Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Meta-Analysis
. 2024 Oct;154(4):996-1007.
doi: 10.1016/j.jaci.2024.05.026. Epub 2024 Jun 7.

Leukotriene receptor antagonists as add-on therapy to antihistamines for urticaria: Systematic review and meta-analysis of randomized clinical trials

Daniel G Rayner  1 , Ming Liu  2 , Alexandro W L Chu  3 , Xiajing Chu  1 , Gordon H Guyatt  4 , Paul Oykhman  3 , Daniel J Cao  3 , Joseph Moellman  5 , Moshe Ben-Shoshan  6 , Diane R Baker  7 , Susan Waserman  3 , David Lang  8 , Javed Sheikh  9 , Sameer K Mathur  10 , Lisa A Beck  11 , David A Khan  12 , Eric T Oliver  13 , Rachel N Asiniwasis  14 , Emily F Cole  15 , Kathryn E Wheeler  16 , Lauren Runyon  12 , Jeffrey Chan  17 , Kathryn P Trayes  18 , Sanaz Eftekhari  19 , Donna D Gardner  20 , Tonya Winders  21 , Sarbjit S Saini  13 , Jonathan A Bernstein  22 , Derek K Chu  23
Affiliations
Free article
Meta-Analysis

Leukotriene receptor antagonists as add-on therapy to antihistamines for urticaria: Systematic review and meta-analysis of randomized clinical trials

Daniel G Rayner et al. J Allergy Clin Immunol. 2024 Oct.
Free article

Abstract

Background: The benefits and harms of adding antileukotrienes to H1 antihistamines (AHs) for the management of urticaria (hives, itch, and/or angioedema) remain unclear.

Objective: We sought to systematically synthesize the treatment outcomes of antileukotrienes in combination with AHs versus AHs alone for acute and chronic urticaria.

Methods: As part of updating American Academy of Allergy, Asthma & Immunology and American College of Allergy, Asthma, and Immunology Joint Task Force on Practice Parameters urticaria guidelines, we searched Medline, Embase, Central, LILACS, WPRIM, IBECS, ICTRP, CBM, CNKI, VIP, Wanfang, US Food and Drug Administration, and European Medicines Agency databases from inception to December 18, 2023, for randomized controlled trials (RCTs) evaluating antileukotrienes and AHs versus AHs alone in patients with urticaria. Paired reviewers independently screened citations, extracted data, and assessed risk of bias. Random effects models pooled effect estimates for urticaria activity, itch, wheal, sleep, quality of life, and harms. The GRADE approach informed certainty of evidence ratings. The study was registered at the Open Science Framework (osf.io/h2bfx/).

Results: Thirty-four RCTs enrolled 3324 children and adults. Compared to AHs alone, the combination of a leukotriene receptor antagonist with AHs probably modestly reduces urticaria activity (mean difference, -5.04; 95% confidence interval, -6.36 to -3.71; 7-day urticaria activity score) with moderate certainty. We made similar findings for itch and wheal severity as well as quality of life. Adverse events were probably not different between groups (moderate certainty); however, no RCT reported on neuropsychiatric adverse events.

Conclusion: Among patients with urticaria, adding leukotriene receptor antagonists to AHs probably modestly improves urticaria activity with little to no increase in overall adverse events. The added risk of neuropsychiatric adverse events in this population with leukotriene receptor antagonists is small and uncertain.

Keywords: Chronic urticaria (hives); leukotriene receptor antagonists; meta-analysis; montelukast; systematic review; zafirlukast.

PubMed Disclaimer

Conflict of interest statement

Disclosure statement This work was commissioned and funded by the American Academy of Allergy, Asthma & Immunology (AAAAI) and the American College of Allergy, Asthma & Immunology (ACAAI) through the Joint Task Force on Practice Parameters to inform upcoming guidance on the management of CU. The task force contributed to defining the scope of the review but otherwise had no role in study design, data collection, data analysis, or data interpretation. The funder received a copy of the report before submission. The review team had the ability, but not the obligation, to consider the funders’ feedback. Disclosure of potential conflict of interest: M. Ben-Shoshan reports consulting fees from Sanofi/Regeneron and Novartis. S. Waserman reports consulting fees from Medexus Pharmaceuticals and Miravo Healthcare. S. K. Mathur reports consulting fees from Novartis. E. T. Oliver reports consulting fees from Novartis and Sanofi/Regeneron. R. N. Asiniwasis reports payment or honoraria for lectures, presentations, speaker bureaus, manuscript writing, or educational events from Medexus Pharmaceuticals. S. Eftekhari is employed by the Asthma and Allergy Foundation of America, a nonprofit patient organization, which has received grants for patient education and unbranded initiatives from AstraZeneca, Bayer, Johnson & Johnson, Merck, and Sanofi/Regeneron. T. Winders reports payment or honoraria for lectures, presentations, speaker bureaus, manuscript writing, or educational events from AstraZeneca, GlaxoSmithKline, Merek, Novartis, and Sanofi/Regeneron. J. Bernstein reports consulting fees from AstraZeneca, Merck, Sanofi/Regeneron, and Pfizer; and leadership role in the AAAAI and the US Hereditary Angioedema Association. The rest of the authors declare that they have no relevant conflicts of interest.

MeSH terms

Substances