al Y1 - 2012/10/08 N1 - 10.1001/archinternmed.2012.3250 JO - Archives of Internal Medicine SP - 1365 EP - 1375 VL - 172 IS - 18 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 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. SN - 0003-9926 M3 - doi: 10.1001/archinternmed.2012.3250 UR - http://dx.doi.org/10.1001/archinternmed.2012.3250 ER -