Combination treatment with omalizumab and rush immunotherapy for ragweed-induced allergic rhinitis: Inhibition of IgE-facilitated allergen binding
Open accessAbstract
Background The combination of anti-IgE (omalizumab) therapy with ragweed injection immunotherapy for seasonal allergic rhinitis results in a significant reduction in systemic side effects and enhanced efficacy compared with immunotherapy alone. One proposed mechanism of immunotherapy is to induce regulatory antibodies that inhibit facilitated antigen presentation.Objectives We sought to determine whether the combination protocol has a cumulative effect on inhibition of facilitated antigen presentation both during and after discontinuation of treatment.Methods Ragweed allergen immunotherapy with and without omalizumab therapy was tested in a 4-arm, double-blind, placebo-controlled study. Flow cytometry was used to detect serum inhibitory activity for IgE-facilitated CD23-dependent allergen binding to B cells as a surrogate marker for facilitated antigen presentation. Serum ragweed-specific IgG4 was measured by means of ELISA.Results Immunotherapy alone resulted in partial inhibition of allergen-IgE binding after 5 to 19 weeks of treatment compared with baseline (P < .01). Complete inhibition of allergen-specific IgE binding was observed in both treatment groups receiving omalizumab (P < .001). Allergen-specific IgG4 levels were only increased after immunotherapy (P < .05), both in the presence and absence of anti-IgE treatment. Combined treatment resulted in the induction of long-lasting inhibitory antibody function for up to 42 weeks compared with either treatment alone.Conclusion Ragweed immunotherapy induced serum regulatory antibodies that partially blocked binding of allergen-IgE complexes to B cells. Additional treatment with anti-IgE, by directly blocking IgE binding to CD23, completely inhibited allergen-IgE binding.Clinical implications The combination of ragweed immunotherapy and anti-IgE resulted in prolonged inhibition of allergen-IgE binding compared with either treatment alone, events that might contribute to enhanced efficacy.
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In vitro, combination therapy inhibited allergen-specific IgE binding for 42 weeks after discontinuation, compared with 30 weeks for omalizumab alone.
“An unrelated study by Klunker et al.1734 provides further evidence for the efficacy of combination therapy, with in vitro demonstration of inhibition of allergen-specific IgE binding for 42 weeks after discontinuation of combination therapy (vs 30 weeks with omalizumab alone).”
From International Consensus Statement on Allergy and Rhinology: Allergic Rhinitis (2018) · cites this paper as [1734]
Combination omalizumab and AIT decreases the incidence of AIT-associated systemic allergic reactions and improves control of AR symptoms.
“Two benefits of combination therapy have been described: decreased incidence of AIT-associated systemic allergic reactions and improved control of AR symptoms.1400-1402,1734-1736”
From International Consensus Statement on Allergy and Rhinology: Allergic Rhinitis (2018) · cites this paper as [1734]
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- Authors
- Klunker, S., Saggar, L. R., Seyfert-Margolis, V., Asare, A. L., Casale, T. B., Durham, S. R., & Francis, J. N.
- Affiliations
- Imperial College London (GB)
- Immune Tolerance Network (US)
- Creighton University (US)
- Corresponding author
- Francis, James N.
- Venue
- Journal of Allergy and Clinical Immunology
- Publisher
- Elsevier BV
- Published
- 2007-09
- Volume
- 120
- Issue
- 3
- Pages
- 688-695
- ISSN
- 0091-6749 (ISSN-L)
- OpenAlex
- W2033222579
- Cited by
- 129
- References
- 38
- Citations by year
- 2026: 1 · 2025: 2 · 2024: 6 · 2023: 6 · 2022: 5 · 2021: 5 · 2020: 4 · 2019: 10 · 2018: 5 · 2017: 4 · 2016: 7 · 2015: 10 · 2014: 12 · 2013: 3 · 2012: 10
- FWCI
- 6.02
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Journal of Allergy and Clinical Immunology (publishedVersion)
- PubMed (publishedVersion)
- Funders
- GlaxoSmithKline
- Immune Tolerance Network
- Allergy Therapeutics
- Genentech
- UCB Pharma
- Topics
- Health Sciences › Medicine › Immunology and Allergy › Allergic Rhinitis and Sensitization
- Health Sciences › Medicine › Immunology and Allergy › Food Allergy and Anaphylaxis Research
- Health Sciences › Medicine › Physiology › Asthma and respiratory diseases
- Keywords
- omalizumab, allergen immunotherapy, ragweed allergy, allergic rhinitis, anti-IgE therapy, CD23, IgG4, B cells, combination therapy
- MeSH terms
- Omalizumab, Adult, Antibodies, Anti-Idiotypic, Antibodies, Monoclonal, B-Lymphocytes, Combined Modality Therapy, Desensitization, Immunologic, Double-Blind Method, Flow Cytometry, Rhinitis, Allergic, Seasonal, Humans, Immunoglobulin E, Immunoglobulin Fab Fragments, Middle Aged, Antigen Presentation, Anti-Allergic Agents, Ambrosia, Antigens, Plant, Antibodies, Monoclonal, Humanized
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