Efficacy of combination treatment with anti-IgE plus specific immunotherapy in polysensitized children and adolescents with seasonal allergic rhinitis
Open accessAbstract
Background Specific immunotherapy (SIT) and treatment with monoclonal anti-IgE antibody have complementary modes of action.Objective The purpose of this study was to determine whether combined therapy could provide better efficacy than either treatment alone.Methods We conducted a randomized, double-blinded trial to assess the efficacy and safety of subcutaneously administered anti-IgE (omalizumab) or placebo in children and adolescents with seasonal allergic rhinitis in both a birch pollen season and a grass pollen season (sequential seasons together lasting an average of 84 days). There were 4 treatment arms. Each subject was started on SIT-birch or SIT-grass, and anti-IgE or placebo was started before and maintained during the anticipated pollen seasons (a total of 24 weeks). The primary efficacy variable was symptom load, the sum of daily symptom severity score plus rescue medication use.Results A total of 221 subjects (intent-to-treat population) aged 6 to 17 years were analyzed for efficacy. Combination therapy reduced symptom load over the 2 pollen seasons by 48% (P <.001) over SIT alone. When analyzed separately by season, the 2 groups receiving unrelated SIT were considered placebo controls. In the grass season, symptom loads were as follows: unrelated (birch) SIT + placebo, 0.89 (reference value); unrelated (birch) SIT + anti-IgE, 0.49 (-45%); SIT-grass + placebo, 0.61 (-32%); SIT-grass + anti-IgE, 0.26 (-71%).Conclusion Anti-IgE therapy conferred a protective effect independent of the type of allergen. Additional clinical benefit was demonstrated in both pollen seasons, whether there was coverage by SIT or not. This combination might prove useful for the treatment of allergic rhinitis, particularly for polysensitized patients.
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
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 [1400]
The Abstract reports that combination therapy reduced allergic-rhinitis symptom load by 48% compared with immunotherapy alone. The discussion describes a reduction in immunotherapy-induced systemic reactions only as a speculative possibility and says a study was planned to investigate it; the Safety section does not establish a decreased incidence. (LLM, conf=0.90)
Experimental — accuracy not yet measuredIn 221 adolescents with moderate-to-severe AR and birch and grass pollen sensitization, combination therapy was superior to AIT alone, with a 48% reduction in symptom load during an entire pollen season.
“Kuehr et al.1400 evaluated 221 adolescents (6 to 17 years) with moderate to severe AR and sensitization to birch and grass pollen. Using a randomized, controlled design, the effectiveness of combination therapy was evaluated during sequential birch and grass pollen seasons, with comparison of AIT +/− concurrent omalizumab. Significant findings included superiority of combination therapies vs AIT”
From International Consensus Statement on Allergy and Rhinology: Allergic Rhinitis (2018) · cites this paper as [1400]
The Methods (page unavailable) describe children and adolescents aged 6–17 with confirmed birch and grass pollen sensitization. The Efficacy section (page unavailable) reports a 48% lower median symptom load across the combined birch and grass seasons with SIT plus omalizumab than with SIT alone. Our copy does not establish that all 221 participants had moderate-to-severe rhinitis, and the study included children as well as adolescents. (LLM, conf=0.85)
Experimental — accuracy not yet measuredIn that trial, combination therapy reduced the median rescue medication score by 80% compared with AIT alone.
“and 80% reduction in median rescue medication score.”
From International Consensus Statement on Allergy and Rhinology: Allergic Rhinitis (2018) · cites this paper as [1400]
Experimental — accuracy not yet measured
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Cites
Long-Term Clinical Efficacy of Grass-Pollen Immunotherapy
Durham, S. R., Walker, S. M., Varga, E., Jacobson, M. R., O'Brien, F., Noble, W. J., Till, S. J., Hamid, Q. A., & Nouri‐Aria, K. T. (1999) · New England Journal of Medicine · doi:10.1056/nejm199908123410702 · Cited by 1,371 · see citing works
Solèr, M., Matz, J., Townley, R. G., Buhl, R., O'Brien, J., Fox, H., Thirlwell, J., Gupta, N., & Cioppa, G. D. (2001) · European Respiratory Journal · doi:10.1183/09031936.01.00092101 · Cited by 825 · see citing works
MacGlashan, D. W., Bochner, B. S., Adelman, D. C., Jardieu, P. M., Togias, A. G., McKenzie‐White, J., Sterbinsky, S. A., Hamilton, R. G., & Lichtenstein, L. M. (1997) · The Journal of Immunology · doi:10.4049/jimmunol.158.3.1438 · Cited by 821 · see citing works
Allergen Immunotherapy: Therapeutic Vaccines for Allergic Diseases
Bousquet, J., Lockey, R. F., Malling, H., Álvarez-Cuesta, E., Canonica, G. W., Chapman, M. D., Creticos, P. S., Dayer, J., Durham, S. R., Demoly, P. M., et al. (1998) · Annals of Allergy Asthma & Immunology · doi:10.1016/s1081-1206(10)63136-5 · Cited by 739 · see citing works
Fahy, J. V., Fleming, H., Wong, H. H., Liu, J. T., Su, J. Q., Reimann, J. D., Fick, R. B., & Boushey, H. A. (1997) · American Journal of Respiratory and Critical Care Medicine · doi:10.1164/ajrccm.155.6.9196082 · Cited by 712 · see citing works
Treatment of Allergic Asthma with Monoclonal Anti-IgE Antibody
Milgrom, H., Fick, R. B., Su, J. Q., Reimann, J. D., Bush, R. K., Watrous, M. L., & Metzger, W. J. (1999) · New England Journal of Medicine · doi:10.1056/nejm199912233412603 · Cited by 703 · see citing works
Sublingual immunotherapy for allergic rhinitis
Wilson, D. R., Lima, M. T., & Durham, S. R. (2003) · Cochrane Database of Systematic Reviews · doi:10.1002/14651858.cd002893 · Cited by 477 · see citing works
Inhibitory Effects of an Anti-IgE Antibody E25 on Allergen-Induced Early Asthmatic Response
Boulet, L., Chapman, K. R., Côté, J., Kalra, S., Bhagat, R., Swystun, V. A., Laviolette, M., Cleland, L. D., Deschesnes, F., Su, J. Q., et al. (1997) · American Journal of Respiratory and Critical Care Medicine · doi:10.1164/ajrccm.155.6.9196083 · Cited by 399 · see citing works
A Controlled Trial of Immunotherapy for Asthma in Allergic Children
Adkinson, N. F., Eggleston, P. A., Eney, D., Goldstein, E. O., Schuberth, K. C., Bacon, J. R., Hamilton, R. G., Weiss, M. E., Arshad, H., Meinert, C. L., et al. (1997) · New England Journal of Medicine · doi:10.1056/nejm199701303360502 · Cited by 341 · see citing works
Recombinant humanized mAb-E25, an anti-IgE mAb, in birch pollen–induced seasonal allergic rhinitis
Adelroth, E. C., Rak, S., Haahtela, T., Aasand, G., Rosenhall, L., ZETTERSTRÖM, O., Byrne, A., Champain, K., Thirlwell, J., Cioppa, G. D., et al. (2000) · Journal of Allergy and Clinical Immunology · doi:10.1067/mai.2000.108310 · Cited by 315 · see citing works
TREATMENT OF ALLERGIC ASTHMA WITH MONOCLONAL ANTI-IgE ANTIBODY
Ilgrom, H. E. M., Ick, R. O. B. F., Ohn, J., Eimann, J. A. D. R., Ush, R. O. K. B., Arc, M., Atrous, L. W., Ames, W. J., & Roup, S. T. G. (1999) · Cited by 281 · see citing works
Grass pollen immunotherapy: efficacy and safety during a 4‐year follow‐up study
Walker, S. M., Varney, V., Gaga, M., Jacobson, M. R., & Durham, S. R. (1995) · Allergy · doi:10.1111/j.1398-9995.1995.tb01170.x · Cited by 151 · see citing works
Bousquet, J., Becker, W., Hejjaoui, A., Chanal, I., Lebel, B., Dhivert, H., & Michel, F. B. (1991) · Journal of Allergy and Clinical Immunology · doi:10.1016/0091-6749(91)90299-4 · Cited by 148 · see citing works
Simpson, B. M., Custovic, A., Simpson, A., Hallam, C. L., Walsh, D., Marolia, H., Campbell, J., & Woodcock, A. (2001) · Clinical & Experimental Allergy · doi:10.1046/j.1365-2222.2001.01050.x · Cited by 134 · see citing works
White, Smith, H. E., Baker, B. I., Davis, & Frew (1998) · Clinical & Experimental Allergy · doi:10.1046/j.1365-2222.1998.00237.x · Cited by 109 · see citing works
Practice parameters for allergen immunotherapy
Nicklas, R. A., Bernstein, I. L., Blessing-Moore, J., Fìneman, S. M., GUTMAN, A., Lee, R. E., LI, J., Berger, W. E., Spector, S. L., Bernstein, I. L., et al. (1996) · Journal of Allergy and Clinical Immunology · doi:10.1016/s0091-6749(96)80183-7 · Cited by 85 · see citing works
Bousquet, J., Hejjaoui, A., Becker, W. M., et al. (1991) · Journal of Allergy and Clinical Immunology · doi:10.1016/0091-6749(91)90397-7 · Cited by 63 · see citing works
Immunotherapy: Past and present
Norman, P. S. (1998) · Journal of Allergy and Clinical Immunology · doi:10.1016/s0091-6749(98)70046-6 · Cited by 58 · see citing works
Is There a Role for Immunotherapy in the Treatment of Asthma? Yes
Norman, P. S. (1996) · American Journal of Respiratory and Critical Care Medicine · doi:10.1164/ajrccm.154.5.8912729 · Cited by 53 · see citing works
Risk management in allergen immunotherapy
Greineder, D. K. (1996) · Journal of Allergy and Clinical Immunology · doi:10.1016/s0091-6749(96)80119-9 · Cited by 41 · see citing works
Immunotherapy for Allergic Rhinitis
Adkinson, N. F. (1999) · New England Journal of Medicine · doi:10.1056/nejm199908123410710 · Cited by 27 · see citing works
Flagged first, then by citations
Cited by
Sorted by citations
Allergic Rhinitis and its Impact on Asthma (ARIA) 2008*
Bousquet, J., Khaltaev, N., Cruz, A. A., Denburg, J., Fokkens, W. J., Togias, A., Zuberbier, T., Baena‐Cagnani, C. E., Canonica, G. W., Van Weel, C., et al. (2008) · Allergy · doi:10.1111/j.1398-9995.2007.01620.x · Cited by 4,729 · see citing works
Allergic Rhinitis and its Impact on Asthma (ARIA) guidelines: 2010 Revision
Brożek, J. L., Bousquet, J., Baena-Cagnani, C. E., Bonini, S., Canonica, G. W., Casale, T. B., van Wijk, R. G., Ohta, K., Zuberbier, T., & Schünemann, H. J. (2010) · Journal of Allergy and Clinical Immunology · doi:10.1016/j.jaci.2010.06.047 · Cited by 1,813 · see citing works
Allergen immunotherapy: A practice parameter third update
Cox, L., Nelson, H., Lockey, R., Calabria, C., Chacko, T., Finegold, I., Nelson, M., Weber, R., Bernstein, D. I., Blessing-Moore, J., et al. (2011) · Journal of Allergy and Clinical Immunology · doi:10.1016/j.jaci.2010.09.034 · Cited by 1,256 · see citing works
International Consensus Statement on Allergy and Rhinology: Allergic Rhinitis
Wise, S. K., Lin, S. Y., Toskala, E., Orlandi, R. R., Akdis, C. A., Alt, J. A., Azar, A., Baroody, F. M., Bachert, C., Canonica, G. W., et al. (2018) · International Forum of Allergy & Rhinology · doi:10.1002/alr.22073 · Cited by 557 · see citing works
Casale, T. B., Busse, W. W., Kline, J. N., Ballas, Z. K., Moss, M. H., Townley, R. G., Mokhtarani, M., Seyfert-Margolis, V., Asare, A., Bateman, K., et al. (2006) · Journal of Allergy and Clinical Immunology · doi:10.1016/j.jaci.2005.09.036 · Cited by 355 · see citing works
Massanari, M., Nelson, H., Casale, T., Busse, W., Kianifard, F., Geba, G. P., & Zeldin, R. K. (2010) · Journal of Allergy and Clinical Immunology · doi:10.1016/j.jaci.2009.11.022 · Cited by 230 · see citing works
Kopp, M. V., Hamelmann, E., Zielen, S., Kamin, W., Bergmann, K. ‐., Sieder, C., Stenglein, S., Seyfried, S., Wahn, U., & for the DUAL study group (2009) · Clinical & Experimental Allergy · doi:10.1111/j.1365-2222.2008.03121.x · Cited by 181 · see citing works
Self-citationRolinck‐Werninghaus, C., Hamelmann, E., Keil, T., Kulig, M., Koetz, K., Gerstner, B., Kuehr, J., Zielen, S., Schauer, U., Kamin, W., et al. (2004) · Allergy · doi:10.1111/j.1398-9995.2004.00552.x · Cited by 120 · see citing works
Self-citationKopp, M. V., Brauburger, J., Riedinger, F., Beischer a, D., Ihorst, G., Kamin, W., Zielen, S., Bez, C., Friedrichs, F., von Berg, A., et al. (2002) · Journal of Allergy and Clinical Immunology · doi:10.1067/mai.2002.128804 · Cited by 84 · see citing works
Self-citationMast Cells in Allergic Airway Disease and Chronic Rhinosinusitis
Pawankar, R. (2005) · Chemical Immunology and Allergy · doi:10.1159/000087639 · Cited by 59 · see citing works
Management of asthma with anti-immunoglobulin E: A review of clinical trials of omalizumab
Nowak, D. (2006) · Respiratory Medicine · doi:10.1016/j.rmed.2005.10.004 · Cited by 59 · see citing works
Is there a role for anti-IgE in combination with specific allergen immunotherapy?
Hamelmann, E., Rolinck-Werninghaus, C., & Wahn, U. (2003) · Current Opinion in Allergy and Clinical Immunology · doi:10.1097/00130832-200312000-00013 · Cited by 25 · see citing works
Self-citation
- Authors
- Kuehr, J., Brauburger, J., Zielen, S., Schauer, U., Kamin, W., Von Berg, A., Leupold, W., Bergmann, K.-C., Rolinck-Werninghaus, C., Gräve, M., Hultsch, T., & Wahn, U.
- Affiliations
- University of Freiburg (DE)
- Novartis (Germany) (DE)
- University of Bonn (DE)
- Johannes Gutenberg University Mainz (DE)
- Auguste-Viktoria-Klinik (DE)
- Novartis (Switzerland) (CH)
- Venue
- Journal of Allergy and Clinical Immunology
- Publisher
- Elsevier BV
- Published
- 2002-02
- Volume
- 109
- Issue
- 2
- Pages
- 274-280
- ISSN
- 0091-6749 (ISSN-L)
- OpenAlex
- W2162051917
- Cited by
- 342
- References
- 21
- Citations by year
- 2026: 7 · 2025: 7 · 2024: 8 · 2023: 11 · 2022: 14 · 2021: 14 · 2020: 9 · 2019: 11 · 2018: 9 · 2017: 8 · 2016: 14 · 2015: 14 · 2014: 18 · 2013: 15 · 2012: 16
- FWCI
- 9.98
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Journal of Allergy and Clinical Immunology (publishedVersion)
- PubMed (publishedVersion)
- FreiDok plus (Universitätsbibliothek Freiburg) (submittedVersion)
- 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, anti-IgE therapy, allergen immunotherapy, allergic rhinitis, polysensitized patients, combination therapy, birch pollen allergy, grass pollen allergy, children and adolescents, symptom burden, rescue medication use
- MeSH terms
- Omalizumab, Adolescent, Antibodies, Anti-Idiotypic, Antibodies, Monoclonal, Child, Combined Modality Therapy, Desensitization, Immunologic, Double-Blind Method, Female, Poaceae, Rhinitis, Allergic, Seasonal, Humans, Immunoglobulin E, Male, Pollen, Treatment Outcome, Anti-Allergic Agents, Betula, Antibodies, Monoclonal, Humanized
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
