Michael Miligkos, MD, MS; Raveendhara R. Bannuru, MD, PhD; Hadeel Alkofide, MS, PhD; Sucharita R. Kher, MD; Christopher H. Schmid, PhD (*); Ethan M. Balk, MD, MPH (*)
Disclaimer: The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.
Grant Support: By the National Center for Research Resources Award (UL1RR025752) and the National Center for Advancing Translational Sciences, National Institutes of Health (UL1TR000073 and UL1TR001064).
Disclosures: Dr. Bannuru reports grants from the Agency for Healthcare Research and Quality outside the submitted work. Authors not named here have disclosed no conflicts of interest. Forms can be viewed at www.acponline.org/authors/icmje/ConflictOfInterestForms.do?msNum=M15-1059.
Editors' Disclosures: Christine Laine, MD, MPH, Editor in Chief, reports that she has no financial relationships or interests to disclose. Darren B. Taichman, MD, PhD, Executive Deputy Editor, reports that he has no financial relationships or interests to disclose. Cynthia D. Mulrow, MD, MSc, Senior Deputy Editor, reports that she has no relationships or interests to disclose. Deborah Cotton, MD, MPH, Deputy Editor, reports that she has no financial relationships or interest to disclose. Jaya K. Rao, MD, MHS, Deputy Editor, reports that she has stock holdings/options in Eli Lilly and Pfizer. Sankey V. Williams, MD, Deputy Editor, reports that he has no financial relationships or interests to disclose. Catharine B. Stack, PhD, MS, Deputy Editor for Statistics, reports that she has stock holdings in Pfizer.
Reproducible Research Statement:Study protocol, statistical code, and data set: Available from Dr. Miligkos (e-mail, email@example.com).
Requests for Single Reprints: Michael Miligkos, MD, MS, Laboratory of Biomathematics, University of Thessaly School of Medicine, 22 Papakyriazi Street, 41222, Larissa, Greece; e-mail, firstname.lastname@example.org.
Current Author Addresses: Dr. Miligkos: Laboratory of Biomathematics, University of Thessaly School of Medicine, 22 Papakyriazi Street, 41222, Larissa, Greece.
Dr. Bannuru: Center for Treatment Comparison and Integrative Analysis (CTCIA), Tufts Medical Center, 800 Washington Street, Boston, MA 02111.
Dr. Alkofide: Sackler School of Biomedical Sciences, Tufts University, 35 Kneeland Street, Boston, MA 02111.
Dr. Kher: Division of Pulmonary, Critical Care and Sleep Medicine, 800 Washington Street, Boston, MA 02111.
Drs. Schmid and Balk: Center for Evidence Based Medicine, Brown University School of Public Health, Box G-S121-8, Providence, RI 02912.
Author Contributions: Conception and design: M. Miligkos, R.R. Bannuru, H. Alkofide, S.R. Kher, C.H. Schmid, E.M. Balk.
Analysis and interpretation of the data: M. Miligkos, R.R. Bannuru, H. Alkofide, C.H. Schmid, E.M. Balk.
Drafting of the article: M. Miligkos, R.R. Bannuru, H. Alkofide.
Critical revision of the article for important intellectual content: M. Miligkos, R.R. Bannuru, H. Alkofide, C.H. Schmid, E.M. Balk.
Final approval of the article: M. Miligkos, R.R. Bannuru, H. Alkofide, S.R. Kher, C.H. Schmid, E.M. Balk.
Provision of study materials or patients: M. Miligkos, R.R. Bannuru.
Statistical expertise: M. Miligkos, R.R. Bannuru, H. Alkofide, C.H. Schmid, E.M. Balk.
Collection and assembly of data: M. Miligkos, R.R. Bannuru, H. Alkofide.
Leukotriene-receptor antagonists (LTRAs) are recommended as an alternative treatment in patients with mild asthma, but their effect compared with placebo is unclear.
To determine the benefits and harms of LTRAs as monotherapy or in combination with inhaled corticosteroids compared with placebo in adults and adolescents with asthma.
MEDLINE and the Cochrane Central Register of Controlled Trials from inception through June 2015.
Peer-reviewed, English-language, randomized, controlled trials in patients with asthma that reported the effect of LTRAs versus placebo on measures of asthma control.
Three researchers extracted data on study population, interventions, outcome measures, and adverse events. One researcher assessed risk of bias.
Of the 2008 abstracts that were screened, 50 trials met eligibility criteria. Random-effects meta-analyses of 6 trials of LTRA monotherapy showed that LTRAs reduced the risk for an exacerbation (summary risk ratio [RR], 0.60 [95% CI, 0.44 to 0.81]). In 4 trials of LTRAs as add-on therapy to inhaled corticosteroids, the summary RR for exacerbation was 0.80 (CI, 0.60 to 1.07). Leukotriene-receptor antagonists either as monotherapy or as add-on therapy to inhaled corticosteroids increased FEV1, whereas FEV1 percentage of predicted values was improved only in trials of LTRA monotherapy. Adverse event rates were similar in the intervention and comparator groups.
Variation in definitions and reporting of outcomes, high risk of bias in some studies, heterogeneity of findings, possible selective outcome reporting bias, and inability to assess the effect of asthma severity on summary estimates.
Leukotriene-receptor antagonists as monotherapy improved asthma control compared with placebo, but which patients are most likely to respond to treatment with LTRAs remains unclear.
National Institutes of Health.
Michael Miligkos, Raveendhara R. Bannuru, Hadeel Alkofide, Sucharita R. Kher, Christopher H. Schmid, Ethan M. Balk. Leukotriene-Receptor Antagonists Versus Placebo in the Treatment of Asthma in Adults and Adolescents: A Systematic Review and Meta-analysis. Ann Intern Med. 2015;163:756–767. doi: 10.7326/M15-1059
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Published: Ann Intern Med. 2015;163(10):756-767.
Published at www.annals.org on 22 September 2015
Asthma, Healthcare Delivery and Policy, Pulmonary/Critical Care.
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Print ISSN: 0003-4819 | Online ISSN: 1539-3704
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