@article {Hatter00701-2020, author = {Lee Hatter and Pepa Bruce and Irene Braithwaite and Mark Holliday and James Fingleton and Mark Weatherall and Richard Beasley}, title = {ICS-formoterol reliever versus ICS and SABA reliever in asthma: a systematic review and meta-analysis}, elocation-id = {00701-2020}, year = {2020}, doi = {10.1183/23120541.00701-2020}, publisher = {European Respiratory Society}, abstract = {Background The Global Initiative for Asthma recommends as-needed inhaled corticosteroid (ICS)-formoterol as an alternative to maintenance ICS plus short-acting beta2-agonist (SABA) reliever at Step 2 of their stepwise treatment algorithm. Our aim was to assess the efficacy and safety of these two treatment regimens, with a focus on severe exacerbation prevention.Methods We performed a systematic review and meta-analysis of all randomised controlled trials (RCTs) comparing as-needed ICS-formoterol with maintenance ICS plus SABA. MEDLINE, EMBASE, the Cochrane Central Register of Controlled Trials, and ClinicalTrials.gov were searched from database inception to 12 December 2019. The primary outcome was time to first severe exacerbation. RCTs were excluded if they used as-needed budesonide-formoterol as part of a maintenance and reliever regimen, or did not report on severe exacerbations. The review is registered with PROSPERO (CRD42020154680).Results Four RCTs (n=8065 participants) were included in the analysis. As-needed ICS-formoterol was associated with a prolonged time to first severe exacerbation (hazard ratio 0.85, 95\%CI 0.73 to 1.00; p=0.048) and reduced daily ICS dose (mean difference -177.3 mcg, 95\%CI -182.2 to -172.4). Asthma symptom control was worse in the as-needed group (ACQ-5 mean difference 0.12, 95\%CI 0.09 to 0.14), though did not meet the minimal clinically important difference of 0.50 units. There was no significant difference in serious adverse events (odds ratio 1.07 95\%CI 0.84 to 1.36).Conclusion As-needed ICS-formoterol offers a therapeutic alternative to maintenance low-dose ICS plus SABA in asthma and may be the preferred option if severe exacerbation prevention is the primary aim of treatment.FootnotesThis manuscript has recently been accepted for publication in the ERJ Open Research. It is published here in its accepted form prior to copyediting and typesetting by our production team. After these production processes are complete and the authors have approved the resulting proofs, the article will move to the latest issue of the ERJOR online. Please open or download the PDF to view this article.Conflict of interest: Dr. Hatter has nothing to disclose.Conflict of interest: Dr. Bruce has nothing to disclose.Conflict of interest: Dr. Braithwaite reports personal fees from Equillium, outside the submitted work;.Conflict of interest: Dr. Holliday reports grants from AstraZeneca, grants from Health Research Council of New Zealand, outside the submitted work;.Conflict of interest: Dr. Fingleton reports grants, personal fees and non-financial support from AstraZeneca, grants from Genentech, grants, personal fees and non-financial support from GlaxoSmithKline, personal fees and non-financial support from Boheringer lngleheim, outside the submitted work;.Conflict of interest: Dr. Weatherall has nothing to disclose.Conflict of interest: Dr. Beasley reports grants and personal fees from AstraZeneca, grants from Genentech, grants from GlaxoSmithKline, personal fees from Theravance, from Avillion, outside the submitted work;. Dr. Beasley reports grants and personal fees from AstraZeneca, grants from Genentech, grants from GlaxoSmithKline, personal fees from Theravance, personal fees from Avillion, outside the submitted work;.}, URL = {https://openres.ersjournals.com/content/early/2020/10/22/23120541.00701-2020}, eprint = {https://openres.ersjournals.com/content/early/2020/10/22/23120541.00701-2020.full.pdf}, journal = {ERJ Open Research} }