NCBI Bookshelf. A service of the National Library of Medicine, National Institutes of Health.

  • This publication is provided for historical reference only and the information may be out of date.

This publication is provided for historical reference only and the information may be out of date.

Cover of Drug Class Review: Controller Medications for Asthma

Drug Class Review: Controller Medications for Asthma

Final Update 1 Report

Drug Class Reviews

, MD, MPH, , MPH, , PharmD, BCPS, , MSPH, , MS, , MPH, , MD, , MPH, and , PharmD, CDE, CPP.

Portland (OR): Oregon Health & Science University; .

Structured Abstract


To compare the efficacy and safety of inhaled corticosteroids (ICSs), long-acting beta-2 agonists (LABAs), leukotriene modifiers (LMs), anti-IgE therapy, combination products, and tiotropium for people with persistent asthma.

Data Sources:

To identify published studies, we searched MEDLINE, The Cochrane Library, Embase, International Pharmaceutical Abstracts, and reference lists of included studies through September 2010. We also requested dossiers of information from pharmaceutical manufacturers.

Review Methods:

Study selection, data abstraction, validity assessment, grading the strength of the evidence, and data synthesis were all carried out according to standard Drug Effectiveness Review Project methods.


Efficacy studies provide moderate strength of evidence (SOE) that equipotent doses of ICSs administered through comparable delivery devices do not differ in their ability to control asthma symptoms, prevent exacerbations, reduce the need for additional rescue medication, or in their overall incidence of adverse events or withdrawals due to adverse events. Evidence does not support a difference between montelukast and zafirlukast in their ability to decrease rescue medicine use or improve quality of life (low SOE for ≥ 12 years of age, insufficient <12), between formoterol and salmeterol in their ability to control symptoms, prevent exacerbations, improve quality of life, or cause harms among patients not controlled on ICSs alone (moderate SOE), or between budesonide/formoterol and fluticasone/salmeterol for efficacy or harms when each combination is administered via a single inhaler (moderate SOE for ≥ 12, insufficient <12). Meta-analyses and efficacy studies provide consistent evidence favoring omalizumab over placebo for most included outcomes. Omalizumab-treated patients have an increased incidence of injection site reactions and anaphylaxis compared to placebo-treated patients.

We found consistent evidence of greater benefit for subjects treated with ICS monotherapy compared with those treated with LM monotherapy (high SOE). Direct evidence suggests no difference in tolerability or overall adverse events between ICSs and LMs (moderate SOE). Specific adverse events reported with ICSs, such as cataracts and decreased growth velocity, were not found among patients taking LMs. The best longer-term evidence on growth (avg 4.3 years) for ICSs compared with placebo found that very small differences (1.1 cm) occurred primarily during the first year of treatment, suggesting that the effect on growth velocity occurs early in treatment and is not progressive. Evidence is insufficient to determine if long-term treatment with ICSs leads to a reduction in final adult height. Overall evidence indicates that ICSs and leukotriene receptor antagonists (LTRAs) are safer than LABAs for use as monotherapy (high SOE). Indirect evidence suggests that the potential increased risk of asthma-related death for those taking LABAs may be confined to patients not taking ICSs at baseline.

We did not find sufficient evidence to support the routine use of combination therapy rather than an ICS alone as first line therapy (moderate SOE for ≥ 12, insufficient <12). Results from large trials support greater efficacy with the addition of a LABA to an ICS than with a higher dose ICS (high SOE for ≥ 12, low <12) and greater efficacy with the addition of a LABA to an ICS over continuing the current dose of ICS alone for poorly controlled persistent asthma (high SOE). The addition of LMs to ICSs compared to continuing the same dose of ICSs resulted in improvement in rescue medicine use and no statistically significant differences in other health outcomes (low SOE for ≥ 12, insufficient <12). There is no apparent difference in symptoms, exacerbations, rescue medicine use, overall adverse events, or withdrawals due to adverse events between those treated with ICSs plus LTRAs compared to those treated with increasing the dose of ICSs (moderate SOE for ≥ 12, low <12). Results provide strong evidence that the addition of a LABA to ICS therapy (ICS+LABA) is more efficacious than the addition of an LTRA to ICS therapy (ICS+LTRA) (high SOE for ≥ 12, low <12). We found no difference in overall adverse events or withdrawals due to adverse events between ICS+LABA and ICS+LTRA (moderate SOE for ≥ 12, insufficient <12).


Overall findings do not suggest that one medication within any of the classes evaluated is significantly more effective or harmful than the other medications within the same class, with the exception of zileuton being more harmful than the other LMs. Our results support the general clinical practice of starting initial treatment for persistent asthma with an ICS. For people with poorly controlled persistent asthma taking an ICS, our findings suggest that the addition of a LABA is most likely to provide the greatest benefit as the next step in treatment.


Original Report: November 2008

The medical literature relating to this topic is scanned periodically. (See for description of scanning process). Prior versions of this report can be accessed at the DERP website.

Produced by RTI-UNC Evidence-based Practice Center. Cecil G. Sheps Center for Health Services Research, University of North Carolina at Chapel Hill, 725 Martin Luther King Jr. Blvd, CB# 7590, Chapel Hill, NC 27599-7590. Tim Carey, M.D., M.P.H., Director

Oregon Evidence-based Practice Center, Oregon Health & Science University, Mark Helfand, MD, MPH, Director

Acknowledgments: We extend our greatest appreciation to Katie Kiser, Pharm D., BCPS, Laura C. Morgan, MA, Patricia Thieda Keener, MA, and Daniel Reuland, MD, MPH for their expertise and contributions toward creating the original controller medications for asthma report. We also thank Irvin Mayers, MD, FRCPC, University of Alberta and Allan Luskin, MD, University of Wisconsin who served as clinical advisors and provided their thoughtful advice and input during the research process for the original report. Finally, we thank Claire Baker, Shannon Brode, Elizabeth Harden, and Megan Van Noord for their invaluable assistance with data abstraction, literature searches, and data entry.

Funding: The Drug Effectiveness Review Project, composed of 12 organizations including 11 state Medicaid agencies, and the Canadian Agency for Drugs and Technology in Health commissioned and funded for this report. These organizations selected the topic of the report and had input into its Key Questions. The content and conclusions of the report were entirely determined by the Evidence-based Practice Center researchers. The authors of this report have no financial interest in any company that makes or distributes the products reviewed in this report.

Suggested citation:

Jonas DE, Wines R, DelMonte M, Amick H, Wilkins T, Einerson B, Schuler CL, Wynia BA, Bryant Shilliday B. Drug class review: Controller medications for asthma. Final update 1 report.

The Agency for Healthcare Research and Quality has not yet seen or approved this report.

The purpose of this report is to make available information regarding the comparative effectiveness and safety profiles of different drugs within pharmaceutical classes. Reports are not usage guidelines, nor should they be read as an endorsement of, or recommendation for, any particular drug, use or approach. Oregon Health & Science University does not recommend or endorse any guideline or recommendation developed by users of these reports.

Copyright © 2011 by Oregon Health & Science University.
Bookshelf ID: NBK56695PMID: 22132427


Other titles in this collection

Related publications

Similar articles in PubMed

See reviews...See all...

Recent Activity

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

See more...